This double issue of HTB has arrived slightly later than usual in order to include reports from the Lipodystrophy Workshop held in Dublin at the end of November, together with early reports from the EACS conference that followed afterwards.
This annual workshop – linked in alternate years to either the EACS or ICAAC conferences in Europe and the US respectively - provides an opportunity for clinicians, researchers, industry and community advocates to focus on side effects, especially those associated with lipodystrophy and metabolic complications. Although there were no dramatic breakthroughs at this meeting, a few studies had interesting implications for clinical practice and these are reported below.
Immediately prior to the Lipodystrophy Workshop, the Forum for Collaborative HIV Research (FCHR) organised a roundtable discussion to focus on side effects in resource-limited settings. A report from this meeting was included in the programme of the main Workshop, and was given by Veronica Miller, the director of the Forum.
Two years ago at the Lipodystrophy Workshop, Ulrich Walker presented in vitro data that supported uridine supplementation to reduce or reverse lipoatrophy induced by thymidine analogue associated mitochondrial toxicity. Last years Workshop saw further in vitro data. There was therefore considerable interest in the first in vivo results, presented in by Sutinen and colleagues from the same research group, in an oral presentation at this years workshop.
Paddy Mallon and colleagues from University of New South Wales always produce important studies at the Workshop. This year was no exception, with a study looking at changes in body composition in patients with elevated cholesterol who were treated with 40mg/day of pravastatin. Although pravastatin is often used in HIV-positive patients to reduce cholesterol, and is preferred over other statins due to fewer drug interactions with ARVs, this was the first study to look at whether it has an impact on body composition.
Although it is now well established that switching from a thymidine analogue to either abacavir or tenofovir can slowly reverse limb fat loss improvements in facial lipoatrophy have not been clearly established.
Michael Dubé from Indiana University reported results from a 48 week study looking at whether extended release niacin (ERN), also known as nicotinic acid or vitamin B3, would be safe and effective in dyslipidaemic HIV-positive patients on HAART.
One of the posters presented at the workshop provided details of implants used to correct buttock lipoatrophy in seven women treated at University of Barcelona. The surgeon, Dr Fontdevila has treated HIV-related lipoatrophy for over four years, predominantly using autologous fat transfer to correct facial lipoatrophy, with approximately 60% of procedures carried out in the plastic surgery department in HIV-positive individuals.
This issue of HTB includes reports from this biannual meeting that this year attracted close to 5000 registered delegates. As with many conferences now, many sessions can be viewed on the internet and provide an excellent opportunity for people who unable to attend the meeting.
Mark Nelson and Laura Waters, for HIVandHepatitis.com
Although the advent of HAART has resulted in a considerable reduction in mortality and morbidity associated with HIV infection, advances in the management of hepatitis B and C both in mono- and co-infected patients continues to somewhat lag behind. This is particularly true for those coinfected with HIV and HBV or HCV, despite the high incidence of coinfection worldwide.
Issues concerning HIV drug resistance are a growing concern in the treatment and management of HIV infection. In the review that follows, Dr. Ian Frank summarizes selected studies on resistance presented at the 3rd IAS meeting in Rio de Janeiro, Brazil.
September 15, 2005 - GlaxoSmithKline (GSK) is informing you that we are making changes to the development program for the investigational CCR5 entry inhibitor, aplaviroc (GW873140), due to safety data observed in Phase IIb studies. GSK has received reports of severe hepatotoxicity with elevated liver enzymes (AST, ALT) and total bilirubin in clinical trials involving treatment-naïve patients. GSK has taken immediate steps to protect the welfare of patients in clinical studies of aplaviroc.
On 17 September 2005, AZT, the first approved antiretroviral drug, manufactured and marketed by GSK, came off patent. On 19 September, the FDA approved several generic formulations of AZT for the US market.
In the 13 August edition of the Lancet, Ginger Lehrman of University of Texas South Western Medical Centre, USA, reported a small study investigating the effects of the drug, valproic acid (an anticonvulsant) on depletion HIV-1 reservoirs. This proof of concept study was conduced in four patients who had been treated with fully virally suppressive HAART (<50 copies/mL) for at least two years and who then were initiated on an intensified HAART regimen which included their original regimens with the addition of 90mg T-20 (enfuvirtide) twice-daily. Following a further 4-6 weeks of stable T-20, patients were initiated on three months of 500-700mg twice-daily oral valproic acid.
This issue of HTB includes reports from this biannual meeting that this year attracted close to 5000 registered delegates. As with many conferences now, many sessions can be viewed on the internet and provide an excellent opportunity for people who unable to attend the meeting.
Previous observational data from over 30 published studies, the earliest dating from 1986, have suggested that men who have been circumcised are at a reduced risk from female-to-male sexual HIV transmission, but up until now this has not been supported by evidence from a prospective randomised trial.
James McIntyre from the Perinatal HIV Research Unit, Johannesburg, presented further analyses from the Treatment Options Preservation Study (TOPS). This is a randomised three-arm trial in which either 4 or 7 days of Combivir were added to the single dose nevirapine received by pregnant women (and the infants received single dose nevirapine or single dose nevirapine plus 4 or 7 days AZT/3TC syrups). We have reported earlier results of this important study in previous issues of HTB.
In the industrialised world, most HAART regimens used in pregnancy include a protease inhibitor (PI). In the UK we have greater experience with nevirapine containing regimens, but practice is changing since the Boehringer Ingelheim hepatoxicity warning for women with >250 CD4 cells/mm3. Some data exist on nelfinavir and several other PIs, but there are little or none to guide use of the newer drugs in pregnancy.
This study is tiny so it is difficult to comment on efficacy. More data on this drug in infants is urgently needed though as some guidelines (South Africa’s for example) are recommending LPV/r for infant first line therapy out of concern that their mothers may have been exposed to single dose nevirapine in MTCT programmes. The PK suggests this needs further investigation.
Dr Humlet acknowledged that the study has limitations. So far, there are no virological outcomes for the children, the systems of reporting are not standardised, and side effects are probably underreported. He added that only 6% of the patients in the MSF cohort currently receiving HAART are children. Furthermore, that obstacles are lack of paediatric fixed dose combinations and confidence of healthcare workers to treat children.
HIV-infected children from the MU-JHU and the Paediatric Infectious Disease Clinic, Mulago were screened for antiretroviral therapy. One hundred and sixty four were screened and 90 were enrolled and 81 received quartered or halved Triomune according to the child’s weight band. The investigators found quartered tablets problematic and flaking so very small children were changed to syrups.
In an oral presentation from the ANRS 1244/1278 study Dr Philippe Msellati of the Institute de Recherché pour le Development, Montpelier, France reported predictors of survival in children enrolled in the study at three years. This observational cohort enrolled children between October 2000 and December 2003 and followed them until the end of September 2004.
The virological benefit from maintaining M184V potentially suggests use of 3TC as an additional active drug in salvage therapy, and has provided evidence (through a different trial design) that the Colate study (which was closed after three years by the DSMB due to poor enrolment) was never able to achieve.
Julio Montaner from Vancouver reported on plasma levels and injection site reactions (ISRs) using the needle-free Biojector delivery system which administers T20, by pressurised gas forcing the drug through the surface of the skin. [1] The results of a bioequivalence study were reported at the beginning of 2005 and the application to market Biojector for use with T20 is already filed with the FDA, although the system is not yet available outside of trials or compassionate access, both of which are largely in the US.
On of the most clinically relevant oral presentations was an overview of approaches to salvage therapy focusing on 'When to switch' and 'How to wait' that was given by Steven Deeks, from University of California. The session started by highlighting the lack of detail provided by current treatment guidelines for management of highly treatment experienced patients.
Foscarnet, a pyrophosphate analogue, continues to make a minor comeback for the treatment of HIV in late stage disease (CD4 <100 cells/mm3, HIV RNA >50,000 copies/mL, 3-class drug failure). Christine Katlama presented data on a group of salvage patients in whom she used an induction regimen of 5g iv bid for 6 weeks followed by a maintenance phase, if they achieved a >1log drop in viral load, of 5g iv bid for two days a week.
Almost every presentation showed extremely good response rates (which showed that we have the tools) and that mental health and substance abuse issues along with general adherence and poor medical care are high on the reasons for poor outcomes. We have a drug pipeline which is still exciting, but that we providers and the health care industry are fighting against cost and political problems that produce restrictions on how best we can deliver this effective treatment.
This report focuses mainly on antiviral activity of compounds that are in development with a few reports on strategy for using existing drugs in difficult situation. A summary of pharmacokinetic and drug interaction studies presented on pipeline drugs are covered in a subsequent article.
Set in the capital city of Rio de Janeiro, the 3rd Conference on AIDS Pathogenesis and Treatment yielded little in the way of groundbreaking research; in addition, there were no oral sessions dedicated to HIV Pharmacology. Only two oral presentations presented pharmacological data. One by Vernazza and colleagues reported the results of the ATARITMO-Study aimed at investigating the pharmacokinetics (PK) and CSF and genital tract penetration in patients on ATV/r boosted monotherapy.
Atazanavir concentrations were decreased by 23-28% when co-administered with RTV and TDF in HIV-positive patients, and decreased by 11-20% in HIV-negative volunteers. In addition, TDF concentrations were increased by 29-37%.
Several posters explored atazanavir (ATV) concentrations when dosed alone and in combination with different doses of RTV. Perhaps the most common thread running through all of these presentations was the large degree of inter-patient variability in ATV concentrations in patients taking the same drug dose.
The interaction between antacids/PPIs/H2 blockers and PIs continues to attract much interest due to the commonplace usage of these agents in HIV positive agents and the previously reported significant interactions between these classes. Investigators from Tibotec evaluated the PK of TMC114/RTV when co-administered with 20 mg of omeprazole od or 150 mg bd of ranitidine in healthy volunteers.
With more HIV-positive women choosing to have children, and using HAART though pregnancy, understanding the PK/PD of different agents in this group of patients is becoming an increasingly important subject area.
Lopinavir/r PK/PD were assessed in children younger than 24 months and showed rapid viral load decay and increase in CD4 cell counts despite the presence the low LPV plasma levels (lower than those described for other age groups).
In an observational cohort study, Moreno and colleagues looked at the incidence of TB in just over 1800 HIV-positive patients who had received HAART at the Hospital Ramón y Cajal. Madrid. Sixty percent of the cohort had acquired through IV drug us and a quarter had a previous AIDS diagnosis. 339 patients (19%) had a positive TB skin test (TST) and TB had been diagnosed in 243 patients (13%) prior to starting HAART.
Monitoring efficacy of TB treatment is essential for individual patient care and public health reasons, but laboratory facilities are often limited in countries with the highest prevalence. ESAT-6 and CFP-10 are immunogenic secreted antigens of M. tuberculosis and may provide an easier surrogate marker for treatment response, although data in HIV/TB coinfected populations is limited.
The 2005 HIV Vaccines and Pathogenesis X7/X8 Keystone Symposia, took place in Banff, Canada. Set deep in the picturesque alpine landscape of the Alberta Rocky mountains at an elevation of approximately 5,000 feet in the grand Banff Fairmont Springs hotel, the latest unveiling of cutting edge research in HIV vaccine developments and pathogenesis took place.
This is the first of a two-part article. Part two will be included in a future issue of HTB and will focus on clinical management including treatment and controversies in HIV/HCV co-infected patients. The above account of the postulated mechanisms by which HCV and HIV cause severe liver damage highlight targets for therapeutic intervention. These include direct inhibition of viral replication, immuno-modulation and anti-fibrotic measures, which will be discussed in the second part of this review article, together with clinical management of HIV/HCV coinfection.
On 12 July a peaceful demonstration, organised by HIV-positive members of the Treatment Action Campaign in South Africa to ensure that people with HIV/AIDS receive antiretroviral treatment at Frontier Hospital and throughout the Eastern Cape, led to the South African Police Services in Queenstown brutally assaulting and then shooting unarmed, peaceful protesters asking for HIV treatment.
In the last issue of HTB we reported that six Indian manufactured generic ARVs received FDA tentative approval. Further approvals have since been granted for a generic combination drug product consisting of lamivudine and zidovudine, manufactured by Aurobindo Pharma (on 7 July 2005); and zidovudine tablets manufactured by Ranbaxy Laboratories (on 13 July).
Is today’s sheer multitude of biological patents (especially on genetics of human beings or human pathogens) killing medical innovation — in addition to generating prohibitive prices for vital medical care?
The Panel on Clinical Practices for Treatment of HIV Infection is providing the readers with the following supplemental recommendations to the April 7, 2005 Guidelines for the Use of Antiretroviral Agents in HIV-1 Infected Adults and Adolescents. Please note that these recommendations are in effect immediately. The text and tables of the full document will be updated at a later date.
This annual Resistance Workshop is primarily a meeting for around 230 specialist researchers to discuss drug resistance. With a few exceptions nearly all the attendees present a poster or oral session, and the research submitted each year is the basis for the programme of the meeting. This meeting is mainly aimed at basic scientists, researchers and clinicians, around one quarter of who are from industry.
The opening session at the meeting was one of only two invited lectures and appropriately for a virology meeting, focused on immunological responses. Entry inhibitors that target human receptors will bring a new awareness of the range of immunological responses in patients. As the newest class of drugs, now in Phase 2/3 studies, this will become an increasing focus for this meeting.
The latest data from TOPS show a significant reduction in nevirapine resistance in the mother if the prolonged maternal exposure following single dose nevirapine is covered by the addition Combivir for 4-7 days. As expected, given the known rate of plasma clearance of nevirapine, the proportion of mothers with resistance, as detected by population based sequencing, was lowest with 7 days cover. This appears to be a sensible strategy to limit the spread of NVP resistance, and to preserve maternal therapy options, in settings where short term HAART for PMTCT is neither available or feasible. Although it is disappointing that neonatal AZT plus 3TC for one week did not effect transmission, this largely reflects the efficacy of single dose nevirapine to reduce transmission during labour and the apparent preservation of treatment options for the infected infants may justify the continuation of this approach.
TOPS compared nevirapine single dose (HIVNET 012 regimen) to single dose nevirapine plus either 4- or 7-days of Combivir, to mother and infant to cover the nevirapine “tail”. In the previous interim analysis of 61 women, resistance was detected in 53.3% receiving nevirapine alone and 9.3% overall in those receiving nevirapine plus Combivir (p=0.001) by standard genotyping at 6 weeks. Enrollment in the single dose nevirapine arm was closed following the interim results.
The investigators reported that using the more sensitive test, 103N or 181C variants were detected in 75% of week 6 samples from women receiving single dose nevirapine prophylaxis (mutant frequency 1-75%, median 7%) and 6/22 (27%) of women receiving single dose nevirapine plus either 4 or 7 days of Combivir (mutant frequency 0.8-8%, median 1.9% and 0.3%-1%, median 0.9%, 4 and 7 days respectively)
Dr Esheleman reported detectable nevirapine resistance in 50/78 (64.1%) of the infants. There were significant differences in the frequency in groups 1-4 (p=0.001). The highest was in group 1 (as HIVNET 012 regimen) in which 20/23 87% infants had nevirapine resistance. The frequency was lower when there was infant but no maternal nevirapine dose, 14/19 (74%) in group 3 or when the infant received AZT in addition to the nevirapine, 12/21 (57%) as in group 2. The lowest frequency of nevirapine resistance was achieved combining the two strategies: no maternal nevirapine and nevirapine plus AZT 4/15 (27%) to the infant, as in group 4.
In a previous comparison of frequency of maternal resistance across subtypes - using samples from the NVAZ and HIVNET012 trials - Susan Eshleman and co-workers revealed that resistance was more frequent in mothers with subtype C (45/65, 69%), than with subtype D (37//97, 36%, p=0.0001) or subtype A (28/144, p=0.0001). [5] This finding was independent of maternal viral load, age, parity or time between dose and resistance testing.
In a cross-sectional analysis of plasma RNA samples collected at 6 weeks, 3 months, 7 months and 12 months; 27/31 (87%), 18/27 (67%), 13/37 (35%), 7/ 54 (13%) respectively had detectable K103N variants. DNA analysis from samples collected at 2 weeks and 12 months found that 23/43 (53%) and 2/48 (4.2%) samples had detectable mutations. Longitudinal analysis of plasma RNA in samples collected 6 weeks to 12 months for 15 women showed similar rates of decay, but mothers with higher levels resistance detected earlier had longer persistence of K103N variants.
The majority of breastfeeding transmission takes place in the first six weeks postpartum. Although single dose nevirapine has been much discussed and studied in terms of maternal and infant resistance patterns, less is known about the effect of single dose nevirapine on breast milk viral load, or about the prevalence of nevirapine-associated mutations in breast milk compared to blood plasma.
At the Resistance Workshop, Nicola Gianotti and colleagues an analysis of viral replicative capacity from this study. Replicative capacity (RC) from the first 31 consecutive patients in the study was measured as p24Ag productivity from recombinant clones after four days in culture. Median replicative capacity ratio was calculated as RC at week 24 divided by RC at study baseline; this was 11.42 (IQR 2.4-57.1) in the treatment interruption group and 1.14 (IQR 1.00-1.28) in the 3TC monotherapy group (p=0.0006).
Previous phenotypic testing had failed to show resistance to tenofovir, because samples had included single 184V mutations, to which TDF is hypersensitive and this cancelled out the increased resistance from 65R and 184V dual mutations.
The low phenotypic change associated with loss of activity with ddI makes predicting response from genotypic results a difficult challenge, for which there is certainly a clinical need. An important suggestion from the audience, similar to other studies, was that cooperation between the researchers in ths study and those involved Jaguar should usefully now cross-validate each set of results.
Using real-time PCR point-mutation tests for M184V, D67N, K70R in reverse transcriptase and L90M in protease, Jeffrey Johnson and colleagues analysed 183 samples from treatment naive patients in the US and Canada, with evidence of transmitted resistance by genotype sequence analysis at diagnosis. Although real-time assays are sensitive to detect strains down to 0.05% of the viral population, a cut-off of 0.5% was used for positive screening in this study.
An analysis from Deenan Pillay on behalf of the UK Collaborative HIV Cohort Study (UK-CHIC) evaluated predictors of survival after diagnosis with multi-drug resistance (MDR). Of 628 patients 54 (9%) died within two years of their MDR diagnosis, defined as at least one primary mutation to nucleosides, NNRTIs and PIs. The cohort was 85% male, median age 43, with a median CD4 at MDR diagnosis of 238 cells/mm3 (IQR 110-376). This rose to 13% at three years. though far fewer patients had this length of follow-up.
A Tentative Approval means that FDA has concluded that a drug product has met all of the agency’s quality, safety and efficacy standards required for marketing in the US, even though it may not yet be marketed in the U.S. due to existing patents and/or exclusivity. It does, however, make the product eligible for use under the President’s Emergency Plan for AIDS Relief (PEPFAR) program outside the United States.
In November 2003, a small group of people living with AIDS, drug users, women and gay men met with the Director General of the World Health Organization Dr. Jong Wook-Lee and the new head of the HIV/AIDS Department, Dr. Jim Kim. This was the first meeting in the history of the epidemic between a Director General and a delegation of PLWHAs from around the world.
On June 28 Médecins Sans Frontières (MSF) published the 8th edition of ‘Untangling the web of price reductions: a pricing guide for the purchase of ARVs in developing countries’. The report shows that while generic production has brought down the prices of most first-line antiretrovirals (ARVs) from over $10,000 in 2000 to as little as $150 per patient in June 2005, prices of newer ARVs and formulations for children are up to 12 times higher.
This interim report highlights progress to date in scaling up HIV treatment and prevention in low- and middle-income countries. The momentum achieved has been the result of a broad range of local, national and international efforts including, first and foremost, those of many of the most highly affected countries. These efforts have been reinforced by financial and technical support from many multilateral and bilateral institutions and donors.
Based on the results from Phase 2 studies, and supported by safety data in a rapidly enrolled group of 300 additional patients, Tibotec announced on 15 June that it plans to submit it’s new protease inhibitor (TMC114) for early approval. This is the first time in ten years (since indinavir) that Phase 2 data have been sufficiently impressive, in a population with currently unmet treatment needs, to justify accelerating approval even more quickly than current Fast Track system. TMC-114 has activity against a broad range of currently PI-resistant virus.
The approval of tipranavir/r is based on 24-week results from of two controlled phase III studies previously reported in HTB (RESIST 1 and 2). A statistically greater percentage of HIV-positive patients taking tipranavir/r achieved treatment response versus the comparator group (40% vs 18%). Treatment response was defined as a confirmed 1 log or greater decrease in HIV RNA from baseline.
The U.S. Food and Drug Administration (FDA) granted Fast Track designation to Schering-Plough’s CCR5 receptor antagonist vicriviroc (SCH-D, SCH-417690). FDA Fast Track programs are designed to facilitate the development and expedite the review of new drugs that are intended to treat serious or life-threatening conditions and that demonstrate the potential to address unmet medical needs.
On August 1 Pfizer announced that it has discontinued clinical development of capravirine, an NNRTI with activity against NNRTI-resistant HIV, that was in phase 2 development. This came as no surprise given the complicated drug interactions that make it difficult to use with other PIs or NNRTIs.
In a letter in the 10th June issue of AIDS, Deborah Cohan and co-workers describe a case in which an infant was infected with multi-drug resistant HIV, despite undetectable plasma HIV-1 RNA levels in the mother. [1] The authors note that the mother was receiving a regimen in which the drug to which the patient was fully sensitive, T-20, may have limited distribution to the genital tract.
Three studies from Johnson et al, Flys et al and Eshleman et al, looking at nevirapine resistance and persistence which we covered in our HTB CROI report are published in the Journal of Infectious Diseases. These are accompanied by an editorial commentary from Scott Hammer entitled (and in danger of becoming the new nevirapine resistance catch phrase): “The more you look the more you find”, in which he provides an overview of the more recent data and its implications.
HIV-positive women have a higher prevalence of HPV infection of the cervix and anus as well as high- and low-grade squamous intraepithelial lesions (HSIL and LSIL) at these sites compared to HIV-negative women, matched for age & risk factors. Similarly HIV-positive men who have sex with other men (MSM) have a higher prevalence of anal HPV infection and anal SIL and carcinoma than HIV negative MSMs. During the last decade it has been shown conclusively that HPV infection is implicated in more than 99% of cases of invasive cervical carcinoma.
Data presented at the 2005 National HIV Prevention Conference in Atlanta, Georgia, indicate that roughly one million Americans were living with HIV at the end of 2003 and that HIV prevalence remains extremely high among African-American men who have sex with men (MSM) in several U.S. cities. Other data show that while HIV diagnoses reported among adolescent and young adult females have declined steadily, diagnoses in males have increased in recent years. Data presented also show that some prevention programs are substantially reducing sexual risk behavior among people with HIV and those at risk for infection, and that voluntary rapid testing efforts are increasing the number of people who find out their HIV status.
To characterize the re-emergence of infectious syphilis in the United Kingdom between 1997 and 2003, the authors conducted a retrospective analysis of surveillance data from genitourinary medicine clinics and additional data collected through enhanced surveillance.
The median gestation in the Royal Free study was 37 weeks for women using Kaletra; and 8 women had emergency rather than elective C-sections. Perhaps they could have been allowed to have a spontaneous vaginal delivery given the data from the Chelsea & Westminster. Additionally, there are still insufficient data to inform mothers of the benefits of pre-labour C-section when HIV plasma contains less than 50 HIV RNA copies/mL.
For clinics that do not already use TDM routinely, PENTA 14, a randomised trial of differing levels of TDM compared with no TDM in children starting or switching to a new antiretroviral regimen is currently recruiting in the UK. Please visit the trials section of the PENTA website for more details.
Several presentations previous meetings have documented a significant number of sexual transmission of HCV to HIV-positive gay men. In an oral presentation at this years meeting, Danta and colleagues from HIV and Acute HCV group characterised HCV transmission in 90 gay men seen at the Royal Free Hospital, Chelsea and Westminster Hospital or Brighton Hospital. Transmission factors were accessed by questionnaire, and compared in a case control study to mono-infected patients, matched by age, duration of infection and duration of HAART.
A case report from Liverpool University, detailed the response of a 40 year old Zambian women, diagnosed in June 2004 with a CD4 count of 34 cells/mm3, who was started on AZT/3TC/efavirenz. Five-drug rifampicin-based treatment for pulmonary TB was started 2 months later, and the dose of efavirenz was increased to 800mg daily.
An interesting case study presented as a poster at the meeting, detailed how a 36 year old man from South Africa who started HAART in November 2002, was forced to start and stop treatment five times. A short time after treatment was started, vomiting, diarrhoea and stomach cramps occurred to a sufficiently severe and unmanageable extent that treatment was stopped. Repeating this sequence a further four times strengthened the association between HIV-treatment and symptoms.
All clinicians who deal with HIV positive gay men’s sexual health should be vigilant to the possible presenting symptoms of LGV and wherever possible enrol the assistance of the HPA in establishing a diagnosis. Adequate treatment should be initiated as soon as possible thereby avoiding the potentially serious sequelae of untreated LGV....
This joint meeting – the British HIV Association (BHIVA) jointly orgnanised the meeting with British Association for Sexual Health and HIV (BASHH) - drew over 800 delegates to hear a wide range of excellent presentations, was held just as this issue of HTB went to press.
CONFERENCE REPORTS: Third European HIV Drug Resistance Workshop, 30 March – 1 April, 2005, Athens
Despite a grand and growing panoply of antiretrovirals, how little we know about HIV can be humbling. For example, noted Hans-Georg Kraeusslich (University Clinic, Heidelberg), several schematic slides at the Third European HIV Drug Resistance Workshop portrayed HIV as a crisply uniform icosahedron-a 20-sided globe [1]. His own immaculate slides of ice-coated virions showed snowball-smooth spheres of discrepant size.
So at this point Boehringer predicts that most people with more than seven mutations from the set of 21 will respond poorly to tipranavir. But company virologists have not entirely tossed out the four-mutation set of changes at positions 33, 82, 84, and 90, arguing that they denote a highly resistant virus that tipranavir will struggle to control. But many may find it odd to juggle two scores – one that includes L90M and one that does not.
CCR5 antagonists - with Pfizer’s maraviroc leading the development race - will be the next new antiretroviral class. These drugs bollix HIV docking to CCR5, one of two key coreceptors the virus can use to breach CD4 cells after grabbing hold of CD4 itself.
CONFERENCE REPORTS: Paediatric reports from 12th Conference on Retrovirus and Opportunistic Infections, 22-25 February 2005, Boston
A once-daily dosing schedule for HIV-positive children may offer an advantage to families and healthcare workers in terms of convenience and adherence. The currently approved paediatric dose of lopinavir/ritonavir (LPV/r, Kaletra) is 230/57.5 mg/m2 taken twice daily with food. Gwenda Verweel and colleagues evaluated the pharmacokinetics, tolerability, and efficacy of once-daily dosing of LPV/r in children.
Lopinavir/ritonavir is increasingly recommended for treating young infants but in the absence of published data. Ellen Chadwick and colleagues from the PACTG 1030 study group evaluated dose requirements for babies <6 months that provide systemic exposure similar to that which has been shown to be safe and effective in older children and adults.
Alessandra Viganò and colleagues reported findings from a study to assess the strategy of replacing protease inhibitor (PI) by efavirenz (EFV) and stavudine (d4T) by tenofovir (TDF) in HIV-positive children with long-lasting viral suppression.
CONFERENCE REPORTS: 40th Annual Meeting of the European Association for the Study of the Liver, 13-17 April, 2005, Paris
Roche Laboratories issued a “Dear Health Care Provider” letter to ID/GUM and HIV physicians, nurses and pharmacists to communicate an important drug interaction warning for saquinavir/ritonavir, used as part of combination therapy for treatment of HIV infection.
Following discussion with the European Medicines Agencies scientific committee, the Committee for Medicinal Products for Human Use (CHMP), Bristol-Myers Squibb and Gilead Sciences International Limited are writing to inform you of new European recommendations regarding the co-administration of didanosine and tenofovir DF.
CONFERENCE REPORTS
12th Conference on Retrovirus and Opportunistic Infections,
22-25 February, Boston, 2005
At present the co-administration of other antiretroviral therapy to cover part or all of the period of actual nevirapine exposure seems the most likely approach, but data from the Mashi study suggest that early nevirapine administration to the neonate may have equal efficacy to maternal dose. If validated this would clearly avoid the risk of nevirapine resistance developing in the mother.
In the Coutsoudis et al meta-analysis of over 4,000 breastfeeding mother-infant pairs the estimated rate of late postnatal transmission in infants who were not receiving any ARV prophylaxis was 4.2% at age 6 months and with their estimate of 0.89% per month of breastfeeding, for 6 months of breastfeeding, would be about 5% at age 7 months. So not much different than with no infant prophylaxis at all.
A poster authored by Louise Kuhn and colleagues evaluated the effect of maternal HIV status on a group of uninfected infants born to HIV positive mothers in Lusaka, Zambia. Due to MTCT programmes this group is increasing and although they are not infected themselves, mortality and morbidity among exposed, uninfected children is substantial in sub Saharan Africa.
Resistance in infected infants exposed to maternal or infant MTCT strategies. Two studies looked at resistance in infected infants exposed to maternal or infant MTCT strategies.
A prospective, longitudinal, 48 month study by Italian researchers concludes that in HIV infected children, a 12 month treatment with tenofovir (TDF) was not associated with an impairment on bone mineral accrual.
Daniel Douek of The Vaccine Research Centre, NIAID, NIH, Bethesda, MD, USA proposed a model of HIV pathogenesis in which the loss of CD4 T cells is a result of an early massive infection and deletion of memory CD4 T cells, followed by exhaustion of the CD4 T cell pool as a result of chronic immune activation.
One individual case study, partly presented before the conference, generated a lot of activity at the meeting for several reasons. Part of the controversy related to this case having been presented in a New York City Department of Health press conference two weeks prior to this strictly embargoed meeting, dominating media attention. It was then admitted as a late poster [1] and allotted an additional four-speaker oral symposium that was added to the programme for Thursday evening and which has been added to the webcast presentations.
The most likely explanation for these results would appear to be failure of the assays used to test for HIV antibodies. However the possibility must be considered that sero-reversion has taken place. It would be highly recommendable that these results should be validated by other labs. The main problem here is that there is no clinical indication to re-test HIV positive patients for p24 antibodies following diagnosis, so we have no idea if there is an actual phenomena here that has until now been missed. Whatever the case, sero-reversion should not be taken to be equivocal with viral eradication.
An interim 24-week analysis of data from 497 patients in a multinational study of the new protease inhibitor TMC114 with ritonavir, demonstrated exciting efficacy in three-class-experienced patients with limited treatment options and was presented as an oral late-breaker session.
PA-457 is the first of a new class of drugs called maturation inhibitors, which block the conversion of the HIV-1 capsid precursor CA-SP1 (p25) to mature capsid protein (p24) resulting in the release of non-infectious virus particles. It has been shown to potently inhibit the HIV-1 replication, including strains resistant to currently prescribed drugs and is highly active in the SCID mouse model.
When Richard Haubrich presented the exciting data on the use of TMC114, the new protease inhibitor from Tibotec, as a late breaker on Friday, I realised that a mere 12 years has passed since I had sat in the World Aids Conference in Berlin in 1993 with the distinct feeling that nothing was going to halt the onslaught of disease that was then engulfing my patients. Now my thoughts are like those of Dame Maggie Smith in ‘The Prime of Miss Jean Brodie’ who proclaims “give me a girl and she’s mine for life”. The vast majority of those with HIV can look forward to a long and relatively healthy life with an improving selection of agents, not necessarily needed to improve virologic control but altered to ameliorate toxicity and tolerability concerns.
The D:A:D study is the largest and longest running prospective cohort study assessing the relationship between HAART and cardiovascular disease. This is a multinational study including over 23,000 patients enrolled in national cohorts from Europe, Australia and the US. Data presented in an oral presentation from the latest analysis of this important dataset, which now includes over 76,000 patient years with median exposure to HAART of 4.5 years, continued to show that NNRTI- or PI-including combination therapy is an independent risk factor for cardiovascular disease.
In an oral presentation at the conference, a double blind, randomised trial carried out by French researchers with 122 subjects over 16 weeks showed the efficacy of using Omega-3 polyunsaturated fatty acids to treat hypertriglyceridaemia in patients receiving HAART. Sixty HIV-positive patients received Maxepa capsules containing 1g fish oil (2 capsules, 3 times a day, 18% EPA, 12% DHA) and 62-patients received placebo (1g paraffine oil capsules), all of whom were receiving HAART and had high triglycerides greater than 2 g/L after four weeks of appropriate dietary advice. Patients were given 8 weeks of treatment or placebo, followed by 8 weeks of open label treatment.
One of the most publicised UK studies at the conference included an oral presentation of the RAVE Study. This is a switch study comparing differences in fat recovery and lipid parameter when using tenofovir or abacavir in patients with lipoatrophy who are changing from AZT or d4T. Results presented by Graeme Moyle from the Chelsea and Westminster Hospital showed that tenofovir was associated with fewer treatment discontinuations and greater improvements in lipid parameters.
Previous articles in HTB have tracked the rationale for potential benefit of rosiglitazone (RSG), a PPARg agonist and transcription regulator, to reverse lipoatrophy, together with reports from several studies that found conflicting clinical results, but generally found no benefit. HIV-positive patients with lipoatrophy have decreased PPAR-g and rosiglitazone has increased limb fat in HIV-negative adults with Type-2 Diabetes Mellitis (who also have reduces PPAR-g). A report from last years Lipodystrophy Workshop highlighted a study from Patrick Mallon showing that thymidine analogues could work downstream of any beneficial effect, negating any potential benefit.
An international, phase II study of the anti-hepatitis B drug Entecavir (ETV) showed that in HIV-HBV coinfected patients with 3TC-resistant HBV, adding ETV therapy reduced HBV DNA and normalised ALT within 24 weeks, with tolerability comparable to placebo. No interaction with HIV infection or HAART was reported. ETV-038 is an ongoing, double blind, comparative trial with 68 coinfected participants who had HBV viraemia while being treated with 3TC. The study included sites in Brazil, UK, USA, Argentina and Spain. Most (88%) had HBV with at least one 3TC-resistant mutation. Patients were randomised to receive ETV 1mg (n=51) or placebo (n=17) once-daily for 24 weeks followed by open label ETV for all participants for another 24 weeks. All patients continued taking 3TC.
Marion Peters and colleagues presented 48-week results from a randomised, double blind, placebo controlled trial study comparing tenofovir disoproxil fumarate (TDF) to adefovir dipivoxil (ADV) in coinfected patients. The non-inferiority design indeed showed that TDF was not inferior to ADV for the treatment of hepatitis B virus (HBV). ADV 10mg is active against both wild type and lamivudine-resistant HBV and is licensed to treat HBV. TDF 300mg is licensed to treat HIV and has in vitro activity against both wild type and lamivudine-resistant HBV but this has not been studied in randomised, controlled trials. The aim of ACTG A5127 was to assess TDF 300mg daily compared to ADV 10mg daily using time weighted average change from baseline in serum HBV DNA up to week 48.
People living with AIDS in developing countries that currently use d4T manufactured by BMS, may face a shortage. This was recently communicated to MSF by BMS, and was confirmed in the Wall Street Journal last week (“Demand for Two AIDS Treatments Could Soon Exceed Supply”, e-drug March 9th). In the article Paul Lalvani, procurement manager for the Global Fund in Geneva, said that some developing countries “have not been able to access the product”.
India will start granting product patents for medicines - something they have not done since 1970 - without the necessary procedures in place to safeguard against increases in medicine prices. India amended its 1970 Patent Act in order to be compliant with the requirements of the World Trade Organization (WTO).
US-based Pfizer has emerged as the biggest pharma patent applicant in India as the Kolkata-based Patents Office opened the mailbox of patent pleas for pharma and agrochem inventions for 1995-2005. Mailbox applications are meant to recognise inventions as India switches to a product patent regime.
London-based GlaxoSmithKline (GSK) has called on the UK to use its presidency of the Group of Eight (G8) most industrialised countries to ensure that emerging economic powers such as China, India and Brazil respect patents and take action against counterfeiting.
On March 17, 2005, separate US House and Senate bills designated India as the 16th country to receive President Bush’s Emergency Plan for HIV/AIDS Relief (PEPFAR) funds.
Roche announced on 22 February 2005, that the European regulatory agency (CHMP, Committee for Medicinal Products for Human Use) delivered a positive opinion to market 500 mg saquinavir HGC (Invirase). This new formulation will reduce dosing for most patients to two pills twice daily.
As part of its regular review of products in its pharmaceutical portfolio, Roche has initiated discussions with worldwide regulatory authorities on plans to discontinue two of its HIV drugs, ddC (zalcitabine, Hivid) and saquinavir, soft capsule formulation (Fortovase), in the near future.
People in the US using the entry inhibitor T-20 (enfuvirtide) have started to use a needle-free injection method of delivery for this drug. The system, called Biojector 2000, uses compressed carbon dioxide to force the drug at pressure through the skin from a pre-mixed syringe.
In February, PegInterferon (Pegysys, Roche) was approved for treatment for hepatitis C in clincally stable patients that are coinfected with HIV. The European and US decision came within a few weeks of each other.
On 25 February, the EU Commission approved Pegasys (peginterferon alfa-2a (40KD)) for the treatment of HBeAg-positive and HBeAg-negative chronic hepatitis B.
The Treatment Alert that forms the first article of this issue of HTB concerns the interactions between atazanavir and omeprazole, but relates to a contraindication against prescribing proton-pump inhibitors or H2-receptor blockers or any acidreducing agents with some protease inhibitors (atazanavir, fosamprenavir, indinavir).
Important new pharmacokinetic data demonstrating that atazanavir sulfate (Reyataz) combined with ritonavir (Norvir) and proton pump inhibitors should not be coadministered
CONFERENCE REPORT:
7th International Congress on Drug Therapy in HIV Infection (ICDTHI), 14-18 November 2004, Glasgow.
Three randomised placebo-controlled studies presented in Glasgow demonstrated the usefulness of nandrolone decanoate (ND) in combating weight loss of HIV-positive men. One found that ND increased body weight in subjects when compared to placebo or testosterone; a second trial found that two higher doses of ND were more effective than a lower dose or placebo; and a third trial concluded that ND was better than placebo but little different from recombinant human growth hormone (rhGH) in its ability to increase lean body mass in the subjects.
Two British studies of the co-administration of atazanavir (ATZ), saquinavir (SQV) and ritonavir (RTV) found that ATZ increased plasma and intracellular (IC) exposure and Cmin of SQV but not RTV, and that the IC concentrations were higher than the plasma concentrations for all the PIs. The researchers conclude that the addition of ATV to a daily SQV/RTV regimen may be useful for people whose SQV concentrations are below the effective level.
A retrospective analysis of requests for atazanavir (ATZ) therapeutic drug monitoring (TDM) was carried out by Sara Gibbons and colleagues at the University of Liverpool, who concluded that there was a marked variability in plasma ATZ concentrations in the clinical setting. The authors of this poster write that this was due to both a variety of dosing regimens and variability between patients on the same regimen. Their findings emphasise the usefulness of TD with this drug.
In a second study, Paul Holmes and colleagues at the Chelsea and Westminster Hospital, London, presented results from clinical use of atazanavir in 241 patients since June 2004. Of note, 231 patients used boosted atazanavir and only 10/241 used unboosted atazanavir (ATZ).
A poster by Christopher S Alexander and colleagues from the British Columbia Centre for excellence in HIV/AIDS, Vancouver, Canada, looked at the interaction between atazanavir/ritonavir (ATZ/rtv) and nevirapine (NVP) and/or tenofovir (TDF) as observed in a clinical setting. The results suggest that RTV boosting of ATV reduces the interaction with TDF but it may not do the same with NVP.
It is encouraging to see that side effects in this study were not particularly frequent nor severe. This cohort is followed fairly intensively, especially on initiation of therapy, so hopefully any side effects are detected early. When analysed with a CD4 cut-off of 250 cells/mm3, as used in other studies and in the Dear Dr letter from Boehringer, the authors saw no difference in rates of toxicity. The authors therefore postulated that the haemodilution of pregnancy might mean that the higher rate of side-effects seen in non-pregnant women with CD4 >250 cells/mm3 might not apply to pregnant women, and a lower cut-off of 200 cells/mm3 might be more appropriate.
In a poster presentation from St Mary’s Family Clinic, Anet Alexanian reported better virological and immunological outcomes in children receiving higher doses of nevirapine than those recommended by the manufacturer. The study was a case note review of children on nevirapine from whom blood samples had been sent for therapeutic drug monitoring to the Liverpool TDM service.
The study observed that observed dosing meant that adherence could not explain these levels, but that poor ritonavir storage could. A previous quality control analysis of drugs sourced in Africa found both SQV formulations contained drug content to USP standards but the ritonavir levels were 16-19% lower than stated in the label.
Importantly, a higher proportion of coinfected patients than HIV-negative patients successfully completed their course of TB treatment (110/115 vs 99/114).
The main decline was among those people who stopped treatment because of toxicities and patient/doctor choice. Patients with HCV had a higher incidence of stopping treatment for these reasons than those without HCV. The authors write that managing adverse events must remain “a key intervention” in maintaining HAART in patients with hepatitis C coinfection.
The potential to use reduced doses of d4T in patients who delevop early symptoms of either peripheral neuropathy of lipoatrophy is a particularly important first management choice for patients using WHO-recommmended fixed dose combination (FDCs) regimens. Similar findings have been frequently reported in HTB.
An unprecedented meeting took place in Mumbai, India in January between four manufacturers of affordable generic antiretroviral medicines and advocates for HIV treatment access drawn from every region of the world.
Medicines supplied by Indian drug majors had been a lifeline not just for HIV/AIDS patients in the country, but more so in African countries like Nigeria. “The fact that we have access to treatment simply means that more of us can stay alive,” says Ms Rolake Nwagwu of Nigeria’s Positive Treatment Action Movement.
Ranbaxy Laboratories Limited (Ranbaxy) announced on 10 January that the Company has so far made three filings of its Anti-Retrovirals (ARVs), to the USFDA for its approval under the expedited review process of the US Presidents Emergency Plan for AIDS Relief (PEPFAR).
The Food and Drug Administration (FDA) announced on 25 January the tentative approval of a copackaged antiretroviral drug regimen, consisting of fixed dose combination of AZT/3TC/nevirapine tablets for the treatment of HIV-1 infection in adults. It is manufactured by Aspen Pharmacare of South Africa.
The Minister of Health has been ordered by the Pretoria High Court to pay punitive costs in a case brought earlier this year by the TAC. She must pay the TAC’s costs on the scale as between attorney and client, as well as the cost of one counsel. This is an unprecedented judgement. The judgment is important because punitive costs are seldom granted; such awards indicate that the court is displeased by the conduct of a party – here the Minister. The Minister has therefore wasted money in defending an indefensible case. She must account for her conduct.
The TAC has requested MSD, the distributer of efavirenz, an essential antiretroviral medicine, to grant voluntary licenses to generic manufacturers on similar terms to those reached with GSK or Boehringer Ingelheim. Should MSD fail to do so, we will consider litigation for compulsory licenses.
New guidelines for use of PEP for prevention of HIV transmission in the US were published in the January 21 issue of CDC’s Morbidity and Mortality Weekly Report.
A new 500 mg tablet formulation of the HIV protease inhibitor, Invirase (saquinavir mesylate) was approved by the FDA in the US, on December 17, 2004, a. The dosage and administration for Invirase in adults (over the age of 16 years) is 1000 mg twice a day (taken as either two 500 mg tablets or five 200 mg capsules) in combination with ritonavir 100 mg twice a day. The new tablet formulation reduces the pill burden compared to the capsule formulation.
A study published in the 3 January issue of AIDS evaluated the potential effects on antiretroviral metabolism of two herbal medicines commonly used in South African traditional medicine and identified the potential for clinically significant drug interactions for both H. hemerocallidea and Sutherlandia.
The Clinical Pharmacology section of the Crixivan (indinavir) label has been revised to include pharmacokinetic data from a study (PACTG 358) in HIV-infected pregnant women. Results from this study show substantially reduced indinavir concentrations in women at weeks 30-32 weeks gestation compared to postpartum. Based on these data, the Precautions Sections now states that indinavir is not recommended in HIV-infected pregnant patients.
The Medical Foundation for AIDS & Sexual Health (MedFASH) has launched a new publication aimed at providing practical advice for the primary healthcare team on HIV.
InterCare, a charity based in Leicester, has been providing unused dispensed medicines that would otherwise be destroyed to clinics in countries with limited access to medications mainly in Africa, for over 20 years.
The AmpliChip CYP450 Test is powered by Affymetrix technology. It provides comprehensive coverage of gene variations – including deletions and duplications – for the 2D6 and 2C19 genes, which play a role in the metabolism of about 25% of all prescription drugs.
FDA is announcing the availability of a draft guidance for industry entitled “Role of HIV Drug Resistance Testing in Antiretroviral Drug Development.” This draft guidance addresses the role of HIV resistance testing during antiretroviral drug development and postmarketing.
The last issue of HTB for 2004 and first issue of 2005 includes conference reports form the Lipodystrophy Workshop and ICAAC and refers to the Boston Hepatitis meeting and the bi-annual Glasgow Congress held in November. Full coverage of the Glasgow meeting will be included in the next issue of HTB.
Important new clinical data: potential early virologic failure associated with the combination antiretroviral regimen of tenofovir, ddI, and either efavirenz or nevirapine;
CONFERENCE REPORT:
6th International Workshop on Adverse Drug Reactions & Lipodystrophy in HIV
This annual workshop, largely focused on lipodystrophy and metabolic complications, provides an opportunity to assess research developments over the previous year. It also addresses the implications on clinical practice, and to a more limited extent, the implications for clinical management. From a community perspective, this research is painfully slow, often based on in vitro cell studies and mouse and rat models.
The most significant research into lipoatrophy over the last few years have come from several Australian research groups. The plausibility for the link between mitochondrial toxicity and lipoatrophy is convincingly strengthened by research that correlates peripheral and facial fat loss with reduced mitochondria cell number in adipocytes).
Even earlier changes in gene-expression implicated in lipoatrophy were presented by Paddy Mallon and colleagues from St Vincent’s Hospital, Sydney, who described changes in mitochondrial and nuclear gene expression in adipose tissue in 20 HIVnegative volunteers, randomised to standard dose dual nucleoside therapy (AZT/3TC or d4T/3TC) for 6 weeks.
Uridine had no effect by itself, but on ddC and d4T-exposed cells, normalised lipid morphology and rate of apoptosis. Pharmacokinetic data was provided from a study in eight HIV-negative volunteers (4 men, 4 women) following single dose NucleomaxX (36g, dissolved in orange juice).
A retrospective questionnaire/interview study of 63 patients taking lopinavir/ritonavir (LPV/r, Kaletra) at the Chelsea and Westminster Hospital in London found that only 43% were taking the drug with adequate food and just over a quarter of patients were taking Kaletra on an empty stomach.
At this years Lipodystrophy meeting she reported results from a pilot study of growth hormone dosed at 0.028mg/Kg daily for 24 weeks in eight adolescents with visceral fat accumulation (defined as intra-abdominal tissue (IAT) content >41cm2 by MRI scan at L4). This is less than the therapeutic rHGH dose for children with growth impairment. Abnormal glucose tolerance, diabetes or ongoing malignancies were exclusion criteria for the study.
Weight loss in the HAART era may be driven by residual HIV infection in cells of the monocyte/macrophage lineage, conclude Shikuma and colleagues from the University of Hawaii after a study involving 67 HIV-positive people, a subset of the Hawaii Aging with HIV longitudinal cohort study.
Coronary artery bypass graft (CABG) is a feasible and safe procedure in HIV-positive patients, conclude Boccara and colleagues at the French Italian Study on Coronary artery disease in AIDS patients (FRISCA-2). There was no difference in immediate postoperative outcomes between HIV-positive and HIV-negative patients. However. long-term follow-up showed higher rates of major adverse cardiac events (MACE) was significantly higher in HIV-positive patients due to an increased rate of repeat revascularisation procedure (reCABG and percutaneous coronary intervention [PCI]).
A Spanish study of 61 HIV-positive men on ARV therapy found endothelial dysfunction (ED) in 18%, a similar proportion to naive patients. Its presence was independent of fat redistribution abnormalities, plasma adipokines, lipoproteins, immune status or use of PIs or NNRTIs. Low adiponectin (AD) plasma levels are observed in patients on treatment with fat redistribution abnormalities (FRA) and low levels of adiponectin have been associated with impaired vasoreactivity in the general population. Previous studies found a significant relationship between use of PIs and endothelial dysfunction.
Pravastatin improves the dyslipidaemia of HIV-positive people on ART but this does not translate to improved endothelial function (EF). Persistently elevated C-reactive protein (CRP) values suggest that there may be an ongoing stimulus towards cardiovascular (CV) risk that has yet to be elucidated, Sklar and colleagues in the United States conclude from a randomised, placebo-controlled, crossover study.
Treatment for 4 weeks with indinavir (IDV, Crixivan) monotherapy markedly impairs endothelial function and insulin-mediated vasodilation, without significant impairment of whole-body glucose disposal, according to an American study. So it appears unlikely that insulin resistance plays a major role in the induction of endothelial dysfunction.
The researchers concluded that 3 cycles of IL-2 did not have significant metabolic effects on patients receiving stable ARV therapy. However, structured TI is associated with immediate and sustained decreases in cholesterol levels (both LDL and HDL) and triglycerides (TG). The effects on glucose and insulin metabolism were limited in this cohort.
Switching patients with virologically controlled HIV infection to a simplified maintenance ARV regimen results in an improved lipid profile, according to the preliminary findings of a French randomised, multicentre trial of 143 patients.
A European study of 1052 patients starting ART since 1999 found that those with HIV/HCV coinfection were more likely to discontinue all or part of their ART regimens due to toxicity and patient/physician choice than were HIV-positive patients without HCV. Moorcroft and colleagues in the EuroSIDA study group conclude that managing adverse events must remain a key intervention in maintaining HAART.
Although several posters focused on practical and corrective treatments for lipoatrophy, only a few studies provided new information. The benefit and efficacy of New-fill (Poly-L-Lactic Acid, PLA, Sculptra) has already covered extensively in HTB in reports from previous years meetings. None of the studies at this year’s Workshop provided longer-term efficacy data or additional safety concerns to those already reported from those earlier studies.
One on the most anticipated studies at ICAAC was the 24-week results from tipranavir RESIST-1 study: Randomised Evaluation of Strategic Intervention in Multi-Drug Resistant Patients with Tipranavir, presented by Charles Hicks from Duke University, North Carolina. RESIST-2, the European sister study in slightly more experienced and resistant patients will be presented a month later at Glasgow.
d-d4FC (Reverset) is a cytidine analogue reverse transcriptase inhibitor that has shown in vitro activity to HIV resistant to 3TC, AZT, tenofovir and other RTIs. First in vivo data, from exposure to 10 days monotherapy in treatment naïve patients, achieved mean viral load reductions of –1.77 log after 10 days exposure to 200mg dose, and was presented at the 2004 retrovirus conference.
Download .pdf document of this issue.
This information is designed to support, not replace, the relationship that exists between you and your doctor.