The inequality between rich and poor nations in the treatment of HIVinfected people not only represents a moral scandal but has become a major economic political and social challenge that threatens world’s stability. A number of experts have assessed the obstacles to a faster access to treatment in the developing world and, for some, have advocated to favor prevention over treatment.
When highly active antiretroviral therapy (HAART) first became available in 1996, it represented the last hope for many thousands of people with a fatal disease. Compared to the threat of AIDS, side effects, as far as they were known at the time, appeared insignificant. Given the lack of alternative treatment in case of resistance the quest for primary efficacy dominated: your first chance was your only chance.
Several issues need to be considered when deciding whether to initiate therapy in a person with asymptomatic HIV infection. Concerns with delaying therapy have included: the risk of development of an AIDS defining disease; the possibility that the rate of virological failure (with its resistance-related consequences for future treatment options) is higher in those with higher viral load and/or lower CD4 count prior to therapy, and hence will increase with a delay; the possibility that there may be some irretrievable loss of immune capacity.
This session will discuss my diagnosis and the consequent evolution. Broadly this will include medical history (gastro-intestinal problems, hepatitis, etc.); virological situation today; most prominent personal fears and anxieties of starting therapy.
Although continuous HAART has resulted in a decrease in the mortality and morbidity rates associated with HIV infection in western countries, the utility of therapy is dampened by suboptimal activity, excess in toxicity, and inconvenience. Among 667 untreated patients from the Swiss HIV cohort, 126 had discontinued therapy as a consequence of treatment limitations.
Antiretroviral therapy changes the natural history of HIV infection, and this has resulted in dramatic improvements in HIV-related morbidity and mortality throughout the developed world. However, despite the current availability of 16 antiretroviral drugs approved for the treatment of HIV infection, current combination regimens have limitations.
Robert Murphy1, Alexandra Thiry, Marco Mancini2, Vadim Pokrovsky3, Willy Rozenbaum4
Atazanavir (ATV) is a potent, safe, and effective once-daily PI in phase III development. In BMS trial AI424-008, ATV demonstrated a lipid profile superior to nelfinavir (NFV) in treatment-naïve subjects. The objectives of BMS AI424-044 were to evaluate lipid profiles of subjects switched from NFV to ATV as well as ATV safety and tolerability.
Martin King, Kathryn Real, Scott Brun1Luc Perrin, Sabine Yerly2
Lopinavir (LPV), an HIV protease inhibitor, is co-formulated with ritonavir (r), which inhibits cytochrome p450 3A4, providing increased plasma levels of LPV. Long-term clinical trials of LPV/r in HIV-infected pts are ongoing.
Andrew Leigh Brown1, Simon Frost, Christopher Mathews, Douglas Richman, Susan Little2, Eric Daar3, Nicholas Hellmann4,
Effective combination therapy can reduce HIV transmission but the benefits are reduced by the selection and transmission of drug resistant strains. We analyzed treatment rates, response to antiretroviral (ARV) therapy and transmission of ARV-resistant HIV in San Diego from 1997 onwards, using an empirical epidemiological model to obtain projections of future trends.
SESSION 4:
ANTIVIRAL THERAPY IN RESOURCE POOR SETTINGS (ORGANISED BY THE INTERNATIONAL AIDS SOCIETY [IAS])
By the end of year 2001, it was estimated that 40 million people worldwide were infected with HIV. Over 80% reside in the resource-poor settings of which 28.5M are in sub-Saharan Africa. Since 1995 morbidity and mortality related to HIV-infection has been dramatically decreased in the developed world due to the use of antiretroviral drugs.
The World Health Organization (WHO) estimates that today, 6 million HIV-infected people in resource-poor settings are in immediate need of highly active antiretroviral treatment (HAART). However, only 230.000 are actually receiving the medicines and just 25.000 of them are living in sub-Saharan Africa.
Ernest Darkoh-Ampem, G Obita, D De Korte, P Mazonde
Botswana, with a relatively small population of 1.6-1.7 million, is in the unenviable situation of having the highest adult prevalence of HIV in the world (estimated 38.5% of the 15-49 age group). The Government of Botswana (GOB) therefore decided to provide anti-retroviral drugs (ARV Therapy) to all eligible citizens through the public health system to avoid human and economic losses of a devastating and unacceptable magnitude.
One of the most important clinical developments in the treatment of HIV infected patients in recent years is our understanding of the truly crucial significance adherence plays in the success of HAART. Although our initial efforts in implicating combination antiretroviral therapy focused almost entirely on the pharmacological and virological aspects of the compounds – we have now learned that drug taking behavior is perhaps the single most important element in the successful management of HIV infection.
Failure to achieve complete viral suppression by antiretroviral treatment is common in clinical practice, occurring at a high rate in many cohorts. The reasons for drug failure are multi-factorial but resistance to current medications is recognized to be an important element.
A Mocroft1, A Phillips, P Reiss, B Clotet, B Ledergerber, J Gatell, C Katlama, S Vella, N Clumeck, J D Lundgren2
The aims of this study were to determine the rate of virological rebound and factors associated with rebound among patients who initially responded to HAART by achieving undetectable levels of viraemia. Patients were followed from the date of initial undetectable viral load (<400, <200 or <50 copies/ ml), providing this occurred within 12 months of starting HAART, to the first of 2 consecutive viral loads above this level, or the date of last viral load measure.
L Bacheler1, H van Marck, T Maguire, T Van Den Bulcke, M P de Béthune, P LeCocq2
The VirtualPhenotype™. is an HIV-1 resistance analysis tool that provides a quantitative, data-driven assessment of drug susceptibility for all currently approved HIV antivirals based on viral genotype. The basis of this analysis is a large dataset (G/P dataset, currently >28,000) of HIV-1 clinical isolate genotypes and matching drug susceptibility phenotypes.
Animal studies have indicated that it is possible to abort HIV infection through the use of antiretroviral agents. Moreover, studies of mother-to-child transmission suggest that a substantial proportion of the benefits of antiretroviral therapy actually reflects post-exposure prophylaxis (PEP) provided to the neonate.
Franco Maggiolo, Annapaola Callegaro, Diego Ripamonti, Giampietro Gregis, Gianpaolo Quinzan, Claudio Arici, Laura Ravasio, Fredy Suter
Well tolerated compact regimens may limit the drawbacks of HAART due to the complexity of daily dosing schedule and to the occurrence of metabolic adverse events.
Nicola Gianotti, Alessandro Soria, Laura Galli, Daniela Vacchini, Massimo Cernuschi, Adriano Lazzarin
Treatment interruption (TI) in HIV-1 infected patients with virologic failure may lead to a shift from a drug-resistant to a wild-type predominant viral population in plasma. However, long-term response to re-initiation of therapy has not been reported. The objective of this study was to assess if a long-term virologic response could be achieved in this setting.
R Murri, A Cozzi Lepri, AP Phillips, E Girardi, G Nasti, S Ferrara, MS Mura, C Mussini, E Petrelli, M Arlotti, C De Stefano, P Vigano, L Gennero, B Salassa, G Antonucci, P Narciso, S Chigiotti, T Prestileo, R Novati, R Cargnel1, A D'arminio Monforte2
Possible differences between men and women in the natural history and in the clinical management of HIV infection have been described but with conflicting results. To assess the differences between genders in the likelihood of starting antiretroviral therapy (ART), in rates of sustained discontinuations from highly active antiretroviral therapy (HAART), and to establish whether a gender difference in survival exists.
On the basis of the recent advances in the characterization of HIV-1-specific CD4 and CD8 T cell immune responses, it is clear that the type of the immune abnormalities associated with HIV-1 infection are both quantitative and qualitative.
The investigation of novel and innovative treatment approaches for long-term management of HIV-infection has intensified due to the growing number of infected individuals worldwide and the constraints of resistance, toxicity and convenience associated with lifelong therapy. Current treatment relies entirely on antiretroviral drugs targeting various stages of the life cycle of HIV, rather than on leveraging the immune system.
Susan Hopkins, Gillian Farrell, Fiona Lyons, Fiona Mulcahy, Colm Bergin
Morbidity and mortality related to HIV infection has significantly decreased due to the introduction of highly active antiretroviral therapy (HAART). However, morbidity associated with Hepatitis C (HCV) is increasingly affecting the HIV/HCV co-infected cohort.
Krishnan Bhaskaran, on behalf of CASCADE collaboration
Following the introduction of potent antiretroviral therapy in the mid-1990s, the incidence of non-Hodgkin lymphoma (NHL) did not appear to drop as dramatically as other AIDS diseases. We aimed to investigate whether the risk of NHL has changed more recently, and to assess the importance of current and nadir CD4 cell count and other prognostic factors in predicting an NHL diagnosis, thus determining whether early initiation of therapy may be warranted in certain groups.
The use of therapeutic drug monitoring (TDM) has received an increasing amount of interest during the last years. Some national guidelines (e.g. France, United Kingdom, The Netherlands) have now included TDM as part of diagnostic set up for a patient, but development of TDM in other countries still in its infancy.
Patrick Hoggard, Emma Meaden, John Tjia David Back, Saye Khoo, Phillippa Newton, Ian Williams, David Cornforth, Diane Aldam
HIV protease inhibitors (PIs) are substrates for the drug efflux transporters P-glycoprotein and multidrug resistance-associated protein. Inter-individual variation in the expression of these two transporters may therefore affect intracellular PI accumulation in vivo
Jennifer Ford, Rhiannon Meaden, Patrick Hoggard, Saye Khoo, David Back
Increased expression of the efflux transporters P-glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP1) has been suggested as a potential mechanism for decreased protease inhibitor (PI) availability at certain intracellular sites, providing sanctuary for HIV.
Jacques Grassi, François Becher, Alain Pruvost, Dimitri Schlemmer, Christophe Créminon, Henri Benech, Cécile Goujard, Jean-François Delfraissy
Nucleoside reverse transcriptase inhibitors (NRTIs) are anabolised intracellularly to their known corresponding active triphosphate (TP). This intracellular anabolism plays a critical role regarding both their efficacy and toxicity.
JA Gogtay, V Manek, VG Nayak, PV Bodhe1, A Dasgupta, V Srivatsan, G Vaidyanathan, KC Patel2
The most important factor determining virologic success in HIV therapy is patient adherence. In the last few years efforts have being made to improve adherence by the introduction of newer agents with reduced frequency of pill administration and fixed dose combination products. One such product introduced was Trizivr, which contains 3 NRTIs viz. zidovudine, lamivudine and abacavir.
HIV infection itself induces multiple metabolic abnormalities: e.g. increases in resting energy expenditure and lipolysis, while glucose metabolism is characterized by increased insulin sensitivity. Combination antiretroviral therapy including protease inhibitors for the treatment of HIV-1-infected patients has been associated with the development of a fat redistribution syndrome, which may include both central fat accumulation and peripheral fat wasting.
Whether anti-HIV drugs accelerate the atherosclerotic process and thereby enhances the risk of coronary heart disease (CHD) and stroke remains a controversial question. Drugs from all three classes may increase the plasma concentration of cholesterol, LDL-cholesterol and triglycerides.
Lipodystrophy (LD; peripheral lipoatrophy, central fat accumulation, and lipomatosis) is a common, disfiguring but ill-defined problem in HIV-infected patients receiving antiretroviral therapy that is associated with sub-optimal antiretroviral adherence.
In Europe, it is estimated that approximately 30% of HIV-infected individuals are coinfected with HCV. HCV coinfection is even higher (50% to 90%) among high risk groups such as intravenous drug users and hemophiliacs.
Hepatitis B virus (HBV) infection is common in HIV-positive individuals, due to shared routes of transmission of both viruses. Chronic HBV infection (as defined by positivity for serum HBsAg) affects overall 8% of HIV-positive persons in western countries. As HBV causes liver damage through an immune-mediated mechanism, the immunodeficiency produced by HIV is associated with a reduction in aminotransferase levels despite an enhancement in HBV replication.
Vaccination is an excellent and easy way to protect individuals against a variety of infectious diseases. Whether vaccination is beneficial for the individual depends on the incidence of the relevant disease, the rate of protection induced by the vaccine and the potential side effects of the vaccination.
Advances in the management of HIV in pregnancy have lead to large reductions in the mother-to-child transmission (MTCT) rate in countries where these interventions are accessible. Clinical trials and a number of observational studies have shown that overall rates can be reduced to below 2%.
Tolerance of perinatal antiretroviral prophylaxis remains to be assessed on a large scale and in the long term. The possibility of mitochondrial toxicity remains contested.
In England, recent increases in the rates of sexually transmitted infections (STI), coupled with the emerging outbreaks of infectious syphilis, have drawn attention to the need for improving the sexual health of HIVpositive individuals.
C Pradier, E Fontas1, C Sabin2, N Friis-Møller, JD Lundgren for the D:A:D study group3, R Weber4, P Reiss5, A d'Arminio Monforte6, O Kirk7, R Thiebaut8, L Morfeldt9, G Calvo10, M Law11, G Bartsch12, S De Wit13
To compare the impact of the various individual PIs and PI combinations on dyslipidaemia. Baseline risk factors for the development of cardiovascular disease (CVD) were collected on 17,852 HIV-patients from Europe, USA and Australia, enrolled in DAD, a prospective cohort study assessing risk of CVD, established in year 2000.
Luis Caldeira1, Celia Carvalho1, Emilia Valadas1, Luis Tavares1, Alexandra Zagalo e Melo1, Alvaro Pereira1, Nelson Duarte1, Alice Ribeiro1, Nidia Garrido1, Patricia Pacheco1, Francisco Antunes1, João Cruz2, Pedro Aguiar3
Antiretroviral compounds from the NNRTI group have been associated with the occurrence of hepatic toxicity. However, large studies evaluating the comparative incidence of liver toxicity of nevirapine and efavirenz, especially in the subset of patients with HBV and/or HCV co-infection, are scarce and contraditory.
Graeme Moyle1, Eric Daar2, Joseph Gertner3, Donald Kotler4, Jean-Claude Melchior5, Fanny O'brien3, Elisabeth Svanberg6
Wasting with lean body mass (LBM) loss is a major complication in AIDS. Although prevalence has fallen, wasting remains a chronic debilitating, life-threatening condition.
Recent years have seen an increased risk of bone problems emerge as a potential long-term problem for HIV-infected individuals. Two issues in particular seem to be relevant and different: an apparent increased rate of osteonecrosis and an apparent increased risk of developing osteopenia and osteoporosis.
NRTIs act as false nucleoside substrates for Polymerase-g, which mediates mitochondrial DNA synthesis, and this may result in NRTI-related DNA depletion and clinical manifestations of mitochondrial dysfunction.
Experts in drug safety monitoring from the academic, government, and industry sectors held a workshop with research clinicians specializing in HIV in April of this year to review the relevance of ‘standard’ monitoring procedures for long-term drug safety to HIV.
S López, Ò Miró, F Cardellach, A Beato, J Casademont1, M Garcia, E Martínez, A Milinkovic, Jl Blanco2, A Soler, E Pedrol3
Nucleoside reverse transcriptase inhibitors (NRTIs) are being increasingly associated with mitochondrial (MT) toxicity. We aimed to assess MT content and function in peripheral blood mononuclear cells (PBMCs) of HIV-infected patients previous to the development of clinically evident body fat changes.
Ò Miró, S López, E Martínez, F Cardellach, J Casademont, J M Gatell1, E Pedrol, A Soler2, B Rodríguez-Santiago, V Nunes3
To simultaneously evaluate mitochondrial DNA (mtDNA) content and mitochondrial respiratory chain (MRC) function in peripheral lymphocytes of HIV-infected patients who had developed lipodystrophy (LD) while on highly active antiretroviral therapy (HAART).
Anna-Maria Bauer, Johannes Bogner, Sophia Horster, Mirjam Schunk, Thomas Sternfeld, Frank-D Goebel
Prognosis of lactic acid (LA) increase is still uncertain. While asymptomatic elevation is thought to be of little significance, lactic acidosis still has a high mortality. Our objective was to determine kinetics of LA in order to test whether the metabolic capacity of lactate degradation is influenced by HAART and baseline LA levels.
Joep Lange1, A Lazzarin2, B Clotet3, D Cooper4, J Reynes5, K Arasteh6, M Nelson7, C Katlama8, H-J Stellbrink9, J-F Delfraissy10, J Chung, M Salgo, on Behalf of The TORO 2 Study Group11, R Demasi, J Delehanty12
Enfuvirtide (T-20; ENF) is the first in a new class of HIV antiretrovirals, the fusion inhibitors, which targets HIV gp41 and blocks the virus from entering the host cells. The phase III study TORO 2 (T-20 vs Optimized Regimen Only) was conducted in Europe and Australia. Patients with ≥ 3 months prior experience with three classes of ARVs, and HIV-1 RNA ≥ 5,000 copies/mL selected an optimized background (OB) regimen of three to five ARVs based on prior history and BL genotypic and phenotypic viral resistance.
D Schürmann1, J Gathe2, I Sanne3, R Wood4 on behalf of the SOLO Study Team
GW433908 (908) is a new protease inhibitor, with a well characterised distinct resistance profile, and the potential for once daily dosing (QD) when combined with low dose ritonavir (RTV). SOLO is a randomised, open-label study in ART-naïve subjects comparing the efficacy and safety of 908/RTV QD vs nelfinavir (NFV) BID over 48 weeks.
Ulrik Bak Dragsted1, J Gerstoft2, M Youle2, A Duran2, D TJayaweera2, A Rieger2,J NBruun2, A Castagna2, SWalmsley2, Z Fox2, A Hill2, J D Lundgren1,2
Few comparative data exists on the efficacy and safety of ritonavir(r)-boosted protease inhibitor regimens in the average HIV-1 infected population seen in out-patients’ clinics.
Anton Pozniak1, Schlomo Staszewski2, Joel Gallant3, Jamal Suleiman4, Edwin DeJesus5, Adriano Lazzarin6, San Tran, Biao Lu, Andrew Cheng, Dion Coakley7
TDF is a single tablet, once daily nucleotide analogue reverse transcriptase inhibitor with potent activity against wild-type and nucleoside resistant HIV. Prior studies have demonstrated significant and sustained anti- HIV activity when TDF was added to stable background ART in treatmentexperienced patients.
Ana Barrios, Teresa García-Benayas, Carmen De Mendoza1, Miriam Garrote, Luz Martín-Carbonero, Angélica Corral, Vincent Soriano1, Pere Domingo2, M José Galindo3, Juan Gálvez4, Vicente Estrada5, David Dalmau6, Víctor Asensi7
Tenofovir disoproxil fumarate (TDF), the first approved nucleotide analog (NtRTI), has shown a potent antiviral effect (mean reduction in plasma HIVRNA of 0.6 logs in pretreated patients) in clinical trials. TDF potency seems to be compromised when nucleoside-associated mutations (NAMs) are present, particularly 41L and/or 210W.
B Kearney, S Liaw, K Yale, S Hayashi, H Namini, J Wolf, D Coakley, J Flaherty
Tenofovir is eliminated by the kidney by both glomerular filtration and active tubular secretion. The pharmacokinetics (PK) of tenofovir are expected to be altered in subjects with clinically significant renal insufficiency.
Kit Simpson, E Chumney1, Michelle Luo, Barry Bernstein, Eugene Sun, Talat Ashraf2
Selecting the optimal treatment regimen for antiretroviral (ARV)-naïve patients may be difficult, given the concern about the antiviral activity, the development of drug resistance and the increase in drug costs. This study was undertaken to evaluate the costs and effectiveness of using lopinavir/ritonavir (LVP/r) vs. nelfinavir (NFV) as the first HAART regimen in treating HIV patients, based on the results from the recently published clinical trial ABTM98- 863.
D Bánhegyi, Z Gerlei, J Szlávik, Z Jánosi, E Ujhelyi
The ABT-378/r European Early Access Program was initiated in Hungary in November 2000 and between this date and December 2001 22 patients (pts), heavily pretreated with antiretrovirals (ARs) limited treatments options with viral failure were included.
Beatriz Díaz, Luz Martín-Carbonero, Carmen de Mendoza, Vicenç Soriano1, Pere Domingo2, María de los Angeles Lozano, María Jesús Téllez3, Jose Carmena4, Jose Sanz-Moreno5, María Leyes6
The aim of this research is to study treatment with Lopinavir in patients outside clinical trials and having failed on drugs from all classes.
J L Andrade Neto1, A Soto2, E Sprinz3, S Green4, M P Luo, R Rode, R L Tressler for the M00-267 Study Group5
A significant number of virologically stable, HIV-infected subjects experience mild-to-moderate side effects (SEs) related to the NNRTI or PI in their antiretroviral (ARV) regimen. Lopinavir/ritonavir (LPV/r) is generally well tolerated, and has demonstrated durable virologic suppression. However, it is unclear whether substituting LPV/r for the NNRTI/PI will alleviate the SEs and improve quality of life (QOL).
Mona Loutfy1, Courtney Thompson, Colin Kovacs, Anita Rachlis, Sharon Walmsley2, John Goodhew, Gary Rubin3
Current research efforts are focused on simplifying drug regimens to improve adherence and quality of life. Simplification strategies have included replacing the protease inhibitor (PI) component with lopinavir/ritonavir (LPV/r). We previously noted that such patients (pts) had an increase in their CD4c cell count. The purpose of the present study is to determine whether the CD4c increase was related to the LPV/r or was it a function of a pts’ improving immune status prior to the switch.
Michelle Luo, Robert Boggs, Barry Bernstein, Eugene Sun, Talat Ashraf
The ABT-M98-863 trial (double blinded, randomized) compared clinical outcomes of lopinavir/ritonavir (LVP/r) vs nelfinavir (NFV) plus d4T/3TC in 653 antiretroviral (ARV) naïve subjects.
Alan Landay1, John Spritzler2, Harold Kessler1, Donna Mildvan3, Minya Pu2, Lawrence Fox4, Daniel Kuritzkes5, Michael Lederman6
There still is substantial controversy in the field as to whether PI containing regimens offer a selective advantage over NRTI containing regimens regarding their level of functional immune reconstitution.
S Staszewski, B Dauer, P Gute, A Carlebach, A Haberl, S Klauke, M Mösch1, A N Phillips2
Based on data from controlled clinical trials, there is some concern about the activity of abacavir/zidovudine/lamivudine (ABC/AZT/3TC) in therapynaïve patients with a baseline viral load greater than 100,000 copies/ml.
Nelfinavir (NFV) and indinavir (IDV) are the most prescribed PIs. IDV combined with ritonavir (RTV) 100 mg bid is usually prescribed at the dose of 800 mg bid but recent pharmacokinetic data have shown that IDV 400 mg bid presents a good PK profile and provides a better tolerance.
The purpose of this study was 1) to follow changing trends in starting antiretroviral therapy (ART) between 1995 and 2001, 2) to evaluate sustainability of the initial ART over time, 3) to determine reasons for stopping/changing initial ART and 4) to compare PI- vs NNRTI-based therapy.
R A Seaton, R Fox, N Bodasing, S Peters, Y Gourlay
There are few data describing the use of co-formulated zidovudine, lamivudine and abacavir (Trizivir) in patients with AIDS. There has been concern that such therapy may be sub-optimal for patients with advanced disease.
To relate the outcome of our treatment model to outstanding problems in treated and treatment naïve patients and as a basis for discussion on allocation of resources for further improvement.
To determine the efficacy and tolerance of saquinavir (SQV) 3,600mg/d plus two nucleoside analogues in the treatment of naïve HIV-positive patients at 24 months.
To determine the efficacy and tolerance of saquinavir 1,800mg/d for intensifying the response of two nucleoside analogues in the treatment of non-naïve HIV-positive patients at four years.
George Chrysos, Androula Pastelli, Anastasios Visvikis, Stamatina Anagnostopoulou, George Lepeniotis, Panagiota Spyropoulou, Maria Dimou, Maria Papanocolaou
Highly Active AntiRetroviral Therapy (HAART) has dramatically reduced morbidity and mortality in HIV infected patients. However, with increasing concerns about toxicity and adherence, structured treatment interruption (STI) trials are not uncommon since STI may boost anti-HIV specific immunity.
A 49-year-old Zairian woman presented with a seven day history of headache, fever, lower back pain and general malaise 14 days after stopping her antiretrovirals (indinavir 800mg bd, ritonavir 100mg bd, lamivudine 150mg bd, zidovudine 300mg bd) at the start of a drug holiday.
Jan Gerstoft1, Ulrik Bak Dragsted2, Pedro Cahn3, Antonella Castagna4, Adriana Duran5, Andrew Hill6, Court Pedersen7, Barry Peters8, Pietro Vernazza9, Mike Youle10, Jens D. Lundgren on behalf of the MaxCmin1 Trial Group 2
Previous studies have claimed superiority of a ritonavir (r)-boosted protease inhibitor (PI) regimen. However, only a head-to-head comparison - of which this is the first - can reliably assess possible differences in r-boosted PI regimens.
Jean-Guy Baril1, Benoit Trottier2, Roger Leblanc3, Jim Lin4
Limited experience exists for once daily SQV 1600 mg plus RTV 100 or 200 mg (SQVr QD) based regimen as switch therapy especially in patients who have prior antiretroviral therapy (ART) failure.
Remko Van Leeuwen, on behalf of the 2NN Study Group
Nevirapine (NVP) and efavirenz (EFV) are non- nucleoside reverse transcriptase inhibitors (NNRTIs) that have demonstrated potency, safety, and convenience in separate clinical trials. As a result, they are frequently used as the basis of highly active antiretroviral therapy (HAART) for management of treatment-naïve patients.
Jean-Francois Delfraissy1, Antonio Rivero2, Alexey Yakovlev3, Kathleen Squires4, Alexandra Thiry, Michael Giordano, for the AI424-034 International Study Team5
Atazanavir (ATV) is a potent, safe, once-daily PI that has a distinct resistance profile, rapidly suppresses HIV RNA, increases CD4 cells, and provides superior lipid profile to other PIs. Efavirenz (EFV), a potent, once-daily NNRTI, is a standard of care in antiretroviral (ARV)-naïve patients.
A Holmes, F McGlynn, L McCullagh, S Hopkins, F Mulcahy
Treatment simplification to AZT/ 3TC/ ABC has been shown to maintain efficacy and improve metabolic parameters in several trials. Lower pill burden is postulated to increase the likelihood of adherence.
Franco Maggiolo, Claudio Arici, Laura Ravasio, Annapaola Callegaro, Giampietro Gregis, Gianpaolo Quinzan, Diego Ripamonti, Fredy Suter
Well tolerated compact regimens are required to overcome the drawbacks of HAART and its limits due to the complexity of daily dosing schedule and to the occurrence of metabolic adverse events.
Alain Lafeuillade, Patrick Philibert, Philippe Halfon, Gisele Philip, Veronique Lambry, Patricia Jolly, Marie Emmanuelle Mars-Kallee
Triple drug therapy containing either a PI or 3 NRTIs is recognized as the standard of care for HIV-1 infection. Although similar rates of undetectable viremia are obtained with these 2 regimens in naïve patients, it is not well known what are the differences in potency in terms of residual HIV-1 replication when plasma viral load is controlled.
Enfuvirtide (ENF, T-20), a HIV-1 fusion inhibitor, added to optimized background (OB) regimen provides additional viral suppression compared to OB alone in highly antiretroviral-experienced patients.1 A Markov model was developed to predict the relative clinical prognoses of patients receiving ENF + OB or OB alone from changes in virological and immunological response found in a Phase III trial (TORO 1; T-20 vs. Optimized Regimen Only).
Giuseppina Liuzzi, Mauro Zaccarelli, Simone Topino, Alessandra Amendola, Daniela Zinzi, Mariarosaria Capobianchi, Pasquale Narciso, Carlo Federico Perno, Andrea Antinori1
The efficacy of sexual transmission of HIV primarily depends by the concentration of infectious virus in semen. In order to evaluate the effectiveness of a widely used antiretroviral regimen in reducing HIV viral load in male seminal fluid, we quantified HIV-RNA in semen of HIV patients in treatment with a combination regimen including two nucleoside reverse transcriptase inhibitors and efavirenz (EFV).
C Sabin, C J Smith, M Youle, F Lampe, M A Johnson, A N Phillips
Although albumin is a strong predictor of mortality over both the short and long-term [1,2], little is known about the factors associated with albumin levels or how levels change in those on HAART. The aim of this study was to describe albumin levels in 101 patients who started HAART (n=23) or switched a PI or NNRTI (n=78) between October 2000 and June 2001.
George Perez, Rodger Macarthur, John Baxter, Chris Mullin, Barry Schmetter, James Neaton, Sharon Walmsley
This study was designed to compare the long-term clinical efficacy and toxicity of nelfinavir (NFV) or ritonavir (RTV) in patients with CD4+ cells below 200/mm.
To describe the survival of patients with HIV in Edinburgh following the introduction of highly active antiretroviral therapy (HAART). Method Analysis of prospectively collected data from an ongoing observational cohort.
Rosario Palacios, Josefa Ruiz, Mercedes González, Manuel Márquez
To analyse the evolutive features of a cohort of patients with a late stage of HIV infection diagnosed in the HAART era and to study the efficacy of HAART, associated complications and healthcare resource utilization.
Shlomo Maayan, Tania Goslitzer, Ran Nirpaz, Michelle Haouzi1, Klaris Riesenberg, Michael Alkan, Fransic Schlaeffer2, Hewott Nagusa3
To compare the response to HAART in 2 groups of Ethiopian immigrant patients infected by HIV-C and followed at two clinics in Israel, and in one group of non-Ethiopian, non-immigrant patients, infected by HIV non-C. To assess lipid derangements in the study groups.
This study was conducted to assess the experience of twice daily injections of enfuvirtide in patients in two ongoing multinational Phase III trials (TORO 1 and TORO 2) at 24 weeks.
Nuria Camino, Rosa De Julián, Pablo Barreiro, Vicente Soriano, Juan González-Lahoz1
The potency, good tolerance and simple administration of NNRTIs makes them suitable for second-line drugs after PI therapy. The NNRTIs have been proved to add efficacy to rescue interventions, and to sustain treatment success in simplification strategies. In this context, little is known on the comparative performance of the two available NNRTIs (NVP and EFV).
Brian Conway, Salima Jutha, Michelle Jones, Jennie Prasad, Amanda Roze Des Ordons, Robert Reynolds, John Farley1, Nadine Smith, Annabel Mead, Stanely De Vlaming2
DLV is a non-nucleoside reverse transcriptase inhibitor (NNRTI) whose specific role in therapy remains undefined. The fact that it is an inhibitor of CYP3A4 and CYP2D6 may make it useful to increase the concentration of protease inhibitors (PIs) in combinations to be prescribed to previously treated patients and to avoid the need to increase methadone (MET) doses in IVDUs receiving HAART.
There is concern that long-term benefits of HAART can be threatened by incomplete control of HIV viraemia caused by drug resistance of HIV, adverse effects and poor adherence. Our aim was to find out how plasma viral loads evolved over time among our patients on HAART.
S Das1, A Joseph2, V Harindra, M Browning3, K Yoganathan, J Tobin4, A Wade, P S Allan5
Nevirapine, a non-nucleoside analogue, has demonstrated suppression of Human immunodeficiency virus (HIV) replication alone and in combination therapy. However, the durable suppression of HIV with nevirapine when used along with other nucleosides in HIV-infected patients needs further evaluation.
Highly active antiretroviral therapy with a protease inhibitor (PI) is widely used. Due to metabolic side effects and impaired adherence caused by high pill burden, there is a desire to switch to a PI-free regimen. The aim of the study was to assess the virological and immunological status of HIV-1 infected adult out-patients during one year of HAART including nevirapine (NVP).
Giorgio Gatti, Cleta Raffaella De Pascalis, Andrea De Luca, Antonio Di Biagio, Patrizia Zucchi, Renato Maserati, Laura Trentini, Stefano Bonora, Paola Meraviglia, Dante Bassetti1
The study objectives were to evaluate (a) possible predictors of virologic and immunologic outcome and (b) the relationship between virologic and immunologic outcome in deep-salvage HIV-positive patients receiving an amprenavir (APV)-containing regimen.
R Bucciardi, V Fragola1, R L Goodall2, B Conway, D Churchill, A Mijch, A Orani, M Schechter, J Weber, on behalf of the INITIO Co-ordinating Committee3
INITIO is a large randomised trial in progress, designed to evaluate three different therapeutic strategies using combinations of the three classes of anti-retroviral drugs. 913 antiretroviral therapy (ART) naïve individuals from 17 countries have been enrolled, of whom 148 individuals from 5 countries (Australia, Brazil, Canada, Italy, UK) are participating in a Quality of Life (QoL) substudy.
Jean-Michel Livrozet1, Nora Berra, Jean-Louis Touraine2, Isabelle Ravaux3, Lise Cuzin4, Elisabeth Bouvet5, Jean-Pierre Stahl6, David Rey7, Bruno Hoen8, Renato Fiore9, Elisabeth Rouveix10 Jean-Pierre Bru11 Pascal Chavanet12
Post Exposure Prophylaxis (PEP), using two nucleoside reverse transcriptase inhibitors (NRTIs) and one protease inhibitor (PI), is recommended in France since 1998, but side effects adversely affect adherence.
Jean-Marie Ragnaud1, Benedicte Delmas2, Herve Gallais3, Dominique Peyramond4, Henri Laurichesse5, Pierre Dellamonica6, Jean-Luc Pellegrin7, Thierry Allegre8, Nathalie Audebert9, Jacques Reynes10 on behalf of InfectioSud group
To evaluate efficacy and safety of switch to Trizivir (TZV) at week 24 in HIV-1 infected patients (pts) initially treated with a quadruple therapy.
Louis Lupo, Jen-Fue Maa, Christopher Dezii, Deena Said, Laura Bessen, Sally Hodder1
Racial differences in the efficacy of drug therapy have recently been described. This post-hoc subgroup analysis investigates time to virologic and treatment failure among various racial groups in a multinational clinical trial.
To evaluate the efficacy, immunological outcome and safety of an amprenavir/ritonavir containing regimen in PI-pre-treated patients in routine clinical practise.
Pompeyo Viciana1, Rogelio Perez2, José Hernández Quero3, Jose Juan Hernández Burruezo4, Pablo Labarga5, Antonio Vergara6. and the NNIP Study Group
NNRTI therapy is currently used very frequently, however there is no information from clinical trials that describe how these treatments can be salvaged. The objective of this study was to obtain information about the NNRTI salvage with PI’s (nelfinavir 1.250 mg bid in PI naïve patients failing NNRTI and saquinavir/ritonavir 1.000/100 bid in PI experienced patients failing NNRTI).
Andrew Owen, Patrick Hoggard, Saye Khoo, Anthony Hart, David Back1, Patrick Bray, Stephen Ward2
The need for low cost alternatives in HIV therapy has led us to examine the antiviral potential of a range of antimalarial agents. Chloroquine (CO) has recently been shown to have in-vitro activity against HIV at clinically achievable concentrations, possibly by a post-integrational mechanism.
Juultje van den Berg1, E Hak2, I M Hoepelman, C A Boucher, M M E Schneider3
It has been suggested that HIV-infected patients from resource-poor (non-European) countries have a higher risk of treatment failure than their European counterparts. We compared early and late phase failure to highly active antiretroviral therapy (HAART) in both groups.
Roberto Manfredi, Leonardo Calza, Francesco Chiodo1
The immigration towards Italy is a recent phenomenon, but it brought to our attention patients (p) coming from areas which are highly endemic for HIV infection, or were exposed to HIV after their arrival in our country, due to the poor economic, social, and healthcare conditions of novel immigrants.
Roberto Manfredi, Leonardo Calza, Francesco Chiodo1
Saquinavir hard-gel was never assessed as a part of a de-intensification therapy in patients who had a prolonged favourable response to protease inhibitor-containing potent HAART. We present a prospective survey of saquinavir hard gel-naïve patients who resorted to saquinavir hard-gel plus two nucleoside analogues after interrupting indinavir-, ritonavir-, or nelfinavir-based HAART which achieved a viremia below 50 copies/mL since 3-6 months, and refused other HAART regimens.
Roberto Manfredi, Antonio Gramegna, Ginevra Marinacci, Leonardo Calza, Lorenza Fortunato, Marina Tadolini, Gabriela Salvucci, Simona Varani, Francesco Chiodo, Franco Bocchi1
In order to analyze the features of patient population referring to the day hospital service of our infectious diseases division, all hospitalizations carried out from the year 2000 to the first six months of the year 2002 have been assessed according to discharge diagnosis, days of hospitalization, diagnosis-related group (DRG) score, and mean number of admissions per patient.
Roberto Manfredi, Leonardo Calza, Francesco Chiodo1
The emergence of resistance, problems related to patients’ adherence, and short- and long-term toxicity, represent the most relevant causes of antiretroviral therapy failure. In patients who received a long-term prior anti-HIV treatment, a combination between multiple genotypic resistances and severe drug intolerance may make extremely difficult the selection of a combination antiretroviral regimen which is expected to be concurrently effective and safe.
Roberto Manfredi, Leonardo Calza, Francesco Chiodo
Aim of our survey is to compare the healthcare resource consumption (including the progressively increasing administration of HAART, and the use of other prescription drugs and therapies for HIV disease management), with the trend of the major end-points of HIV disease progression (AIDS notification and mortality index), in a nine-year-long monitoring of our cohort of around 1000 patients, in order to give an estimate of the balance between economic features and evolution of clinical care of HIV disease.
Y R Sitdykova, A V Kravchenko, V V Beliaeva, V V Serebrovskaya, A G Gurgenov, A Y Pronin, V V Pokrovsky1
To evaluate safety and efficacy of regimen with saquinavir SGC (FTV, Fortovase), ritonavir (RTV, Norvir), didanosine (ddI, Videx) and phosphazid (Nicavir, monophosphanat of AZT) in HIV-infected treatment naïve patients.
Robert Jablonka, Stefan Esser, Maija Koppermann, Johanna Huczalla, Manfred Goos1
To evaluate the efficacy and tolerability of RTV-boosted APV-based salvage regimens in heavily pretreated patients after virological, immunological or clinical failure of previous antiretroviral therapy (pART).
Sorin Petrea, George Jugulete, Mariana Mardarescu, Monica Luminos1
There are over 4,000 children living with HIV/AIDS according to the Romanian Public Health Ministry. In our clinic we have registered over 900 HIVinfected children, 90 % are treated with antiretroviral therapy (ARV). Approximate 80% of HIV-infected children have HAART.
To assess the effectiveness of palliative paediatric care and counselling using a holistic approach to improve the quality of life of HIV-infected and affected children.
G Jugulete, M Dragan, M Mardarescu, M Luminos, S Petrea1
There are over 10,000 HIV-infected children registered on Romanian Public Health Ministery. In our clinic we have registred over 950 HIV-infected children, 90% are treated with antiretroviral therapy (ARV). Approximate 80% from HIV-infected children have HAART.
Hermione Lyall, Stephen Head1, Sarah Gibbons, Saye Khoo2
There were 11(21%) low KAL levels, including 4 undetectable, median - 431 ng/ml (172-1,382). 28(53%) levels were in the acceptable range, median – 8,168 ng/ml (1,762-12,991). There were 14 (26%) high levels median – 16,765 ng/ml (pre dose 12,427 - 42,255). Non-adherence was contributory in 7/8 children who ever had low/undetectable levels, the eighth child was a three month old infant commenced on an initial low dose of KAL. At last visit 4/8 of this group of children had VL < 50, and 7/8 had subsequent acceptable KAL levels. Five children always had levels within the acceptable range, at last visit 2 had VL <50, 2 had VL still declining (60 & 212 copies / ml) and one had virological failure. Seven children had at least one high KAL level, at last visit 6/7 had VL <50, and one had virological failure. A possible relationship between high KAL levels and maximal lipid levels is under further study. In this small cohort, measurement of KAL levels
identified non-adherence early enough for intervention, however there were a worrying number of high levels.
Hermione Lyall1, Stephen Head, Sarah Gibbons, Saye Khoo2
Measurement of EFV levels in this small cohort of children has been helpful in assessment of adherence and drug metabolism. Larger studies are required to determine the additional effect of therapeutic drug monitoring in children.
Although median changes over time were relatively small in this cohort of children on KAL, a worrying number of elevated levels occurred. This is of concern for the longterm cardiovascular health of these children. Median change in Cholesterol (mmols), Triglyceride (mmols) and Chol/HDL ratios from baseline.
Pieter Fraaij1, Alina Bergshoeff2, Jennifer Ndagijimana3, Annemarie Van Rossum1, Nico Hartwig1, David Burger2, Ronald De Groot1, Horst Schroten3, Tim Niehues3
1) Dual therapy with EFV and LPV/r results in optimal viral suppression in children who were pretreated with NRTIs. 2) CD4+ T-cell counts show a tendency to increase after previous suboptimal suppression of the virus. 3) Side effects included a rash and elevated serum cholesterol levels.
HAART was introduced in Poland in 1997. Since then the following drugs are available: NRTI - ZDV, 3TC, ddI, d4T, tenofovir (since 2002), PI - NFV, RTV, IDV, LPV/RTV, NNRTI – NVP, EFV. Since 2001 the recommendations for HIV-infected children include 2 NRTIs and 1 protease inhibitor or 1 non-NRTIs.
The purpose of the study was the assessment of clinical, immune, virological status of children with AIDS who were treated using therapy Highly Active Antiretroviral Therapy (HAART). Twenty-five patients were studied with AIDS (C1-C3 category), who had been treated before with antiretroviral agents.
Dominik Dunsch, Richard Linde, Ziju Elanjikal, Wolfhart Kreuz, Thomas Klingebiel1, Caroline Faul-Burbes2, Anette Haberl3,
Our results show, that in all cases of premature craniosynostosis COV during pregnancy was given and therafter newborns were treated with AZT according to ACTG076. We suspect that the incidence of premature craniosynostosis in HIV-exposed children might be higher than in normal population. In order to prove this hypothesis further investigations on premature craniosynostosis and HIV-exposition are neccessary.
Roberto Manfredi, Leonardo Calza, Francesco Chiodo1
The emerging of extensive multi-drug antiretroviral resistance represents a growing phenomenon also among children with vertical HIV disease, especially when HIV infection has been treated since birth, and suboptimal regimens have been administered for a long time, waiting for the availability and/or the registration of potent HAART regimens.
Adriana Ammassari, Alessandro Cozzi-Lepri, Maria Paola Trotta, Anna Cappelletti, Sara Melzi, Patrizio De Longis, Mauro Zaccarelli, Vincenzo Vullo, Rita Murri, Paola Piano, Sergio Lo Caputo, Salvatore Nappa, Francesco Baldelli, Antonella D’Arminio Monforte, Andrea Antinori, Massimo Galli
Better HAART adherence is associated with a higher risk of faster subsequent development of ATA. Patient-perceived fat accumulation but not prior clinical diagnosis of ATA seems to negatively affect medication intake.
CT patients have a greater understanding of HIV infection and ART compared to NCT. Virological outcome one year post commencement of antiretroviral therapy was significantly better in those in CT, however there was no significant difference in CD4 counts at one year. Further sub-analysis to elucidate reasons for failure in each group need to be performed.
Aisling O’Hagan, C Bergin, F Mulcahy, C Merry, L McCullagh1
Prescription charts for all outpatient, in patient and day-ward HIV patients are reviewed daily by specialist pharmacists, to help ensure safe, cost effective and appropriate prescribing. The aim of this prospective study was to record all pharmacy interventions made in a two-week period in July 2002 and to obtain qualitative data for teaching, peer review and audit purposes.
Maria Paola Trotta, Pasquale Noto, Andrea Antinori1, Adriana Ammassari, Rita Murri2, Alessandro Cozzi-Lepri3, Cristina Minardi4, Giancarlo Orofino5, Luigina Tacconi6, Francesco Alberici7, Guglielmo Nasti8, Maria Ciardi9, Antonella D’Arminio Monforte10
To assess the relationship between: 1) different indirect measures of HAART adherence (patient-report, physician-estimate) and plasma drug levels; 2) these adherence measures and HIV RNA.
To analyse the attitude and knowledge of German physicians involved in HIIV treatment on the role of adherence in ARV treatment, their assessment of their patients' degree of adherence, the factors influencing adherence and their intervention strategies they use to support and increase adherence to HAART.
Interruption of treatment and non-adherence are fairly common in management of HIV/AIDS patients especially in developing and resource limited settings. In this study, reasons for drug interruptions and non-adherence as well as the prevalence in the various drug classes were studied in five HIV/AIDS clinical centers in Nigeria.
Rita Murri, Adriana Ammassari, Andrea De Luca, Patrizia Marconi, Cecilia M J Drapeau, Rosaria Politi, Roberto Cauda, Antonella Cingolani1
Adherence (Adh) to drugs is crucial for treatment efficacy. Objective of the study was to evaluate predictors of virological failure (VF) in HIV positive pts taking HAART.
The aim of this study was to examine the role of objective and subjective barriers to optimal adherence to HAART. In a cross-sectional study in 9 UK centres, patients completed questionnaire measures of subjective barriers to adherence including concerns, perceived necessity and perceptions of the intrusiveness of HAART.
Brian Conway, Salima Jutha, Michelle Jones, Jennie Prasad, Amanda Roze des Ordons, Robert Reynolds, John Farley1, Annabel Mead, Stanely DeVlaming, Nadine Smith2
The treatment of HIV-infected IDUs presents unique challenges, including the need for high levels of adherence. The availability of directly observed therapy (DOT) allows us to address this issue in a meaningful way, but many of the patients may already have received treatment and experienced a virologic breakthrough, potentially compromising the success of any future interventions.
P95: Drug-specific measures of adherence to PI therapy most predictive of short and long-term clinical outcome
C A Donnelly, R M Anderson, N M Ferguson, A C Ghani1, J Hooper2, S Mayer3, D Lapins4, J Stansell5
Anna Gatti, Fabio Arpinelli, Giovanni Visonà, Ruggero Panebianco1, Giuliano Rizzardini2 on behalf of ADEQUA Study Team
Adherence to HIV therapy and QoL are becoming the most important factors in conditioning long term treatment outcome. ADEQUA is a perspective, multicentre observational survey aiming to measure adherence to anti-HIV treatment and quality of life (QoL) of Italian patients (pts).
James Jordan, Jerry Tolson1, Tom Delea, Miwako Hagiwara, Gerry Oster2, Anke Richter, Beth Sherrill3
This study was conducted to assess whether fixeddose combinations (FDC) improve HIV-1-infected patients' adherence to antiretroviral therapy (ART) in community practice.
James Jordan1, Pedro Cahn2, Frank Goebel3, Sophie Matheron4, Clare Bradley5, Alison Woodcock5
In all three studies, therapy with ABC containing regimens resulted in significantly greater patient satisfaction with treatment than single PI containing regimens.
Although few patients are currently receiving once-daily therapy there is clear patient demand. Patients anticipate that reducing the number of pills taken by even 2 pills per day would have a positive effect on adherence and that reducing the number of intakes would reduce the likelihood of forgetting to take medication.
Giustino Parruti, Giuseppina Placido, Luciana Alterio, Augusta Consorte, Patrizia Marani Toro, Vittoria Graziani, Adriana Agostinone, Alessandro Pieri, Giuseppe D’Amico, Rocco Vittorio Graziani, Giuseppe Marani Toro
Our results add further evidence to the knowledge that longterm adherence to HAART is a major determinant of persistent suppression of HIV1 replication once undetectable viremia has been reached with any association of drugs. Furthermore, our data provide clear evidence that favourable socio-economical conditions may be predictive of good adherence to therapy, at least during the first 18 to 24 months of HAART treatment.
D Sedlacek, R Sedlackova1, I Subrt2, I Vobrubova2, M Stankova3, S Snopkova4, J Kolcakova5, V Chmelik6
Relatively high number of heterozygous 32-bp deletions among studied patients was found. The development of new medications and treatment approaches (STI, simplifications etc.) can be expected in the future. Therefore, we suggest that patients are tested for the presence of deletion of 32-bp for CCR5 gene before the start of the treatment with HAART therapy. The influence of further chemokine receptors statuses on the treatment with HAART therapy should be subject to further research.
Delay in the diagnosis of advanced HIV infection may lead to avoidable morbidity and mortality, particularly in the modern era of highly effective anti-retroviral drug therapy. Clinicians need to consider HIV infection in the differential diagnosis of a variety of common presenting symptoms to ensure timely diagnosis and therapeutic intervention.
Margit Halvarsson1 ,Björn Södergård2, Pehrolov Pehrson3
The decreasing amount of reported side effects might be explained with better drugs. Adherence has increased during all three measuring-periods and one possible explanation might be our increased attention on adherence at the clinic but the number of pills has also decreased and the dosing schedule is becoming easier. The level of social support seems on the other hand to decrease possibly effecting adherence negatively. Even if the median treatment time in total is as long as 66 months, 50 % of the patients still report that they never miss a dose.
B Clotet1, F Pulido2, J Carmena3, I Luque4 on behalf of Trizivir 1000 Study Group
Subjects who switched from current treatment to TZV demonstrated an improved lipid profile and reported high levels of adherence and increased general satisfaction.
The results from this study indicate that simpler medication regimens containing fewer tablets, and the use of reminder devices may help to improve adherence. Adherence levels varied between different patient groups in our study population indicating the need for adherence enhancing strategies and support targeted for certain groups, such as IVDUs and non-Norwegians.
Annabel Mead, Stanley de Vlaming, Nadine Smith1, Amanda Roze des Ordons, Brian Conway2
We have evaluated 10 patients, 4 of whom were treatment naïve. Concomitant medication included 2 NRTIs for all patients, with one patient also receiving an NNRTI. Median baseline CD4 counts and plasma viral load measures were 140 cells/mm3 and 92,000 copies/mL respectively. After a median follow-up period of 6 months, these values were 250 cells/ mm3 and 120 copies/mL, with 8/10 individuals showing virological suppression of <400 copies/mL. There was ongoing cocaine use in 8/10 patients (> 80% of drug urine screens positive in half of the patients). The two patients who did not experience good virological suppression were heavy cocaine users with poor adherence. The mean methadone dose prior to the initiation of HAART was 88 mg/day, and stabilized at a similar level (92 mg/day) on therapy. Similarly, there was no significant change in ALT (55 IU/L vs. 42 IU/L).
The above study shows that the effectiveness and success of TB prophylaxis in HIV-positive patients does not depend on strict adherence to antiretroviral treatment, there are other factors like resistance to drugs and poor nutrition which should be considered as well.
M Hooker, R L Goodall1, B Conway, D Churchill, P-M Girard, A Mijch, F Mulcahy, B Salzberger, S De Wit2 for the INITIO Co-ordinating Committee
Rates of LAS/SHL were observed to be significantly increased in people with high BMI, and higher in women, although the differences between the sexes was not significant.
Francisco Blanco, Teresa García-Benayas, Vincent Soriano, Juan González-Lahoz1, Juan José De La Cruz2
In naïve HIV-positive pts who start HAART, ddI-d4T regimens induce a higher increase in lactate levels as compared with AZT-3TC combinations, even within the first months of therapy. This fact should be considered when deciding the first-line antiretroviral regimen, in order to prevent future clinical toxicity such as lactic acidosis. An increase in LDH and amilase levels could alert on the possibility of hyperlactatemia, and lactate levels monitoring could be advisable in such cases.
Helena Brett-Smith, Victoria Rutkiewicz, Anne Cross
Stavudine XR/PRC is well tolerated in combination with 3TC and EFV and shows comparable overall safety to the matching IR regimen. The data suggest a trend towards lower rates of medically important PNS events with the XR/PRC formulation.
Teresa García-Benayas, Francisco Blanco, Vicente Soriano, Juan González-Lahoz
Replacement of d4T by ABC is safe and provides early and sustained metabolic benefit achieving significant and progressive reductions in lactate levels at 6 and 12 mo. This strategy confirms in vitro data regarding different degree of d4T and ABC induced mitochondrial damage and might be useful to lower potential toxicity, as long as NA remain an essential part of HAART.
K Prime, S G Edwards, M R Pakianathan1, F Scaravilli2, R Miller3
Since the introduction of HAART, the spectrum of problems encountered by HIV physicians has widened to include pathology related to antiretroviral (ARV) therapy. Furthermore as patients survive longer, an ageing cohort of HIV positive patients is being encountered who may develop other chronic medical conditions.
Patients treated with antiretroviral therapy must be promptly stopped to take some specific NA in case of symptoms correlated to lactic acidosis. This study shows, like many others, that in patients treated with NA the most frequent correlation with HL is linked to some specific drugs. In our opinion the routine measurements of lactate level is not necessary because of low incidence of symptomatic patients despite the moderate rate of asymptomatic HL.
M Harris, HCF Cote, JW Chan, J Asselin, M Valyi, PR Harrigan, MV O’Shaughnessy, JSG Montaner
No significant change in lactate level was observed in 8 patients who had normal baseline lactate and were switched to TDF for other reasons (p=0.95). The switch from d4T to TDF maintained antiviral effect and resulted in decreased MCV, increased mtDNA/nDNA, and decreased lactate in patients with hyperlactatemia at baseline.
S López1, A Beato, J Casademont, F Cardellach, Ò Miró2, M García, E Martínez, A Milinkovic, J L Blanco3, B Rodríguez4,
Depletion in MtDNA occurs during HAART leading to a primary general MRC dysfunction and, consequently to hyperlactatemia as a final phenotypic expression. Our data seems to confirm that mitochondrial dysfunction relies at the basis of developed hyperlactatemia during HAART.
Discontinuation of NRTIs, as well as a supportive treatment with physiotherapy, analgesics and vitamin B lead to a quick clinical improvement. After approximately one month all biochemical parameters had returned to normal, although, three months were needed for the patient to recover completely, motor weakness being the most persistent symptom.
A Arenas-Pinto, I V D Weller1, A D Grant2, S Edwards3
NRTIs use and female gender appear to be risk factors for the development of LA. What other factors are involved is still not clear but might include; duration of NRTI therapy, specific drug use and genetic predisposition. A case-control study would provide more robust information on the important pre-disposing factors associated with the development of severe LA.
Daniela Gey, R. Boit, T. Lorenz, M. Hartmann1, F. Mosthaf2, P. Langmann, H. Klinker3
Evidence of mitochondrial toxicity, such as high lactate levels and polyneuropathy and lipoatrophy from NRTIs are common problems and often necessitate a change of the current regimen of antiretroviral therapy (ART). So far, only few studies investigated NRTI-free regimens.
Alteration of serum lactic acid levels, although asymptomatic in the majority of cases, is a novel and emerging complication of HIV disease and its treatment, interesting over one third of HIV-infected patients in our experience. Although most of literature data are anecdotal, and we lack of controlled, prospective studies dealing with frequency, risk factors, and out- come of this phenomenon, mythocondrial damage possibly caused by antiretroviral drugs is the first possible origin, from a pathogenetic point of view, although our series failed in demonstrating a correlation with each single nucleoside analogue. A relationship with the overall duration of anti-HIV therapy (including HAART, and always based on nucleoside analogues), and other emerging toxicity with common or related pathogenetic pathways (i.e. dyslipidaemia, skeletal muscle damage), is highly suspected.
Pharmacokinetic data released by the manufacturers of TDF have confirmed that simultaneous administration of TDF and ddI increases ddI AUC and Cmax by 60% and 64% respectively (1). Pancreatitis is a wellrecognised complication of ddI and since TDF increases systemic exposure to ddI it is reasonable to assume that co-administration of ddI and TDF will increase the incidence of ddI-related toxicities – as was the case with our patient. We therefore advise extreme caution in the combination of ddI and TDF in any regime, but if unavoidable dose reduction of ddI should be considered and should be closely monitored for ddI-associated adverse events.
M Ribell Bachs, A Soler, M Perez, G Casas, E Pedrol1, C Villa2
NRTIs have been associated with mitochondrial toxicity. Mitochondrial dysfunction leads to different clinical features, being lactic acidosis (LA) one of the most threatening events. Suppletion of essential co-factors such as thiamine, L-carnitine, piridoxine; artificial electron acceptors and antioxidants such as vitamin C, have been tried out on mitochondrial diseases with varying success.
Mitochondrial toxicity causing hyperlactataemia, lactic acidosis and hepatic steatosis are well-recognised adverse effects of Nucleoside Reverse Transcriptase Inhibitors (NRTI). We report four HIV-positive patients who were on stavudine (d4T) and didanosine (ddI) as part of anti-retroviral therapy (ART).
Stephanie Badiou, Corinne Merle de Boever, Anne Marie Dupuy, Vincent Baillat, Jacques Reynes, Jean Paul Cristol
Advanced stage of HIV infection is associated with an atherogenic lipid profile including a high prevalence of small dense LDL. Lopinavir/ ritonavir-containing regimen accentuate the reduction of LDL size. Since fibrates decrease APOCIII expression and increase LDL size, they appear as a logical strategy to manage HAART-induced HTG [4,5].
Leonardo Calza, Roberto Manfredi, Francesco Chiodo
All used statins and fibrates revealed a similar, significant efficacy in the treatment of diet-resistant hyperlipidaemia, but further studies seem necessary in order to establish the most appropriate guidelines for the management of dyslipidaemia associated with highly active antiretroviral therapy.
RTV in a dose of only 100 mg bid exerts adverse effects on SLPs by increasing total cholesterol, LDL cholesterol and triglycerides and decreasing HDL cholesterol. The addition of LPV 400 mg bid to RTV 100 mg bid partially abrogates this effect by increasing the HDL cholesterol without affecting LDL cholesterol or triglycerides.
Massimo Galli1, Anna Lisa Ridolfo, Alessandro Cozzi-Lepri, Antonella d’Arminio Monforte, Cristina Gervasoni, Mauro Vaccarezza, Anna Cappelletti, Antonio Chirianni, Francesco Mazzotta, Umberto Tirelli, Alfredo Scalzini, Paola Morelli, Erika Gianelli, Manuela Piazza, Mauro Moroni2
In this longitudinal study MA are confirmed to be frequent finding in patients on ART. HT appears earlier and is the only alteration clearly influenced by both individual and specific drug esposure.
Antonio Rivero1, Jean-Francois Delfraissy2, Alexey Yakovlev3, Alexandra Thiry, Michael Giordano4, Shannon Schrader5
ATV once daily as part of a HAART regimen, like EFV, is not associated with the development of insulin resistance as assessed by fasting insulin, C-peptide, and glucose concentrations. This is unique among PIs and consistent with ATV’s effect on GLUT-4 in-vitro. In addition, ATV is associated with reduction or minimal increases in lipid concentrations through 24 weeks. Most patients on either regimen had favorable TC/HDL-C ratios.
Treatment for HIV disease with HAART is associated with elevation of serum cholesterol. We report on the use of atorvastatin and pravastatin to reduce serum cholesterol in HIV-positive patients receiving HAART.
S Das, G Gilleran, R Cramb, M Shahmanesh1, M Stolinski, W Jefferson, N Jackson, M Umpleby2
This study suggests that protease inhibitors increase hepatic VLDL secretion. This provides a mechanism for the increase in plasma triglyceride levels found in patients on PI.
J Garcia, FJ Rodríguez, JM Lomas, I Chaparro, D Merino, E Pujol
An increase in glucose, cholesterol and triglyceride levels can be seen after two years of HAART, though glucose increase does not reach significance. HAART produces a significant metabolic profile change, though it is frequently left untreated.
Henna Jalee, Ade Apoola, Mohsen Shahmanesh1, Rob Cramb2
In a cohort where 90% of were also on AZT/3TC no differences in the rise in serum lipids between PI, NVP and EFV were seen. Rising levels of Lp-a was seen only with EFV. Results should be interpreted with caution because of the small numbers.
Omar Janneh, Patrick G Hoggard, Sean D Sales, Simon P Jones, John F Tjia, Saye H Khoo, Bridget Maher, David J Back, Munir Pirmohamed
We conclude that PIs decrease the adipocyte triglyceride accumulation, promote lipolysis, affect adipocyte viability and increase the secretion of TNF-α from fat cells, indicating that they play a central role in the dysregulated fat metabolism observed in lipodystrophy. These data are in agreement with published reports that PIs suppress the differentiation of preadipocytes and promote adipocyte death [3].
M L Montes, JR Arribas, C Barros, F Pulido, F Dronda, J Berenguer
In real life the early increase in cholesterol after lopinavir/ritonavir-based HAART is similar to the increase described in clinical trials. Increases in triglycerides are considerably less pronounced than in clinical trials probably due to fasting. Patients with high baseline cholesterol have a higher risk of developing hypercholesterolemia after 8 weeks.
C Vernochet, G Ailhaud, C Dani1, S Azoulay, D Duval, R Guedj2
Thus i) chosing the cell model is important to study the effect of a given PI on adipocyte proliferation and differentiation and ii) ritonavir is postulated to have intracellular targets.
All but one patient experienced a persistent increase of at least 18% in CD4 counts (range -2% - 1095% with paired t-test p value <0.5. Viral load levels were decreased in parallel at a statistically significant level in all patients.
ABT-378/r plus amprenavir along with at least two other antiretroviral drugs, of which one sensitive according to virtual phenotype, induced a potent decrease in viral load values that persisted 9 months afterwards in 7 MPI patients. CD4 cell increase was also noted in parallel. Therefore, this novel salvage treatment was highly effective in MPI HIV-positive patients. Further monitoring versus treatment time is required in order to confirm sustainment of successful treatment.
Wendy Wobeser, Terri Liu, Peter Ford, Robert Ross, John Fotheringham1, Siamak Tenzif2
Exogenous testosterone is indicated for HIV associated wasting syndrome, however, the effect of exogenous testosterone on body habitus changes in HIV is not known. This was a cross sectional study of males with HIV infection on antiretroviral therapy including those on and not on exogenous anabolic steroids to determine if there was a difference in body habitus (using MRI), metabolic factors and quality of life (MOS-HIV). Multiple variable linear regression was performed to analyze associations with visceral fat (L4/5 on MRI).
U Hengge, K Stocks, S Unger, V Exner, S Esser, M Goos1, S Faulkner, R Dudley2
Oxymetholone was found to have true anabolic effects in a double-blind, placebo-controlled phase III trial. The BID (100 mg/d) regimen appeared equally effective to TID (150 mg/d) dosing while displaying reduced liver toxicity. Due to its favourable protein anabolism, it may be recommended for therapy of wasting and lipodystrophy in HIV-infected subjects.
E Martínez, J M Gatell, A Milinkovic, J L Blanco, M Laguno, A Leon, J Mallolas1, L Paddam, A N Phillips2
Although relatively few cases of lipodystrophy have occurred in this cohort to date, the identification of baseline fasting triglycerides as a risk factor for lipodystrophy in these patients may be an important finding. Further analyses are warranted to clarify the possible role of particular drug regimens in the progression to lipodystrophy.
V Paparizos, K P Kyriakis, C Botsi, S Kourkoundi, E Siakavellas, I Zagoraios, N G Stavrianeas
Our study reinforces previous observations regarding the relatively increased toxicity of d4T compared to AZT without any confounding effects from a protease inhibitor administration or previous treatment failures.
The increase in glucose and cholesterol in group 2, although statistically significant, was small and is unlikely to be clinically important. The switch group did not show any improvement. Changes in anthropometrical measurements tended towards the phenotype of lipodystrophy but there was no clear difference noted between groups. Of particular note the treatment naïve group showed body changes suggestive of lipodystrophy, indicatative of a multifactorial aetiology and not solely due to therapy.
Roberto Manfredi, Leonardo Calza, Francesco Chiodo
A dimensional increase of the female breast has been reported since early introduction of protease inhibitor-based HAART, and it was considered as an untoward effect possibly part of the fat redistribution syndrome. Less than 10 cases of true gynecomastia have been described by the international literature until now as a possible consequence of antiretroviral therapy (usually containing protease inhibitors), although other concurrent risk factors for gynecomastia were not carefully excluded in all the described reports. Our experience underlines the emerging of true gynecomastia in patients never treated with protease inhibitors, but receiving nucleoside analogues since many years (stavudine in all cases), efavirenz in two cases, and nevirapine in the remaining patient. The long-term persistance of gynecomastia and the frequent association with lipoatrophy syndrome and metabolic disorders, may induce to suspect a possible common pathogenetic
pathway. The possible role of long-term stavudine administration, first suggested by Melbourne KM et al. (Ann Pharmacother 1998; 32:1108), seems to be con- firmed by our report. Also gynecomastia may be included among potential long-term adverse events of antiretroviral therapy even in patients never treated with protease inhibitors. This phenomenon deserves further epidemiological, pathogenetic, and clinical investigation, in order to assess all possible risk factors, and to plan eventual preventive measures.
P Vazquez, A Castro, S Lopez, J D Pedreira1, A Blanco, A Marino2, E Losada, A Prieto3
Mild-to-moderate hepatotoxicity was common in HIV-1-infected patients receiving nevirapine-containing regimens, but was only discontinued in 3.4% of patients. Prior exposure to antiretroviral drugs, hepatitis C virus and abnormal baseline levels of gammaglutamyl transferase were associated with higher risk of hepatotoxicity.
Michael Imperiale, Stephan Lanes, Jerry Stern, Jim Love, Patrick Robinson, Douglas Mayers1
Abnormal liver function tests (LFTs) are common in HIV patients receiving highly active antiretroviral therapy (HAART). However, a perception exists that these events are more frequent with nevirapine (NVP)-based regimens than with other HAART regimens. In order to investigate the role of NVP and other possible risk factors, we have studied a large observational cohort.
Michael Imperiale, Stephan Lanes, Jerry Stern, Jim Love, Patrick Robinson, Douglas Mayers1
A number of cohort studies and prospective analyses have demonstrated that the incidence of asymptomatic elevations of ALT and AST is similar for all antiretrovirals and is associated with viral hepatitis co-infection and elevated baseline values.
Michael Imperiale, Stephen Storfer, Jerry Stern, Douglas Mayers1
Analysis of controlled studies of nevirapine (NVP) have shown that the risk of rash-associated hepatic events is increased in women with CD4+ cell counts >250 cells/mm3 and in men with counts >400 cells/3
G Matthews, G Salamov, S Mandalia, M Nelson, BG Gazzard1
Nevirapine (NVP) is known to cause hepatotoxicity in a proportion of patients who initiate HAART. However, there have been suggestions that the association between abnormal liver function tests (LFTs) and NVP is often overestimated.
Liver dysfunction is common among HIV-infected patients. Drug abuse, hepatitis C virus coinfection, and medications are common causes. Efavirenz-based HAART seems less hepatotoxic than other modalities of HAART. Nevertheless, information about it is limited, and more data are needed.
G Doherty, Y Gourlay1, R Wong, R A Seaton, R Fox, D Kennedy, S Eves2, R Nandwani, A Scoular, AWinter3
The incidence and duration of CNS side effects and rate of discontinuation were all higher than previously reported [1–3]. Patients with a psychiatric history have a higher incidence and duration of CNS side effects. Switching therapy to nevirapine, and or starting an antidepressant or hypnotic may be effective in managing long-term CNS side effects.
Roberto Manfredi, Leonardo Calza, Francesco Chiodo
Alterations of skeletal muscle tissue, although mostly asymptomatic, represent an emerging but still underestimated toxicity occurring in HIV-infected patients. From a pathogenetic point of view, HIV infection itself and especially its treatment are suspected much more than HIV-related disorders. Our preliminary data stimulate further, extensive investigation, including epidemiological, etiopathogenetic, therapeutic, and preventive aspects of this emerging phenomenon.
C Smith, I Levy, CA Sabin, E Kaya, H Gumley, M Johnson, M Lipman1
It has been suggested that HAART may be associated with increased levels of dyslipidaemia. The prolonged survival associated with treated HIV disease makes the reduction of other risk factors for cardiovascular disease important. To describe these risk factors we surveyed 394 HIV-positive patients, investigating their smoking habits, general health and family medical history.
Paolo Maggi, Giuseppe Epifani, Giuseppe Fiorentino, Nicoletta Ladisa, Giuseppe Pastore1, Antonio Lillo, Francesco Perilli, Guido Regina2, Sergio Ferraro3, Miriam Gargiulo, Antonio Chirianni4
In previous studies we observed a higher than expected prevalence of premature carotid lesions in HIV-1-infected patients treated with regimens including PI, compared to naïve patients or patients treated with NNRTI.
Patrick Soentjens1, Bart Ostyn2, Robert Colebunders2,3, Eric Florence3, Steven Van Outryve4, Ann Van De Velde5
A women with HIV infection developed a PVT and secondary splenomegaly, recurrent massive variceal bleeding and thrombocytopenia. The cause of the PVT was probably the acquired PS deficiency with or without PI as a triggering factor.
Marc Hildebrand, Stéphane De Wit, Bénédicte Poll, Elizabeth O’Doherty, Nathan Clumeck
In conclusion, in this small but long term cohort, APV appears safe in terms of lipid profiles and metabolic disorders. The long term safety of the current use of APV/RTV should be further evaluated.
Luciano Nigro, Angela Modica, Francesca Scirè, Anna Onorante, Rosario Russo
In conclusion, although at baseline the two groups, mainly the naïve subjects are not perfectly matched and the observation for the two regimens started in different years, our data in agreement with others, showed that in the short time EFV appears more tolerated than NVP and, in experienced subjects seems to induce better immunoreconstitution and low HIV RNA viral load (<400 copies/ml) for longer period and that in the long term the two drugs present similar profiles.
Torsten Feldt, Klaus Göbels, Mark Oette, Annette Stelzer, Dieter Häussinger
On account of timely coincidence and exclusion of other aetiological causes, we presume primary cardiovascular effects of PEP agents as causative for the incident. An increasing demand for occupational, but also non-occupational PEP after possible HIV exposures is noticed. Apart from frequent mild side effects of antiretroviral therapy, already known severe and life-threatening side effects including nephrolithiasis, acute liver failure, haemolytic anaemia, pancytopenia, lactic acidosis and possible formerly unknown cardiovascular side effects and drug interactions should be considered [2,3,4]. PEP should be restricted to well-documented exposures for which the risk of transmission outweighs the risk of severe side effects.
These data demonstrated a dramatic, significant and increasing cumulative exposure of our patients to both NRTIs and PIs. Metabolic complications secondary to the chronic use of these agents may well become increasingly important and problematic within the context of an aging population with high cigarette use and high prevalence of Hepatitis C infection.
Elevation of CPK did not seem to predict muscle disease and elevation of AM did not seem to predict abdominal symptoms or pancreatitis. If these findings are borne out in larger studies there may be a case for abandoning routine monitoring of these enzymes.
Lisa Almond, David Back, Patrick Hoggard1, Marta Boffito1,2,, Stefano Bonora, Riccardo Raiteri, Alessandro Sinicco, Giovanni Di Perri2
There was considerable variation in both total and unbound NVP plasma concentrations versus a limited variation in NVP unbound % among all subjects studied. In these patients the binding of NVP was not dependent on Ctrough concentration. We are currently comparing ultrafiltration and equilibrium dialysis methodologies for optimising the determination of unbound fraction in clinical pharmacokinetic studies.
Giorgio Gatti, Cleta Raffaella De Pascalis1, Antonio Di Biagio, Dante Bassetti1, Andrea De Luca2, Marco Borderi, Renato Maserati, Stefano Bonora, Leonardo Calza4, Paola Meraviglia6
We found an effect of LPV/RTV and EFV on APV concentrations, which remained significant even when different APV dose strategies were included in the model. In this preliminary analysis, we found a significant and independent effect of gender on APV Cmin. However, the difference in Ctrough concentration between female and male patients was minor and unlikely to be of clinical relevance.
Renato Maserati1, Paola Villani, Maria Cusato, Mario B Regazzi2 Patrizia Zucchi, Laura Sighinolfi, Alberto Catania, Giovanni Guaraldi, Carlo Calzetti, Donatella Giacomazzi, Laura Stoppini, Maria Cristina Rossi, Paula Castelli3
Our results showed that the oral clearance of NFV and the ratio between M8 and NFV was significantly reduced in HIV+/HCV+ pts and it seemed related to the degree of liver function impairment as measured by ALT levels. With a daily dose of 2500 mg, the sum of NFV plus M8 systemic exposure is about 1.25 and 1.5 times higher in HIV/HCV-coinfected patients with ALT values normal to grade 1 and in grade≥ 2 , respectively, than in HIV+ /HCV. individuals.
Stefan Mauss, Florian Berger, Guenther Schmutz1,Stefan Scholten, Juergen Rockstroh2, Eva Wolf, Hans Jaeger3, Michael Kurowski4
Lopinavir levels were reduced about 50% by co-administration with amprenavir in the presence of ritonavir 200 mg bid (AUC12 56,1 µg h/ml vs. 100 µg h/ml) compared to historical study data (Murphy AIDS 2001, 15:F1). Ritonavir 200 mg bid did not lead to higher lopinavir or amprenavir levels compared to ritonavir 100 mg bid (Mauss, et al. AIDS 2002, 16:296). In conclusion an increase in ritonavir to 200 mg did not compensate the reduction of amprenavir AUC by co-administration of lopinavir and vice versa. However it should be noted that therapeutic drug levels can be reached in individual patients with the combination of amprenavir and lopinavir boostered by ritonavir.
Stephen Taylor, D Pillay1, A Veldkamp, B Kappelhoff, A Huitema, J Beijnen2, C Sabin3, S Drake, D White4
In a controlled, prospective study the efficacy of ritonavir 200 mg bid to inhibit the mutual decrease of lopinavir and amprenavir plasma concentration was assessed. 8 HIVpositive patients received amprenavir 600mg bid and ritonavir 200 mg bid for 28 days. At day 14 plasma concentrations of amprenavir and ritonavir were determined over 12 hours.
Diffusion of LPV in semen is low with high inter-individual variability. However, we found HIV-1 RNA to be undetectable in the semen of most patients. Detectable HIV-1 RNA with resistance mutations was observed in semen from 1 patient with detectable viremia and was probably due to an insufficient inhibitory quotient in the genital tract.
M Harris, C Alexander, L Ting, K McNabb, PR Harrigan, MV O'Shaughnessy, JSG Montaner1
Dual boosted protease inhibitors (PIs) are frequently used in rescue therapy. IDV 800 mg twice daily with LPV/RTV was poorly tolerated; therefore, we studied combinations including IDV 600 mg twice daily and LPV/RTV 400mg/100mg twice daily with no NNRTI, or 533/133 with an NNRTI. 12-hr PK measurements were obtained after ≥2 weeks on stable therapy.
Dimitri Schlemmer, François Becher, Alain Pruvost, Christophe Creminon, Jacques Grassi, Henri Benech1, Mickael Levi, Valérie Boutet, Cécile Goujard2
Direct liquid chromatography coupled with tandem mass spectrometry (LC/ MS/MS) assays aimed to quantify intracellular (IC) NRTIs triphosphate (TP) have recently been described [1]. To have a complete view of NRTIs metabolism it is also important to measure plasma or IC NRTIs.
Henri Benech, François Becher, Gaelle Hennere, Dimitri Schlemmer, Alain Pruvost, Jacques Grassi, Frédéric Theodoro1, Cécile Goujard2, Valérie Boutet3
Direct assays aimed to quantify intracellular (IC) nucleoside reverse transcriptase inhibitors (NRTIs) triphosphate (TP) have been recently described [1,2,3]. IC NRTI-TP concentrations and very likely its concentrations ratio versus the endogenous nucleotide-TP competitor are susceptible to describe closely efficacy and/or toxicity of NRTIs.
Sophie Forsyth, Patrick French, Emma Macfarlane1, Sara Gibbons2
In our experience TDM can be used to reduce the risk of HIV treatment intolerance and discontinuation. There is evidence that TDM and dose adjustment reduces IDV nephrotoxicity and that plasma levels of efavirenz and RTV correlate with side effects, however, there are no formal guidelines for the use of TDM in these situations. We recommend that clinicians consider using TDM for identifying possible drug toxicity before switching regimens.
S Gibbons, DJ Back, SH Khoo1, C Taylor2, S Waldron, J Weber3
Although our findings are based on a small number of patients, they suggest that a positive HCV status alone does not predispose to high NNRTI concentrations. However, the presence of altered LFTs may be associated with high plasma concentrations of NNRTIs. TDM may have a role in optimising dosages and reducing drug toxicity.
Sylvie Jorajuria, Dominique Dormont1, Nathalie Dereuddre-Bosquet, Pascal Clayette2, François Becher, Henri Benech, Jacques Grassi3, Alexia Garrigues, Stephane Orlowski4
Altogether, these results showed that 1) pharmacological inhibition of ABC transporters has beneficial effects on the efficacy of anti-HIV drugs, and 2) for AZT, this happens through the inhibition of GAZT efflux.
Christoph Stephan, Manfred Moesch, Amina Carlebach, Schlomo Staszewski1, Nils Von Hentig2, Michael Kurowski3, Stephan Klauke4, Thomas Lutz5
Based on our PK data, the combination of SQV/LPV/RTV is suitable for boosted double PI combination. LPV/RTV co-administration is not less effective to boost SQV compared to RTV. SQV dose adjustment is not necessary. LPV levels either were not affected negatively by SQV.
Andrea Antinori, Alessandro Cozzi-Lepri, Maria Paola Trotta, Giancarlo Fibbia, Pasquale Narciso, Elio Manzillo, Jacopo Vecchiet, Antonella Vincenti, Mauro De Marco, Cristina Mussini, Antonella d’Arminio Monforte, Adriana Ammassari
Self-reported adherent patients were more likely to have adequate plasma drug concentrations than non-adherent patients, and both these measurements were associated with the risk of subsequent viral rebound. A questionnaire on adherence when viral load is suppressed may help to identify patients at higher risk of viral rebound.
R Boit, D Gey, T Lorenz, M Hartmann1, H Klinker, P Langmann2, F Mosthaf3
Antiretroviral therapy in human immunodeficiency virus type 1 (HIV-1)-infected subjects must be frequently changed due to side effects. So far, only few studies investigated nucleoside reverse transcriptase inhibitor (NRTI)-free regimens.
There is no interaction between ddI and TFV in PBMCs as determined by extent of formation of the phosphorylated (active) anabolites of each agent. It is of note that TFV is phosphorylated to a similar degree in Q and S PBMCs while less ddATP is formed in Q versus S cells.
Although nevirapine concentrations greater than 3000 ng/ml are recommended for sustained suppression of viral replication levels greater than 100 ng/ml prevent mother-to-child transmission of HIV-1 and activity is reported against wild-type virus at 10 ng/ml. Despite enzyme induction during therapy nevirapine concentrations with anti-viral activity persist for approximately 7 days after the last dose of nevirapine.
J-C Wasmuth1, C J L la Porte, D M Burger2, K Schneider, E Voigt, J K Rockstroh3
To assess the pharmacokinetics (PK) and tolerability of reduced dosages of BID indinavir (IDV) boosted by low dose ritonavir (RTV) in healthy volunteers.
Marta Boffito1, David Back, Malcolm Rowland2, Terry Blaschke, Veronica Miller3
This report summarises the topics highlighted at the meeting. It will guide the audience through the discussions that allowed the panel to formulate a series of statements regarding the significance of protein binding of ARV drugs both in vitro and in vivo. The discussion also identified some of the research priorities that are important for understanding the sources of inter and intra-individual variability in protein binding in patients. These include obtaining data on unbound concentration as well as total concentration in PK studies; looking at variants of AAG and whether they differ in binding affinity; and emphasizing the importance of developing a standard procedure for phenotypic assays used to determine IC50 values.
Saye Khoo, David J Back1,Marta Boffito 1,2, Stefano Bonora, Anna Lucchini, Agostino Maiello, Ivano Dal Conte, Giovanni Di Perri2
Therapeutic drug monitoring (TDM) may play a role in the individualization and optimisation of existing antiretroviral treatment options. This is particularly true for some specific patient categories, such as those where drug-drug interactions are very likely to occur, in difficult patients affected by comorbidities (i.e. viral hepatitis, cancer), or in patients who harbour viruses with reduced susceptibility to antiretroviral treatment. We here report lopinavir (LPV) plasma concentrations at steady-state (measured by HPLC/MS/ MS) from 5 different HIV+ subjects undergoing treatment with LPV/ ritonavir (r) as part of combination antiretroviral therapy (Table 1. Page 72). Clinical and virological response to protease inhibitors is related to the ratio of drug exposure to viral susceptibility. In all cases shown the information given by TDM improved consistently the management of difficult patients on antiretroviral therapy.
Marta Boffito, Patrick G Hoggard, Helen E Reynolds, David J Back1, Stefano Bonora, Alessandro Sinicco, Giovanni Di Perri2
The intra-individual variability of LPV CCtrough is modest. These data lead support to the applicability of therapeutic drug monitoring of this PI in a clinical setting.
Brian Kearney, Andrew Plummer, John Sayre, Xi Zhang, Andrew Cheng1, Bharat Damle, Kirk Ryan2
Administration of ddI EC 2 hours prior to or simultaneous with TDF and a light meal resulted in elevated ddI exposures relative to ddI EC alone in the fasted state. Further evaluations, including considerations of dosage adjustment for ddI EC, and close monitoring are warranted.
Michael Kurowski, Thomas Sternfeld, Anthony W Sawyer
The mean plasma Ctrough level of APV in patients under routine care corresponds well with data from clinical trials with APV/rtv 600mg/100 mg. Patients with Ctrough levels <700ng/mL belong to a statistically distinct population which may be characterised by non-compliance, pharmacogenetic differences, e.g. concerning the expression of drug transporter genes or other factors, which require further investigations.
Bernd Noack1, Boris Ostapowicz2, Thomas Berg, Stefan Neifer3
In 15% of our patients TDM alone were able to explain the drug failure. This high number demonstrate the significance of TDM in therapy monitoring of HIV-positive patients treated with HAART. Also the genotypic resistance had an higher impact for the explanation of drug failure, TDM gave us further important information. Therefore TDM should be included in an diagnostic algorithm after antiretroviral drug failure.
Mark Oette, Klaus Göbels, Frank Huber, Arne Kroidl, Torsten Feldt, Matthias Wettstein, Dieter Häussinger1, Michael Kurowski2
Co-administration of 4 mg of RG for combined LDS is likely to reduce the bioavailability of EFV. Especially the significant decrease of minimum drug levels is of great clinical relevance. Pooled data show a moderate decrease of 12% in mean levels and 8% in AUC. Thus, routine therapeutic drug monitoring should be performed in all patients treated with EFV and RG to avoid sub-optimal drug levels of ART. RG in a dosage of 4 mg seems to be a safe medication in the treatment of HIV-associated LDS.
David Paar, Dennis Cook, Michael Reardon, Amanda Evans1, Shannon Schrader2
These data indicate that the Ctrough level of NFV may not be associated with virologic success. This also may suggest that TDM, particularly using the Ctrough level for a marker, may not be an appropriate measurement for predicting the success of a NFV containing regimen. These data may suggest that there are other factors that might lead to viral suppression with NFV, such as intracellular drug concentrations, pgp-polymorphisms and concentrations of the active M8 metabolite.
Martin Vogel, Nazifa Qurishi, Matthias Lichterfeld, Carsten Ziske, Thomas Sudhop, Jürgen Kurt Rockstroh, Tilman Sauerbruch1, Hans Christoph Michaelis, Ulrich Spengler2
Concomittant administration of LPV/RTV leads to considerable boostering of CyA-levels. Indeed 1/20 of the usual dosing regime lead to a pharmacokinetic profile desirable for liver-transplanted patients without HAART. These findings underline the need for therapeutic drug monitoring in HIV-infected patients with organ transplantation and HAART.
S Azoulay, F Akeb, R Guedj, D Duval1, M C Nevers, C Creminon, J Grassi2
In conclusion, immunoassays represent a direct, reliable and specific method of quantification of antiretroviral drugs that might be of great interest for individual therapeutic drug monitoring.
Martin Schutten, Ineke Van Der Ende, Ab Osterhaus, Bert Niesters
The CAMv1.5 plasma HIV-1 RNA level assay and the CAMv1.5 HIV-1 proviral DNA assay, which are both based on the same primers and probe set, are used to distinguish HIV-1 from HIV-2 infected individuals for both HIV disease management and epidemiological studies. Our data show that proper distinction between HIV-1 and HIV-2 monoinfection or dual infection in a patient can only be done with additional serological data.
S De Wit, B Poll, N Clumeck1, R Boulmé, J C Schmit2, O Van Der Meeren3
The HIV population starting therapy in Belgium shows a high heterogeneity of HIV sub-types including a significant number of pts infected with mosaics of several sub-types. No difference in VL response at m.12 to a NFVcontaining regimen was found between B and non-B HIV-1 sub-types. A trend to lower CD4 increase at m.12 was observed in non-B patients, particularly when comparing B vs A sub-types. Further analyses are underway to confirm these findings and to establish whether differences in resistance mutations pattern could be involved.
Nicola Mackie1, Simon Dustan, Graham Taylor, Jonathon Weber, John Clarke2
This technique appeared to perform well in a real-life clinic. Drug-resistant mutations were present in patients who were HAARTexperienced with low-level viraemia. Further studies are required to evaluate the optimal clinical approach for the management of such patients.
Ellie Freedman1, Amanda Easy, Matthew Shields, Celia Skinner, Celia Aitken2
In this sample HIV-2 infection and HIV 1and 2 co-infection are common. Ethnic origin is not necessarily a reliable marker of HIV-2 infection. PPA testing may give false positive reactions due to cross reactivity between HIV-1 and HIV-2 We recommend HIV-2 testing of all patients from sub-Saharan Africa.
A M Geretti, C McDonald, M Smith, P Easterbrook1, B Peters, K Ranjababu2, S Kegg, P Hay3
Our preliminary data indicate that in highly NRTIexperienced patients switching from stavudine to tenofovir in the context of a PI-based regimen is associated with maintained virological control despite the previous detection of mutations that are known to affect tenofovir susceptibility. However, patients on nevirapine appear to be at risk of virological rebound associated with the re-emergence of archived resistance mutations. Although M184V has been shown to restore tenofovir susceptibility in vitro, the addition of lamivudine in one patient improved virological control only transiently.
Christopher Payan1, Christine Brault, Marylin Peigne, Jocelyn Loison, Jean-Marie Chennebault2, Alain Esnault, Pascale Ogel3
In conclusion, the HIV LCx assay provides good viral load measures for all HIV-1 types, mostly for group O strains and allowed their therapeutic follow-up.
Preeyaporn Srasuebkul1, Chris Duncombe, Kiat Ruxrungtham, Chaiwat Ungsedhapand, Darl Bien, Praphan Phanuphak2, David A C Cooper3, Joep M A Lange4
Sharp blips, LLV and virological failure were significantly more frequent in the non-PI regimens. Higher baseline HIV-RNA was associated significantly with more frequent occurrence of blunt blips (p<0.01). Baseline CD4 count, HIV-RNA, CDC classification and patient gender did not predict the occurrence of sharp blips, LLV or failure. The occurrence and pattern of blips did not predict subsequent LLV or virological failure.
Heribert Knechten, Christian Hohn, Myong Ock Yun-Kremer, Patrick Braun, Robert Ehret, on behalf of the Naagno Study Group
In 2000 the preferred therapy was a PI containing regimen. In 2001 and 2002, most patients were successfully treated with a combination of 2 NRTI plus 1 NNRTI. This achievement may be due to the relative short availability of this substance-class. Regular monitoring of these data and a given feedback for each centre compared to the group should lead to improve quality management for medical centres.
Dmitriy Kosarikov, Robert Current, Karen Ding, Rashmi Kotadia, Nancy Low, Namneet Rudra, Rita Sun, Theresa Young
The non-clinical performance of the CAP/CA PHS/PHM, v1.5 match or exceed that of the CA HIM, v1.5. The CAP/CA PHS/PHM, v1.5 eliminates the result variability introduced by the operator’s technique and allows other laboratory activities to occur while the samples are being processed.
M Schmitt-Haendle, M Baeuerle, A Taubald, C Pfeiffer, T Nagel, B Manger, T Harrer1, B Schmidt, H Walter2
Despite a potent HAART plasma viral load could not be fully suppressed in this patient probably due to excess viral replication in the brain which could not be targeted sufficiently by the currently available drugs. At least in a minority of patients on HAART, residual HIV-1 replication in the brain of patients may cause neurological disease. Such patients need more potent antiviral drugs with a better CNS penetration than current antiretroviral drugs. CSF HIV-1 viral load should be examined in patients with persistent neurological symptoms on HAART.
Michael Miller, Dion Coakley, Andrew Cheng, Nicolas Margot, San Tran, Damian McColl
Among treatment-naïve patients, virologic failure to the regimen of TDF+3TC+EFV occurred in >10% of patients by week 48 (ITT) and was associated most frequently with EFV- and 3TC-associated mutations. The K65R mutation occurred in a slightly higher percentage of TDFthan d4T-treated patients and there was no evidence for other TDF resistance pathways. Good virologic outcome was achieved in patients who failed with K65R and other regimen-associated resistance mutations with the use of 2nd line therapy that included a PI.
D J McColl, Nicolas Margot, Andrew Cheng, Michael Miller1
Antiretroviral-treated patients (pts) with incomplete HIV RNA suppression are at risk for the development of resistance mutations from drugs in their regimen. Two large placebo-controlled trials evaluating tenofovir DF (TDF) as an addon therapy to failing antiretroviral regimens with incomplete HIV RNA suppression were analyzed for the development of resistance mutations.
Jacques Izopet, Patrice Massip1, Gilles Force2, Benedicte Delmas3, Herve Gallais4, Christian Aquilina5, Frederique David on behalf of the AZLF3003 study group6
To investigate the changes in resistance genotype and drug susceptibility after treatment interruption and assess the short term antiretroviral effect of a treatment regimen with trizivir (TZV) and efavirenz (EFV) following a shift from a drug-resistance genotype to a wild type (WT) genotype
Genotyping mutations associated with AZT resistance were seen in 20% of pregnant women with increasing prevalence during the observation period and an association with length of drug exposure. ARV resistance to multiple agents were rare among pregant women in this cohort. Continued surveillance is going on as is the analysis of genotyping and the subsequent clinical course among infected children.
Initial development of NN models resulted in successful training with a limited dataset and demonstrated the feasibility of this approach to predict absolute VL change, VL trajectory and virological failure from complex input variables. As the size of the training data set increases, it is anticipated that the accuracy of these predictions will also increase and that this technique will prove to be a useful tool for predicting treatment outcome from genotype.
A Winston, S Mandalia, D Pillay, B Gazzard, A Pozniak
3TC use is independently associated with a reduced incidence of losing NNRTI mutations and a higher incidence of gaining further NNRTI mutations. The presence of M184V may push viral evolution to select further development of NNRTI mutations.
Paola Cicconi, Marco Bongiovanni, Teresa Bini, Federica Tordato, Sara Melzi, Elisabetta Bulgheroni, Francesco Croce, Paola Citterio, Antonella D’arminio Monforte, Stefano Rusconi
In our clinical setting the use of LPV/RTV allowed for a substantial increase of CD4+ lymphocytes and a sustained decrease of plasma viremia; 2) Subjects with = 5 PI-related mutations at baseline showed a better virological outcome and a higher percentage of viral load undectability compared to patients with > 5 mutations – this was not mirrored by CD4+ counts; 3) We did not observe a qualitative difference of mutational profile in LPV/RTV responders compared to failures, in particular no single amino acid substitution has been found predictive of failure.
Michael Brady, Sarah Fidler, Simon Dunstan, John Clarke, Jonathan Weber1
The purpose of this study is to determine whether a short course of antiretroviral therapy (SCART) in primary HIV-1 infection (PHI) is associated with induction of new viral drug resistant mutations.
Leonardo Calza, Marco Borderi, Francesco Chiodo, Barbara Farneti, Livia Tampellini 1, Maria Carla Re, Paola Monari, Isabella Bon 2
In our HIV-infected population receiving a nelfinavir-based HAART, the D30N mutation has shown a low absolute frequency, while the detection of M184V substitution and the simultaneous occurrence of M184V, T215Y and K103N mutations were related to a more favourable virological response.
N C White, J N Weber, J R Clarke 1, D Israel-Biet 2
Despite differences in resistance associated mutations between HIV-1 quasi-species derived from the lung and peripheral blood RT, we found no evidence that this is attributed to the separate evolution of RT between the two compartments. However, separation of lung and blood quasi-species was detected in env Therefore it is evident that discordant resistance patterns between the lung and blood may be due to drug penetration, intracellular drug levels or phosphorylation of NRTIs, as opposed to independent evolution of HIV within the lung and blood compartments.
Others have demonstrated discordant RT mutations between HIV derived from peripheral blood and other compartments, including semen . This study has shown both genotypic and phenotypic differences in resistance to NRTIs in the lung and peripheral blood. These data suggest a role for the lung as a sanctuary site during antiretroviral therapy.
Ellen Fiss, Rachel Shahinian, Sherry Zhang, Nancy Schonbrunner, David Gelfand, Thomas Myers
The process of RT/PCR has become increasingly important in nucleic acid based diagnostics and molecular biology research in general. However, performing sensitive, long RT/PCR has remained a problematic and time-consuming procedure, especially in the clinical laboratory setting. We previously found that the implementation of an RT/PCR system using a mixture of thermostable DNA polymerases could alleviate many of the challenges of performing highly sensitive long RT/PCR.
L Celis, K De Smet, J Louwagie, P Segers, K De Boeck, A De Brauwer, H Pottel, F Hulstaert1, K Van Laethem2, M G Rizzo3, P Braun4, B Vanderborght5, J C Schmit6, D Hendricks, R Ziermann7
When used in combination with their respective interpretation algorithms, a relatively low level of discordance was observed between the number of drugs excluded by LIPA or sequencing, a level comparable to the one found between the two sequence-based algorithms. These results indicate that similar treatment-regimen decisions may be reached when using the LPA or DNA sequencing-based test systems.
Stefan Neifer1, Mathias Walter, Jurgen Kolzsch2, Gerda Siebert, Norbert GroƒÀmann3
Three different combinations of two NRTI's did not suppress the viral load below the detection limit of 400 copies/ml. This finding was associated with a high prevalence of nucleoside-resistance mutations. An increase of CD4+ lymphocytes was observed. The medical outcome of the treatment indicated in increase in life quality. The benefit of the therapy has to be discussed in context with the observed nucleoside-resistance mutations in the majority of these patients
Drug resistance is an important cause to failure of antiretroviral treatment. In patients with low but detectable viremia after an initial virological response, there is only a limited knowledge to which extent the low-level of viremia is sufficient to allow emergence of drug resistant viruses.
These results demonstrate that viruses containing M184V can retain some degree of sensitivity to 3TC, even when the latter is used at concentrations close to its IC50.
Our findings show that although LPV/r provides a high genetic barrier to the development of resistance, a substantial proportion (21%) of PIexperienced patients have already developed different levels of crossresistance to LPV/R. Development of resistance was more pronounced with patients treated with ritonavir. Administration of LPV/r thus, must be carefully assessed in ritonavir heavily pre-treated patients.
Carlo Federico Perno, Federica Forbici, Giuseppina Liuzzi, Patrizio De Longis, Mauro Zaccarelli, Ada Bertoli, Valerio Tozzi, Giampiero D’offizi, Andrea Antinori, Maria Paola Trotta, Maria Concetta Bellocchi, Pasquale Noto, Caterina Gori, Roberta D’arrigo, Enrico Girardi1, Andrea De Luca, Antonella Cingolani, Maria Gabriella Rizzo, Simona Di Giambenedetto, Francesco Baldini2
Dynamics of appearance/disappearance of M184V/I mutation is quick after 3TC failure/interruption, suggesting easiness of development of such mutation but also a remarkable growth-disadvantage for HIV. From the clinical perspective, recycling of drugs whose antiviral activity is affected by M184V mutation can be successful after appropriate drug wash-out, also in heavily pre-treated patients.
Mark Oette1, Rolf Kaiser, Martin Däumer, Dieter Häussinger2, Klaus Göbels, Christoph Vogt, Dariush Akbari, Arne Kroidl, Matthias Wettstein3
HAART-naïve HIV-patients harbour primary resistant virus in 10.3 % and revertant variants in 2.9 %. Both types of mutations are associated with reduced efficacy of HAART in several studies. These results are of significant clinical relevance because of limitation of treatment options in affected persons. Altogether, the prevalence of drug resistant HIV is 13.2 % in this part of Germany. The majority of these cases accounts for NRTI-associated resistance. Thus, routine genotypic resistance testing in untreated HIV-positive patients should be performed before administration of first-line HAART.
Rodger Macarthur, Lawrence Crane, Martha Farrough1
The nelfinavir (NFV)-selected D30N mutation results in resistance to NFV only, whereas the NFV-selected L90M mutation is linked with resistance to multiple PIs. We studied the efficacy of NFV and the incidence of D30N, L90M, and other mutations that occur when NFV was used as part of an initial regimen of highly active antiretroviral therapy (HAART) among a predominantly indigent population.
X-W Shao1, A Malmsten2, J Lennerstrand, A Sönnerborg3, T Unge4, J S Gronowitz, C Källander5
The drug susceptibility profiles of the RTs recovered directly from plasma correlated well with occurrence of mutations known to be associated with drug resistance. The method provides a simple and rapid alternative for analyzing phenotypic drug susceptibility.
Elisabetta Bulgheroni, Paola Citterio, Francesco Croce, Mirko Lo Cicero, Massimo Galli, Stefano Rusconi1, T-C Chou2
1) Our in vitro combination studies showed that PI-resistant isolates were 3.95- to 48.5-fold less susceptible to PIs than 14aPre; 2) TPV+APV and LPV+APV seemed to be more active against drug-resistant isolates probably due to maximally suppressive concentrations of single PIs; 3) the different efficacy between TPV+APV/LPV+APV/TPV+LPV could be due to the competition between the compounds within the protease catalytic site.
Michael Burke, Israel Yust, Yael Sela, Irene Zeldis, Ben Werner, Agnetta Skibin,Vera Zacut, Nurit Vardinon
We recently described the intracellular viral HIV RNA assay (ICVRNA), using peripheral blood mononuclear cells, as a possibly useful parameter in assessing HIV positive patients on HAART with low or undetectable plasma viral loads (PVL). We now investigate the role of ICVRNA as a predictor of viral resistance.
Franco Maggiolo, Annapaola Callegaro, Gianpaolo Quinzan, Claudio Arici, Giampietro Gregis, Diego Ripamonti, Antonio Goglio, Fredy Suter1
The concern about cross-resistance induced by thymidine-associated mutations (TAMs) has raised the question about the risk of using thymidine analogues as first line antiretroviral agents.
The dissimilar trends in resistance between the different categories of drugs may reflect differences in the use of drugs with time; resistance to PIs and NRTIs remained stable, or has been decreased, respectively, in contrast to NNRTIs, which were gradually increased in HAART regimens after year 1999. The prevalence of the MCR isolates remained roughly stable in years 2000 and 2001 suggesting thus, that the proportion of patients with limited therapeutic options did not change within the study period.
Resistance testing in HIV patients is an increasingly common tool to optimise the efficacy of antiretroviral medication. British HIV Association (BHIVA) guidelines make recommendations on the use of this test in HIV management. We examined the use of this test in our patient cohort.
Elke Lauenroth-Mai, Frank Schlote, Christoph Schuler1
HAART regimens containing the traditional backbone of at least two nucleoside analogues are limited by adverse events, long-term toxicity and the development of viral resistance and cross-resistance within the NRTI class, particularly in patients who have previously undergone prolonged NRTI exposure. In contrast, high plasma levels of two potent protease inhibitors may be able to overcome underlying PI-associated drug resistance.
A-M Lucas, A Burke, S A Newland, B A Larder, S Kemp1, L Ruiz, A Bonjoch, J Martinez-Picado, B Clotet2
Using a new prototype CLIP sequencing assay, this study identified mutations in a highly conserved region of HIV-1 gp41 that were associated with decreased sensitivity to T-20, among patients in a clinical trial. Following further validation, this assay should be a useful tool for monitoring resistance to fusion inhibitors.
Our preliminary results on a population of HIV-1 patients pre-treated with no more than 6 drugs, failed to show any significant short-term differences between genotype or phenotype testing for patients with virological failure for whom a new HAART regimen was chosen.
In conclusion, the occurrence of the specific nelfinavir genotypic resistance profile is infrequent among both nelfinavir-naïve and nelfinavir-experienced patients. Cross-resistance between nelfinavrir and other protease inhibitors may be limited also in patients who experienced prior long-term antiretroviral therapy, from second-line to rescue regimens, provided that they were pre-treated with drugs other than nelfinavir.
S Hillebrand, F D Goebel, B Banas1, O Postea, N Weiss2, M Keller, F Krötz3
Incubation of EC with antiretroviral drugs changes their phenotype in a way that leads to increased MO adhesion. This might promote atherosclerotic lesion development and progression. As the classical adhesion molecules are not upregulated and as no activation of NF-κB could be found, these drugs may activate EC via an alternative, NF-κB independent, pathway. As indinavir increases superoxide radical production in EC, alternative, redox-sensitive pathways may be involved in the activation of EC exposed to antiretroviral drugs.
C Payan, M Riou1, G Renier, H Le Guillou2, P Fialaire, J Loison, J M Chennebault3
In conclusion, this anti-HIV avidity measurement could be used to assess the functional activity of CD4 cells restoration in HIV-infected patients with viral response under HAART.
Vassilis Vigklis, Alexandra Siorenta, C Michailidis, M Lelekis, Sofia Boti, Maria Chini, Violetta Karachaliou, J Stephanou, P Gargalianos
The increase of viral load leads to strong activation of circulating CD8 lymphocytes resulting in increased CD38 ABC expression. The high correlation between viral load and CD38 ABC on CD8 as well as their subpopulations and the high proportion of CD8+ cells and their subpopulations that express more than 12,000 CD38 molecules per cell, shows that CD8 T cell activation determined by viral load reflect a separate pathogenic component of HIV-1 disease.
V Vigklis, M. Spiropoulou-Vlachou, S. Boti, A. Siorenta, M. Papadimitropoulos, M. Lelekis, C. Stavropoulos, P. Gargalianos1, G. Saroglou2
1) The viral replication in patients with higher viral load is probably required to maintain higher frequencies of Ag specific CD8+ T cells. 2) The lower proportion of CD8+pol+ cells may reflect fewer reverse transcriptase epitopes than gag.
(iv) In contrast to previous concepts of either B-cell or combined B- and T-cell defects in CVID, these observations suggest a key role of the CD4 cell in the pathogenesis of CVID prompting further research on the role of CD4 cells in the pathogenesis and for potential therapeutic approaches in CVID.
G D Panayiotakopoulos, A N Kontos, H M Moutsopoulos, T Kordossis1, K Aroni2, D Kyriaki3, S Paikos4, N Vouyioukas, A Vlachos5
The prevalence of DILS in compliant patients on HAART is 0, in contrast with our previous study performed in the pro – HAART era (1994 – 1995) which was found to be 7.8% [3]. The HAART brings major reductions in viral load and increases in CD4 T cell counts and seems to influence positively the autoimmune phenomena associated with HIV infection.
S Horster, C Jung, C Zietz, JR Bogner, M Siebeck, FD Goebel
These findings may suggest that either plasmablastic NHL was already present in the spleen or the subsequently diagnosed NHL represents a leukemic course of MCD. Plasmablastic cells may represent a monophenotypic but not necessarily a monoclonal population. So far it is not known whether PL is due to a monophenotypic expansion or a true transformation of MCD cells. Furthermore splenectomy for MCD and immediate treatment of PL resulted in a significant survival benefit in our patient.
Roberto Manfredi, Leonardo Calza, Francesco Chiodo
In conclusion, a relationship between morphological and functional activity of thymus is confirmed in HIV-infected adult patients. Further studies including subjects with HIV disease and a blunted immune recovery or a discordant response to antiretroviral therapy are strongly warranted.
David Chadwick1, 3, Jeffery Pido-Lopez, Antonio Pires, Nesrina Imami, Frances Gotch2, Nicholas Paton3
Whilst thymosin a1 does not appear to induce more rapid recoveries of CD4 counts in patients with advanced HIV infection and suppressed viral loads on HAART, the significance of the increase in TREC levels, possibly indicating stimulation of thymopoiesis, remains to be determined. A larger trial with clinical endpoints would be required to answer this question.
Emil Toma, Maude Loignon, Louise Labrecque, Cecile Tremblay, Lise Cyr, Marie Cordeau, Raymond Beaulieu1, Don Zarowny, Anona Thorne2, Nicole Bernard3, Tanweer Sindhu, Jose Menezes4
This approach led to a high ARS incidence (spontaneously resolved) followed by partial containment of viremia, long periods off ART, improvement in HIV-specific and Th-1 type immune responses.
D Mildvan1, M King, K Real, R l Tressler, B Bernstein, E Sun2, J Feinberg3, G Beall4, J Eron5, F Carpio-Cedraro6, H Horowitz7, D Wheeler8, H Kessler9, P Ruane10, B Yangco11
Change from BL to wk 48 in CD4 count was negatively correlated with wk 48 CD4 activation (r=.0.41, p=0.02) but not CD8 activation (r=.0.21, p=0.24). Subjects with VL<50 and <50 c/ml at wk 48 had similar mean CD4 activation at wk 48 (8% [n=5] and 7% [n=28], respectively), but subjects with VL<50 c/ml had higher wk 48 mean CD8 activation (19% vs. 11%, p=0.01). In summary, the proportion of CD4 and CD8 activated cells decreased from BL to wk 48, while naïve and memory CD4 and naïve CD8 cells increased. CD8 activation markers appeared to be increased in subjects with VL>50 c/ml and CD4 activation was higher in subjects with lower CD4 cell increases through wk 48.
E Pujol, E Canas, F Jimenez-Onate, A Dominguez, J M Kindelan, J Santos, E Cruz, J E Corzo, J Benitez, M A Lopez-Ruz, M C Galvez, M Gonzalez
The prevalence of tuberculosis is high in our HIV-infected population (21.5%). The use of antituberculosis drugs has decreased in recent years, suggesting a fall in the incidence of active disease.
Michael Baeuerle, Matthias Schmitt-Haendle, Peter Löw, Thomas Harrer
In this patient with progressive KS despite potent HAART therapy with IL-2 showed significant activity against KS. Due to the high costs of liposomal anthracyclines, therapy with IL-2 was associated with substantial cost savings. Further studies are needed to evaluate the efficacy of IL-2 in the treatment of patients with KS.
In summary, the emerging spectrum of gram+ and gram- bacteria was compared in a large cohort of HIV- and HIV+ individuals. The pattern of emerging MRSA clearly increased in HIV+ and HIV- during 1995–2000 accounting for up to 24.8% of MRSA in HIV sputa and 16.7% of skin swabs of HIV+ whereas MRSA has only increased in the last year in HIV- for up to 15.5%. While the sensitivity of SA coagulase-negative staphylococci to imipenem and piperacillin/tazobactam was preserved throughout the last 4 years ciprofloxacin can not be recommended as a first-line antibiotic against staphylococci.
Cristina Gervasoni, Massimo Galli, Anna Lisa Ridolfo, Antonella d’Arminio Monforte, Mauro Vaccarezza, Anna Cappelletti
In the 1997/2000 cohort no cases were observed during the follow-up. TMA is associated with conditions observed in the advanced phases of HIV infection. The disappearance of TMA during HAART may be explained by the reduction of the percentage of patients with long-lasting CD4+T cell depletion, advanced AIDS, cryptosporidiosis and multiple chemotherapy courses for cancer treatment.
Bruno Malafronte, Isabelle Perbost, Pierre Dellamonica
Patients that came quite late for treatment during an OI are nonetheless able to adhere very effectively to a follow-up and to the cures for their seropositivity. Conversely, pre-treated patients show a death rate signifi- cantly superior to 29 months that could be a consequence of their more difficult compliance.
Alison Currie, Neena Bodasing, Andrew Winter, Ysobel Gourlay, Dermot Kennedy
In HIV infection, syphilis can progress more rapidly through each of the clinical stages and will often have an atypical presentation. Respiratory manifestations have been described infrequently [1,2]. We present a patient with secondary syphilis who had presented with respiratory symptoms.
Mycobacterium kansasii infection occured late in the course of HIV disease and was associated with advanced immunosuppression. Extrapulmonary infection is rare. This is the first report of ocular involvement.
Leonardo Lourtau, Javier Toibaro, Adriana Duran, Claudio Gonzalez, Cesar Saenz, Marcelo Losso
These preliminary data suggest that concomitant treatment of HIV with ritonavir/saquinavir based regimen and TB treatment including rifampin was well tolerated and could be an option in settings, where rifabutin is not available. Prolonged follow-up is needed to analyse impact of efficacy.
Maria Ale-Castro, Jose Castro1, Miguel Goicoechea2
In conclusion, in this population, disseminated tuberculosis affected mainly middle-aged, institutionalized patients from racial minorities with advanced HIV infection, and frequently was the initial manifestation of HIV infection. Incidence of drug resistant bacilli was a particular problem in this setting.
Francesca Conradie, Ian Sanne, Prudence Ive, Willem Venter
Paradoxical TB reactions can present with a fulminant presentation. This potentially fatal condition can be detected by measuring a temperature 2 to 8 weeks after initiating HAART. In a high TB incidence area, all patients should be seen at 4 weeks after starting HAART for a physical examination including a temperature measurement. Incomplete TB treatment may predispose to the syndrome. CXR before HAART does not exclude the diagnosis.
At 24 months follow-up he has remained well and is maintained on 100mg fluconazole and HAART. VL is undetectable and CSF has been negative for cryptococcal antigen by latex agglutination and monoclonal antibody ELISA. Var. gattii is predominantly an infection of the immunocompetent in tropical regions and is more likely to form mass lesions in the CNS and to resist anti-fungal therapies. The development of hydrocephalus and the need for prolonged and aggressive antifungal therapy is characteristic of infection with this serotype. Even in areas where C. n. var. gattii does not exist, this infection should be considered as a travel-related infection in HIV-positive patients.
Caroline Boulouffe, Geneviéve Derue, Bénédicte Quivron, Herbert Rooijackers, Frédéric Frippiat
This case illustrates that, at least in late onset of EIP complicating CM in AIDS patients, a medical treatment could be proposed in order to avoid neurosurgery.
Christina Thirlwell, J Stebbing, M Nelson, B Gazzard, M Bower
Treatment of AIDS-related NHL with CDE and HAART is associated with a median OS of greater than 1 year. This compares favourably with our previous regimens used in the pre-HAART era (see Table). The survival correlates with NHL related factors (IPI index) rather than HIV-associated factors (CD4 cell count or viral load).
F Rodriguez-Gomez, J Borrero, J Garcia, D Merino, F Cuesta, Pujol de la Llave
VIH infection dramatically increases the risk of developing non-Hodgkin’s lymphoma (NHL). Plasmablastic lymphoma (PL) is a rare and particular type of AIDS-related NHL presenting in the oral cavity and jaws. We report two cases of PL: an oral PL and other presenting with lymphadenopathy and bone marrow involvement, without oral lesion.
D Baylis, N Lubis, A Short1, J Stebbing, A Teague, S Portsmouth, M Bower, M Nelson, B Gazzard2
These data are consistent with an influence of climatic conditions on the presentation of PCP. The diagnosis of PCP is more common in winter months suggesting that this is a transmissible infection.
T Prestileo, F Di Lorenzo, E R Dalle Nogare, A Columba
In AIDS patients treated with highly active antiretroviral therapy (HAART), CDV is tolerated and efficacy to control of CMV replication, with improved clinical outcome. However, additional studies are needed for a better use of this drug.
Primary pulmonary hypertension is a serious illness, most commonly presenting in females in the third and fourth decades. Its incidence is two cases per million inhabitants, but in HIV-infected patients is probably much more common than in the general population. Recently a few patients with this condition have been reported who have improved with antiretroviral treatment.
Roberto Manfredi, Leonardo Calza, Francesco Chiodo
The introduction of HAART determined a profound modification of the natural history of HIV disease since the year 1996, especially after a sharp drop of the large majority of opportunistic disorders related to a severe HIV-related immunodeficiency. A prolonged survival and the persisting of an important alteration of immune system response, extended to the cytokine and cell network responsible for the control of neoplastic diseases, led to observe a proportionally increased incidence of cancer among HIVinfected patients, extended beyond AIDS-defining neoplasms. The occurrence of a dual AIDS-associated neoplastic disease is an extremely rare event as to international literature data, but it may become an increasing concern in the future, given the notable increase of life expectancy of patients treated with HAART, and the persisting of supporting immunopathologic conditions. A persistent HIV-associated immunodeficiency and an incomplete
virological response to HAART were shared by both cases recently observed in our patient cohort.
Annette Stelzer, Klaus Göbels, Torsten Feldt, Mark Oette, Stefan Vom Dahl, Dieter Häussinger1
Gastrointestinal diseases are a frequent problem of HIV patients with a low CD4 count. Invasive diagnostic procedures like endoscopy is frequently necessary for diagnosis. The objective of our study was to evaluate the diagnostic yield of the Given® Video Capsule System (Given Imaging, Yoqneam, Israel) in HIV-linfected patients and its therapeutic implications.
C. Ribeiro, Emilia Valadas, Nancy Faria, Sandra Felisberto, Robert Badura, Isabel Henriques, Francisco Antunes
In late stage HIV-disease it is often difficult to define a single cause of death and it remains often unclear if the working diagnosis and treatment strategies were the most appropriate. Consequently, data from autopsies are important for a better understanding of the spectrum of HIVrelated infections/diseases that ultimately lead to death. Even if a complete necropsy is not possible, a partial autopsy (e.g. needle-biopsy), especially of the brain, could establish a final diagnosis.
Jose Castro, Miguel Goicoechea1, Maria Ale-Castro, Roberto Monroig2
In this cohort of patients, disease caused by MAC in individuals recently started on ART had a distinct clinical presentation. It presented within the first months of initiation of ART in patients with low baseline CD4+ counts, and was characterized by localized disease. Additionally, this form of MAC presentation occurred in those patients with a virologic response to ART and had a favourable prognosis.
Klaus Göbels, Torsten Feldt, Mark Oette, Joachim Richter, Dieter Häussinger1, Martin P Grobusch2, Mario Sarbia3
It is important to include visceral leishmaniasis in the differential diagnosis, especially in HIV patients with relapsing fever and pancytonenia, who have travelled to the Mediterranean basin or the tropics. Despite adequate treatment and a good initial response, relapse rates in HIV-infected patients can be as high a 70%. Follow-up investigations are essential to detect any signs of relapse.
Marina Núñez, Beatriz Díaz, Mayte Pérez-Olmeda, Pilar Ríos, Juan González-Lahoz, Vincent Soriano
3TC-containing HAART regimens had a positive impact on the course of HBV infection in HIV-infected patients, achieving a significant decrease in HBV-DNA levels in the majority. However, complete cure of the infection was achieved only in a minority of subjects. The HBV developed 3TC resistance mutations in more than half of patients experiencing HBV-DNA breakthrough over time.
This case highlights the fact that individuals co-infected with HBV, and in whom HbcAb and HbsAb antibodies have developed can have a reactivation of, or possibly re-infection with a different strain of, HBV. This case suggests that tenofovir monotherapy may be sufficient to clear HBV infection in HIV and non HIV infected individuals.
M Geit, J Aubock1, R Hubmann, G Biesenbach2F Muhlbacher, R Steininger3, FWutzelhofer4
Patients co-infected with HIV/HCV have a faster progression of liver disease. In the last years liver transplantation has been discussed and is indicated in selected cases with suppressed HIV viremia. Albumin dialysis is helpful in cholestatic hepatitis as shown in this case.
S Portsmouth, G Matthews, M Atkins, M Bower, B Gazzard, M Nelson1, J Stebbing, A Barr2, M Fisher3
These results indicate that 24 weeks of tenofovir in addition to anti-retroviral therapy is active against hepatitis B, and appears to overcome lamivudine resistance.
Pedro Cahn1, Peter Piliero2, Michael Giordano, Alexandra Thiry, Steven Schnittman3
HIV and hepatitis B and C virus (HBV, HCV) have similar modes of transmission. Coinfection with HIV and HBV and/or HCV is common. In coinfected patients, underlying hepatic pathology from HBV or HCV may complicate HIV treatment. Atazanavir (ATV) is a potent, safe, and effective once-daily protease inhibitor that rapidly and durably suppresses HIV RNA and durably increases CD4. Clinical trial BMS-008 evaluated safety and efficacy of ATV (400, 600 mg) QD over 48 weeks vs nelfinavir (NFV, 1,250 mg) BID, each with d4T+3TC in antiretroviral-naïve subjects. This analysis evaluates changes in HIV RNA and hepatic transaminases through week 48 in HBV and/or HCV-positive (+) and -negative (–) subjects. HBV and/or HCV (+) and (–) subjects had similar HIV RNA suppression through week 48. HBV and/or HCV (+) subjects had more hepatic transaminase elevations (Grade 1 to 4) than did (–) subjects. These elevations were comparable to those in the NFV treatment group.
Esther Voigt, Christian Schulz, Juergen K Rockstroh1, Stefan Mauss2, Gerd Klausen, Joachim Golz3, Elke Lauenroth-Mai4, Franz A Mosthaf5
Peg INF plus RBV shows better antiviral efficacy than conventional (nonpegylated) INF-α plus RBV in HIV/HCV co-infected. Overall, discontinuation rate is low. However, psychiatric disorders are a major problem in this cohort with a high proportion of former drug users.
R Browne, D Asboe, Y Gilleece, S Mandalia, M Atkins, B Gazzard, M Nelson1
It has been reported that men who have sex with men are at increased risk of hepatitis C partially due to sexual transmission. With the increasing levels of sexually transmitted infections in this group we have identified incident cases of hepatitis C to explore whether infection rates are changing and to further define risk factors of acquisition.
Our results suggested that the association therapy IFN+ribavirin dramatically increases sustained virological response in HIV-positive patients. Interestingly, ETR patients (prevalently treated with IFN alone), and SR patients showed a higher rate of mutations in ISDR region as compared to NR patients, p=0.043. The wild-type ISDR profile was prevalently found in NR patients. Finally, the pretreatment number of mutations was not associated to immunological status of HIV-positive patients.
Anna De Bona, Giovanni Sitia, Caterina Uberti-Foppa, Laura Galli, Donatella Ciuffreda, Giulia Gallotta, Adriano Lazzarin
All multivariate models calculated to test if liver histopathology (Ishak grading or staging) between HIV/HCV-coinfected patients versus HCV-monoinfected or antiretroviral-treated versus untreated subjects did not show any difference.
In the era of HAART, the first cause of death in patients with HIV infection is cirrhosis of the liver. Inadequate treatment is common among patients who die.
M H Haverkamp, M C A Smit, A J L Weersink, C A B Boucher, I M Hoepelman
This is the first report on a CD4 depending HBV response with 3TC therapy in a small cohort of patients. Large prospective studies are necessary to investigate this further.
The D4T-ribavirin association seems to be safe in our study. As regard of the seriousness of acute pancreatitis, it’s not recommended to use DDI in association with ribavirin particularly in cases of long exposure with this drug.
Erica Peters, Ysobel Gourlay, Andrew Seaton, Roger Wong, Sheila Eves, Ray Fox1, Sheila Cameron2
In conclusion, HCV can successfully be treated with Peg-INF and RBV in patients coinfected with HCV and HIV. Adverse events are more common, but can be managed without necessitating withdrawal of treatment. Regular clinical input and a multidisciplinary approach contribute to the management of adverse events and adherence to therapy.
ESLD mortality appears to have increased since 1998 in this cohort with poor uptake of HART. This is different from other cohorts where greater than 50% of these liver deaths had CD4+ counts of greater than 200, and non-detectable plasma HIV RNA levels in the six months before death. There is no statistical significance however between the survival of HAART and no HAART patients and those with heavy alcohol intakes compared with no/low alcohol intakes.
Gerlinde Michl, Josef Eberle, Ingo Westner, Johannes R Bogner, Frank-D Goebel
Repeated flares might be a positive prognostic parameter for HBsAg/anti- HBs seroconversion. HAART containing 3TC seem to be supportive. Studies in HIV/HBV-coinfected patients should further explore 3TC as a component of HAART.
TB preventive therapy (TBPF) for persons with HIV infection is potentially one of the most useful measures available. A study conducted by the TB Control Programme and TASO in Uganda, 2000, showed that it was effective in preventing the development of active TB and delayed the progression to HIV disease and even death. WHO and other bodies have called for further research into preventive therapy, yet questions have been raised about the economics and feasibility of TBPT.
The purpose of this survey was to study the prescription tendencies of the clinicians regarding ARVs in Zambia. This was acheived by accompanying pharmaceutical sales representatives to chemist shops and private clinics and by monitoring the prescription habits of doctors treating HIV patients and recording the various combinations of ARV's used by clinicians and those sold by drug stores to patients.
Despite the reduction in cost of ARVs, it has been observed that PLHA still do not have access to the drugs in resource poor setting like Nigeria. Since research has shown that high level of HAART are required to achieve sustained suppression of viral replication.
Proper patient selection, modifying ARV, appropriate dose reduction, combo-ARVs and increasing follow-up intervals improves access. Our patients need not be in despair, thanks to generics and HU that western researchers and governments ignored under pressure from powerful pharma lobby. Despite low cost PI-free regime, results were similar. Mean monthly cost for Gr.A is $150, B is $30, C is $22. Availability of generics is a boon and even patented drugs prices were reduced. Preferential pricing and compulsory licensing can increase the access.
Martin Schutten, Bert Niesters, Ab Osterhaus, Ineke van der Ende1, Kees Brinkman2, Jan Prins3, Monique Keuter4, Jan Veenstra5, Sven Danner6
Relatively high percentages of the HIV-positive population in West Africa are infected with HIV-2. Knowledge of effective ART regimens against HIV-2 is therefore important for introduction of ART in West African countries. We set out to investigate the efficacy of AZT, 3TC, IDV, RTV against HIV-2.
It was decided to do a pilot study evaluating the annual cost of standard antiretroviral therapy versus annual cost of treating HIV-related opportunistic infections (OIs) in Kampala, Uganda, considering consequent morbidity and mortality in both public and private hospitals/nursing home settings.
N Kumarasamy, P Balakrishnan, T Yepthomi, A Kalamalini, R Rubavathy, A Priya Christy Bai, K G Murugavel, S Solomon1, K Mayer, T Flanigan2
Antiretroviral therapy with Indian generic drugs in advanced HIV positive patients appears beneficial in increasing CD4 cell count and TLC, and reducing OIs. High co-prevalence of TB must alert clinicians to immune reconstitution syndrome. The development of ARV therapy programs in developing countries is feasible.
NM Samuel, Jacob S Mini, S Parameshwari, V Vijayakumari
This pilot study demonstrates that supervised domiciliary ARV therapy is feasible, acceptable and efficacious in rural India with limited resources. Two patients who shared the antiretroviral drugs with their husbands suggest that continuous counselling need to be imparted that includes drug resistance and to consider offering ART to all infected in the family. It is evident that emergency services need to be provided at base hospital to treat the adverse effects of ARV drugs. Our dream to link prevention with care seems to work in Namakkal.
Community and home support is an important component of successful long term drug compliance especially in rural settings of developing countries which have limited monitoring structures.
Research on use of microbicides should be promoted in developing countries like Uganda where over 52% of HIV prevalence are women compared to 48% among men. Men should be sensitised on their existence to reduce fears about their female partners using them.
These data provide evidence that remarkable part of HIV-infected persons suffer from co-infection with HCV and/or HBV, as well as drug abuse. Financial resources of the majority of the patients are not able to cover HAART and treatment of blood-born viral hepatitis. Consequently the above-named facts as well as social status of the HIVinfected persons are impeding access to lifesaving treatment and/or limiting its effectiveness.
R Rayapu, K A Ramaiah, R Anand, J V Ramaiah, P B Satish, S Ramola, R Sarath
There is a dire need to educate and counsel the victims of the disease about the use of the drugs, complications and nutritious food in-take before the administration of the drug therapy.
R Sangamalla, R Ramesh Babu, R K Ayodhya, P Satish Babu, B S Rani, R V Kumari
“MEAN” a special package with zidovudine for PLW HIV/AIDS is very essential in countries like India. It affects the victims in the most positive way, meeting their nutritional needs, strengthening their bodies and improving the quality of their life.
Risk factors that predict early death in first world patients, were unhelpful in our population. More sophisticated markers of outcome, like CD4 counts and cryptococcal antigen titres are beyond our economic reach.
The evolution of tuberculosis cases was worse among patients with HIV infection. The frequency of treatment abandon was significantly higher among them. Such results alert to the need of paying attention to those patients’ treatments and to the need of studying the causes of these occurrences more deeply.
The occurrence of TB cases reported for the first time (not including re-treatment) decreased from 309 in 1999 to 142 in 2000 and to 96 in 2001 (a decreasing rate of 54% and 32.5% respectively in 1999 and 2000). In 2001, however, we verified an increase of 19.8% in the number of cases (115) in relation to the previous year. For 367 for whom it was possible to perform an antibiogram test, we found resistance to at least one drug in 60 (16.4). Further more, resistance rate increased from 12.6% in 1997 to 21.5% in 2001; concurrently, while multi-drug resistant strains represented 54.5% of resistant strains in 1997, in 2001 there were 71.4% of them. As to the outcome of treatment of 917 patients (from 1997 to 1999) from whom it was possible to analyse data, we found a cure rate of 40.7% and death during treatment rate 24.8%. When we analysed patients with resistant strains and those with sensitive strains (242 cases with available data), the cure rates were of 9.5% and 43.5% and death during treatment of 26.2% and 15.5%, respectively for both groups. After including protease inhibitors in the anti-retroviral scheme, at the end of 1999 in Mulago Government Hospital (TB Clinic), we noticed improvement in some indicators as a decrease in opportunistic infections like TB. If on one side our data reflects an improvement in diagnosis on the other side, it shows that we need a great commitment of TB and AIDS programs to improve cure rates and diminish resistance rates.
Dattatray Saple1, Satish Vaidya2, Ravi Vadrevu3, Ved Pandey4, Jitender Ramnani5
Strong political will for adequate training of prescribers and laboratory support is essential along with social system to assist the patient to adhere to drug therapy to prevent development of treatment failure and drug resistance.
As the cure rate (56 out of 72 = 15%) of oral candidiasis with itraconazole capsules 200 mg daily for 15 days is convincing, this may be chosen as the treatment for oral candidiasis, which is one of the most common opportunistic infections in the HIV population.
Causes of TB treatment defaulting in poor resource settings are multi factorial, the most important of which being poor counseling on compliance, societal stigma discrimination and denial of TB patients, lower accessibility of heath facilities as well as poor service provider attitudes. These need to be addressed in current and future TB and HIV/AIDS programs.
At the beginning, positive children were sickly, resented their care takers and weighed between 10kgs – 30kgs. At the end of the intervention, they rarely fell sick, weighed up to 20kgs – 50kgs, coped with living with HIV/ AIDS with a smile and lived a normal child’s life (e.g. going to school.) Integrated drug therapy, counselling and psychosocial support greatly improves the quality of life of HIV-positive children in Uganda.
From the above we can conclude that it is important for manufacturers / drug companies to take into account formulation and taste of pediatric ARVS to ensure success and adherence to the therapy. Parents and guardians should be counseled as to the importance of complying with the given regimen to ensure success. Addressing the community response and other interruptions during ARV administration to children can lead to success of this therapy in children.
We have registered many adverse events in treated infected-HIV children but they were of minor or mild clinical importance. There were no lethal risk reactions of ARV drugs. The treatment offer HIV-infected children a better quality and a longer life. The association of ARV chosen for every child as an individual provides a successful therapy.
Providing adherence support for children and families with HIV is often complex and professionally challenging. HIV is moving towards the status of a chronic manageable illness, and also the fact that most previous research has been adult based therefore, further research and audit within this field is much needed in Uganda.
Aurélie Fischer, Cyrille Lejczak, Christine Lambert, Guy Weber, François Schneider1, Jean Servais, Etienna Karita2 Thérèse Staub, Robert Hemmer, Jean-Claude Schmit, Vic Arendt3
Dried blood spots (DBS) on filter paper facilitate the collection, transport and storage of blood samples for laboratory use. The aim of this work was to develop an efficient DNA extraction from DBS for the PCR diagnosis of HIV infection in children born to infected mothers, and to compare the Amplicor HIV-1 DNA test version 1.5 (Roche Molecular Systems) with an in-house nested PCR.
Objectives To study and evaluate the effectiveness of combination antiretroviral therapy (ART) administered during pregnancy and its effects on infants.
Ben Werner, Israel Yust, Nurit Vardinon, Michael Burke
AZT protocols implemented to pregnant HIV positive mothers and babies reduces MCT of HIV to low levels in the developed world. However, the risk of AZT-induced hematological toxicity, especially in uninfected children, has not been adequately highlighted in updated guidelines. We studied the occurrence of anemia and neutropenia during AZT prophylaxis in newborns to HIV positive mothers during 1996-2002.
Our experience has highlighted a significant number of HIV-sero-discordant couples detected by routine antenatal HIV testing. We have noted that the psychosocial impact of a new antenatal HIV diagnosis can affect decisions concerning partner disclosure, treatment choices and psychological adjustment.
Information and data on patients and center were collected from March 1998 to June 2002 in Nigeria. These included demographic, preventive strategies at/by center, ARV drug history, availability of HIV pre and posttest and other counseling, and breast-feeding practices.
Acceptability of VCT by pregnant women is critical in the context of trials assessing interventions to reduce mother-to-child transmission (MTCT) of HIV. We studied the logistics and uptake of short-course oral AZT regimen by HIV-infected pregnant women after VCT in urban Uganda.
Elisabetta Chiesa, Dolores Repetto, Sara Melzi, Barbara Castelnuovo, Marco Bongiovanni, Paola Cicconi, Frederica Tordato, Teresa Bini, Antonella d'Armino-Monforte1, Elena Angeli, Barbara Argenteri2, Marco Mannazzu3, Francesco Di Candilo4, Nicoletta Dorigoni5
The aim was to describe the use of ART in a cohort of pregnant women in Italy, its effects on maternal infection and pregnancy outcomes and infant outcome and toxicity.
Since January 1998, 105 HIV infected women attending our antenatal clinic were enrolled at 18 - 24 weeks gestation in an HIV MTCT cohort. After counseling with informed consent, the women were given 100mg ZVD 4 times a day starting at 36 weeks gestation followed by 300mg orally at onset of labour, 300mg orally every 3hrs until delivery and no ZVD to infants. Infants with at least two consecutive positive PCR over a period of 13 months average were considered HIV infected. The probability of HIV infection to the infants was determined with Kaplan-Meier method.
The aim of the study was to evaluate the rate of vertical HIV transmission in Poland after introducing prophylactic strategies. Poland issued 3-part zidovudine prophylactic regimen in September 1994. Since September 1994 to June 2002, 160 children born to HIV-positive mothers were observed, including 95 who received prophylactic regimens.
Effective interventions to prevent and reduce mother to child transmission are currently available. A pragmatic and efficacious intervention is necessaary to reduce HIV transmission not only in intrauterine and intrapartum periods but during breast feeding period.
Every year in Uganda around 40,000 babies get HIV infection. The Ministry of Health started to implement a prevention of mother-to-child transmission (PMTCT) service free of charge from January 2000. At present, five (5) sites are operational. Monitoring and evaluation of program performance inter-site comparison, assessment and discussion of major problems faced.
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