2008
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- EDITORIAL
- Welcome to the July/August issue of HTB and summer reading that includes reports from the International HIV Resistance Worshop held recently in Sitges. We continue with additional reports from the BHIVA spring conference and conclude, finally, our coverage from the Retrovirus conference held back in February.
CONFERENCE REPORTS: XVII International HIV Resistance Workshop (IHDRW), 6-10 June 2008, Sitges
- Introduction
- Despite the fall in the value of the dollar, European delegates are fortunate that this specialist resistance workshop still alternates between European and North American sites. This years meeting in Sitges included a healthy balance between basic science and studies with more direct clinical importance.
- Integrase inhibitor resistance and cross-resistance: weighing viral fitness and the option to benefit from second-generation compounds
- Simon Collins, HIV i-Base
- The data on viral fitness suggests any benefit is likely to be short term, and unlikely to outweigh the risk from accumulating further resistance, especially once Q148 changes have occurred.
- Understanding etravirine susceptibility: new weighted genotype score and phenotypic cut-offs
- Simon Collins, HIV i-Base
- Several clinicians at the meeting, including Jonathan Shapiro found the upper cut-off levels unconvincing as an aid for clinical decisions. In the UK, where phenotype tests are used less frequently, the new genotypic weighed score analysis will be of most relevance.
- Pipeline antiretrovirals: IDX899, CHX157 and beviramat
- Simon Collins, HIV i-Base
- An oral presentation by Rob Murphy [1] summarised two posters at the workshop that presented information on a new NNRTI being developed by Idenix.
- Lack of virological impact of treatment intensification in suppressed patients supports latent viral reservoir as source of residual viraemia
- Simon Collins, HIV i-Base
- This study supports research first presented at the resistance workshop several years ago by Lisa Frenkel, who found that 8/11 children with generally suppressed viraemia had no evolution of viral divergence since starting treatment, implying ongoing viraemia was seeded from latently infected cells rather than a partially activated reservoirs as suggested by others.
- Detecting viral tropism: impact of a more sensitive Trofile (ES) assay
- Simon Collins, HIV i-Base
- One important aspect of the genotype V3 approach is the potential to use this as a screening test for patients who are virally suppressed on their current treatment, but who wish to switch to CCR5 inhibitors due to tolerability issues on their current regimen. While phenotype tests require detectable viral load (>500 copies/mL) the genotype tests can work with plasma RNA and proviral DNA.
- NNRTI resistance in infants prophylaxed with single-dose nevirapine varies by the timing of infection
- Polly Clayden, HIV i-Base
- The investigators noted a low rate of mother-to-child transmission among infants whose mothers received pre-partum AZT in addition to sdNVP. But this was only a minority of women and access needs to be improved.
- Low frequency K103N mutations are associated with poor virological response to NNRTI based therapy
- Polly Clayden, HIV i-Base
- In this study, pre-treatment samples were tested for K103N mutations using an allele-specific real time PCR (AS-PCR). Population sequencing was performed on samples from women who did not achieve a viral load <50 copies/mL or did not sustain viral suppression to 78 weeks.
CONFERENCE REPORTS: 14th Annual BHIVA Conference, 23–25 April 2008, Belfast
- Introduction
- The annual BHIVA spring conference held this year in Dublin, has two main aims. In addition to presenting overview lectures on important aspects of HIV care and management - often given by international experts, it aims to encourage UK-based research and case studies by presenting research from junior doctors and researchers.
- Bone problems raised in several UK studies
- Simon Collins, HIV i-Base
- Low calcium and phosphate levels were more common in patients on HAART and were seen in 47% vs 32% (p=0.06), and 30% vs 5% (p<0.0001) patients, but were not related to tenofovir use. Low vitamin D levels were more common in women than men (8% vs 2%), all of whom were non-Caucasian.
- Late diagnosis in adolescence of vertically acquired HIV infection
- Polly Clayden, HIV i-Base
- Young people with vertically acquired HIV infection are surviving childhood without ART and being diagnosed in adolescence. In this cohort a third were asymptomatic, highlighting the importance of testing all children born to HIV infected women, regardless of age or symptoms.
- Case study of multi-drug resistant woman receiving newer antiretroviral drugs in pregnancy
- Polly Clayden, HIV i-Base
- The infants received ARV prophylaxis with enfuvirtide, nevirapine and ddI. The investigators noted that enfurvirtide was undetectable and darunavir/ritonavir and etravirine were detectable in cord blood. The infants’ adverse events included injection site reactions, hypertriglyceridaemia, anaemia, transient hypereosinophilia and raised alanine transferase.
- Predictors of treatment failure in Western Cape, South Africa
- Polly Clayden, HIV i-Base
- The high prevalence of a very low baseline CD4 is concerning in light of its association with failure. Our study adds insight into the role of treatment interruption, choice of NNRTI and MTCT exposure. Further study of treatment interruption and travel is needed working towards intervention.
- Late pregnancy loss in HIV-positive women
- Polly Clayden, HIV i-Base
- The investigators described the rate of late loss in pregnancy as high (8%) compared to background general population rate of 2% (4% in east London). Although they were unable to confirm cause of this rate of late loss, they highlight the need for sexual health screening during pregnancy, which in this cohort only occurred in 53% of women undergoing review.
- Renal tubular dysfunction with tenofovir-based HAART in four vertically infected adolescents
- Polly Clayden, HIV i-Base
- Although unlicensed, tenofovir is widely used in HAART experienced paediatric cohorts resulting in cases of renal tubular dysfunction. Paediatric formulations and pharmacokinetic studies are currently recruiting with results eagerly awaited.
CONFERENCE REPORTS: 15th Conference on Retroviruses and Opportunistic Infections, Boston, 2-6 February 2008
- Introduction
- The last three issues of HTB included reports on antiretrovirals and treatment strategies, prevention of mother-to-child transmission (PMTCT), paediatrics, hepatitis coinfection, opportunistic infections and treatment access from this important conference.
- The unmet need for contraception services for women receiving ART
- Polly Clayden, HIV i-Base
- The first part of the conclusion from the Abijan study was curious; the effectiveness of the lactational amenorrhea method of contraception has been well documented and is reported to be 98% effective “with perfect use”. Surely any differences in pregnancy incidence between the two feeding groups would be masked by the high rate of uptake of contraception by all the women in this study, which at 78% is to be applauded and is considerably higher than the background rate in Cote d’Ivoire (<10%) and most African countries.
- Valacyclovir decreases plasma and genital viral loads in HSV-2/HIV-1 co-infected women
- Polly Clayden, HIV i-Base
- Results from the HPTN 039 study conducted by the same group were also presented at this conference [2]. This was a randomised, placebo-controlled trial to determine whether HSV-2 suppression with twice-daily acyclovir reduces the risk of HIV acquisition among women in Africa and men who have sex with men (MSM) in the Americas (n=3251).
- HPV genotypes in HIV-positive women in Zimbabwe and Uganda
- Polly Clayden, HIV i-Base
- Both these studies and another from Zambia [3] highlight the question of whether current HPV vaccines will be effective in populations with a significant diversity and multiplicity of HPV types. HPV vaccine development of the future needs to consider a broader range of HPV types if these advances are to have a wider global impact.
TREATMENT ACCESS
- FDA approval of generic ARVs
- The last three issues of HTB included reports on antiretrovirals and treatment strategies, prevention of mother-to-child transmission (PMTCT), paediatrics, hepatitis coinfection, opportunistic infections and treatment access from this important conference.
- Access to generic efavirenz in South Africa: MSD agrees to grant licenses on reasonable terms
- TAC statement
- Even though efavirenz is not the preferred first-line option for treatment in South Africa, being reserved for nevirapine intolerance or contraindication, it accounts for over 60% of the total South African ARV drug budget.
- Reaching ‘3 by 5’…. by 7: new report on universal access
- On 2 June 2008, the World Health Organization (WHO), UNAIDS and UNICEF launched the joint report, ‘Towards Universal Access: Scaling up HIV Treatment, Care and Prevention Interventions in the Health Sector’.
- Oxfam criticises DFID’s new strategy as a “missed opportunity”
- As the government launched its new AIDS strategy for developing countries on 2 June, Oxfam was quick to praise the long-term commitment of substantial funding to strengthen health systems but expressed disappointment that the strategy lacked a specific spending target for tackling HIV and AIDS.
ANTIRETROVIRALS
- Boosted atazanavir approved in Europe as first-line therapy
- On 24th June 2008, the European Commission granted marketing authorisation for atazanavir boosted by ritonavir (300mg/100mg once daily), in combination with other antiretrovirals, as a first-line treatment HIV-1 infected adults. [1]
- BMS and Merck discontinue 100mg capsule formulation of efavirenz used for paediatric treatment
- Simon Collins, HIV i-Base
- In June 2007, the 100mg capsule formulation of efavirenz (Sustiva), was discontinued by Bristol-Myers Squibb (BMS), the European manufacturer and distributor. This alarmed UK doctors and pharmacists. Pharmacists only learnt of this through a news item in The Pharmaceutical Journal, rather than from any direct communication from BMS. This was without prior notification.
- Saquinavir (Invirase) interactions with digoxin, garlic capsules, methadone, tipranavir and omeprazole: US label changes
- Roche has updated their US package insert for saquinavir (Invirase) to include the following drug interaction information and include new warnings regarding coadministration of Invirase/ritonavir and digoxin (used in the treatment of various cardiac conditions).
- US label changes for nevirapine paediatric solution
- On 24 June 2008, FDA approved labeling changes to the Viramune (nevirapine) oral solution and tablets to reflect various updates
- New US pediatric dosing for lopinavir/r
- The lopinavir/r (Kaletra) tablet and oral solution labels were updated to include dosing recommendations for pediatric patients 14 days to 6 months of age and from 12 to 18 years of age.
- New US pediatric dosing for tipranavir/r
- On June 23, 2008, FDA approved a new Aptivus (tipranavir) oral solution (100 mg/mL). The product label has been updated to include dosing recommendations for pediatric patients 2-18 years of age.
- DSMB stops ACTG study due to suboptimal responses
- NIAID press release
- An independent Data and Safety Monitoring Board (DSMB) has determined that the experimental, once-daily antiretroviral drug regimen of FTC (emtricitabine), atazanavir and ddI enteric-coated (ddI-EC) is inferior to a standard antiretroviral drug regimen and therefore should be discontinued in an ongoing clinical trial. The National Institute of Allergy and Infectious Diseases (NIAID), the part of the National Institutes of Health that oversees the trial, concurs with this recommendation and has stopped this component of the study.
GUIDELINES
PREGNANCY & PMTCT
- Low rates of MTCT in UK and Ireland
- Polly Clayden, HIV i-Base
- A paper authored by Claire Townsend and co-workers published in the May 11, 2008 edition of AIDS reported very low rates of mother-to-child transmission (MTCT) of HIV in UK and Ireland, 2000-2006. [1]
PAEDIATRICS
- WHO recommends treating all HIV-infected infants aged less than 12 months
- Polly Clayden, HIV i-Base
- Following a meeting In April 2008 of the WHO Technical Reference Group for Paediatric HIV/Antiretroviral therapy and Care to consider the implications of recent research findings, the WHO have revised their guidelines for treatment and care of infants infected with HIV.
- Plasma concentrations and virologic evaluations after stopping NNRTI treatment in PENTA 11
- Polly Clayden, HIV i-Base
- A paper authored by Tim Cressey and co-workers from the PENTA-11 study group, published in the 15 May 2008 edition of Clinical Infectious Diseases, showed findings from an evaluation plasma concentrations, viral load, and development of drug resistance after a planned treatment interruption of a NNRTI–containing regimen in HIV-positive children.
BASIC SCIENCE AND VACCINE RESEARCH
- Elite control of a virus that caused AIDS in the transmitting partner
- Richard Jeffreys, TAG
- From the online first section of J. Virology, a new paper from Justin Bailey and colleagues provides evidence that a virus that is clearly pathogenic in one individual can be controlled in another. The paper describes a couple in which the male partner received an AIDS diagnosis 10 years ago after developing PCP and cerebral toxoplasmosis; he started antiretroviral treatment and recovered with a first documented CD4 count of 266 cells. The female partner tested HIV-positive at the same time, and had no other risk factors. She has since consistently maintained CD4 counts over 800 and a viral load of less than 50 copies/mL.
- Presentations from the May 21-23 HIV Vaccine Trials Network (HVTN) Meeting
- Of particular interest, Surojit Sarkar from Emory presents data indicating that - as suggested by the longitudinal data from trials of Merck’s HIV vaccine - CD8 T cell responses induced by Ad5 vectors do no contract in the way that typically occurs during the development of protective memory T cell responses, and that this is associated with the persistence of the vector. [2]
- Failure of STEP leads TAG to criticise the proposed PAVE100A vaccine trial
- Simon Collins, HIV i-Base
- The failure of STEP trial, using Merck’s adenovirus serotype 5 (Ad5)-based HIV vaccine, has implications for using another Ad5 candidate in the proposed PAVE100A Phase IIb efficacy trial.
OTHER NEWS
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EDITORIAL
- EDITORIAL: i-Base funding update
- First of all, thank you to everyone who wrote to the commissioners expressing your concern about our withdrawn TIPI funding. We are concerned that the standard reply that many of you received from Hong Tan is pretty misleading.
CONFERENCE REPORTS:
14th Annual BHIVA Conference
23–25 April 2008, Belfast
- Introduction
- HIV Treat Bull 2008 9(5/6);3
- The annual BHIVA spring conference has two main aims. In addition to presenting overview lectures on important aspects of HIV care and management - often given by international experts, it aims to encourage UK-based research and case studies by presenting research from junior doctors and researchers.
- Overview of MRC studies in 2008
- HIV Treat Bull 2008 May-Jun 9(5/6):3
- Simon Collins, HIV i-Base
- The first session at the conference included an overview of new Medical Research Council (MRC) adult studies that will start in 2008.
- Initial results of BHIVA audit of HIV-related inpatient and day care in the UK
- HIV Treat Bull 2008 May-Jun;9(5/6):5
- Simon Collins, HIV i-Base
- Annual audits on a wide range of aspects of HIV care and management are one of the most valuable aspects of BHIVA
programme of projects. Each year, they provide a snapshot of one or two evaluable areas, usually in reference recommendations
in BHIVA guidelines and standards.
- Monitoring patients on antiretroviral therapy in resource-limited settings with viral load,
CD4 count, or clinical observation alone
- HIV Treat Bull 2008 May-Jun;9(5/6):6
- Polly Clayden, HIV i-Base
- The majority of roll out programmes in resource-limited settings will introduce antiretrovirals using clinical monitoring without
viral load and often without monitoring of CD4 cell counts.
- Summary reports of other studies at BHIVA
- HIV Treat Bull 2008 May-Jun;9(5/6):8
- Simon Collins, HIV i-Base
- Effect of 100mg ritonavir once- and twice-daily on lipids and cardiovascular markers in HIV-negative volunteers: Carl Fletcher presented results from a study from the Chelsea and Westminster Hospital looking at the short-term impact of low-dose ritonavir on lipids, CD36 and other vascular inflammation markers (VIM) in 20 HIV-negative volunteers. The study looked at the relationship between drug exposure and these parameters.
CONFERENCE REPORTS
15th Conference on Retroviruses and Opportunistic Infections
Boston, 2-6 February 2008
- INTRODUCTION
- HIV Treat Bull 2008 May-Jun;9(5/6):10
- In this issue of HTB, we continue our extended coverage of this important meeting (see previous two issues of HTB for earlier reports.
CROI: OPPORTUNISTIC INFECTIONS
CROI: TREATMENT ACCESS
CROI: WOMEN’S HEALTH
- Gender differences in viral load by CD4 count in men and women
- HIV Treat Bull 2008 May-Jun;9(5/6):15
- Polly Clayden, HIV i-Base
- Previous research has found that CD4 count-adjusted viral load is approximately 0.2 log copies/mL greater in men compared to women. But these data have been largely limited to industrialised countries.
CROI: PAEDIATRIC CARE
- Immune reconstitution inflammatory syndrome in young children initiating ART
- HIV Treat Bull 2008 May-Jun;9(5/6):15
- Polly Clayden, HIV i-Base
- In an oral presentation Kelly Smith showed findings from a case note review of children enrolled in NEVEREST 2 (between April 2005 and November 2006), a South African trial in which HIV-positive children <2 years, exposed to nevirapine through PMTCT receive d4T/3TC/LPV/r (or RTV if <6 months). Children in this cohort receive BCG vaccination as a matter of routine. Often this occurs prior to HIV diagnosis.
- Complications with BCG vaccination in HIV-positive and negative infants: CHER Study
- HIV Treat Bull 2008 May-Jun;9(5/6):16
- Polly Clayden, HIV i-Base
- A poster from the CHER study group looked at Bacille-Calmette-Guerin (BCG)-related complications in this cohort and in a comparator group of HIV-negative infants born to mothers participating in a vaccine trial.
- The association between clinical characteristics and HIV-infection in very young infants
- HIV Treat Bull 2008 May-Jun;9(5/6):17
- Polly Clayden, HIV i-Base
- There are very few descriptions of characteristics of very young HIV-positive and HIV-exposed infants (<60 days). In settings with no access to PCR or CD4% quantification where clinical presumptive diagnosis is often used, these data could guide diagnostic algorithms for infants.
- Safety and efficacy of boosted darunavir in treatment-experienced children and adolescents at 24 weeks
- HIV Treat Bull 2008 May-Jun;9(5/6):18
- Polly Clayden, HIV i-Base
- In an oral late breaker Sabrina Spinosa-Guzman from Tibotec presented data for duranavir boosted with ritonavir (DRV/r) in a group of treatment experienced children and adolescents.
- Responses to atazanavir-containing HAART in treatment-naïve children in South Africa
- HIV Treat Bull 2008 May-Jun;9(5/6):19
- Polly Clayden, HIV i-Base
- A poster authored by Megan Palmer and coworkers from the United States and South Africa presented findings from PACTG 1020A. This is a phase I/II study of atazanavir (ATV) with or without ritonavir (r) with 2 NRTI (excluding tenofovir [TDF]) in HIV-positive treatment-naïve children aged 91 days to 21 years. This poster showed data from treatment-naïve South African children participating in the dose-finding study, for age (<2 years, 2 to 13 years, >13 years) and formulation (powder vs capsule) groups.
- Initial growth, CD4, and viral load responses to HAART in Ugandan compared to UK/Irish HIV-positive children
- HIV Treat Bull 2008 May-Jun;9(5/6):19
- Polly Clayden, HIV i-Base
- Children’s responses to ART in Africa may be different from children in well-resourced settings due to non-HIV-related factors including nutritional status, exposure to infections, food scarcity and malnutrition.
- Paediatric pharmacokinetic studies
- HIV Treat Bull 2008 May-Jun;9(5/6):20
- Polly Clayden, HIV i-Base
- Correct dosing of antiretrovirals in HIV-positive children is complicated due to age-dependent changes in pharmacokinetics (PK) and the scarcity of data.
- A pilot study of three treatment strategies for HIV-positive infants
- HIV Treat Bull 2008 May-Jun;9(5/6):24
- Polly Clayden, HIV i-Base
- In a late breaker presentation, Andrew Prendergast from the University of Oxford, described findings from a paediatric study conducted in KwaZulu Natal, by investigators from South Africa, UK and the US.
TREATMENT ACCESS
- Key patient safety concern removed in new FDA guidance for non-US trials
- HIV Treat Bull 2008 May-Jun;9(5/6):25
- The Helsinki Declaration issued by the World Medical Association (1989) was established to guide ethical principles of safety in clinical research and it is therefore extremely worrying that the FDA have removed one of the key recommendations from their guidance on US-based research that is carried out in poor countries.
- FDA approval of generic ARVs
- HIV Treat Bull 2008 May-Jun;9(5/6):25
- Since the last issue of HTB, the US Food and Drug Administration (FDA) has granted tentative approval for the following new generic ARV products.
ANTIRETROVIRALS
- Tibotec issue Dear Doctor letter and FDA require darunavir label change relating to hepatotoxicity
- HIV Treat Bull 2008 May-Jun;9(5/6):26
- In clinical trials and postmarketing experience, drug-induced hepatitis (e.g., acute hepatitis, cytolytic hepatitis) has been reported in patients receiving combination therapy with darunavir/r. Given the clinical relevance of this adverse reaction, the following information on hepatotoxicity has been added to the WARNINGS section of the darunavir prescribing information
- Draft BHIVA treatment guidelines online for comment
- HIV Treat Bull 2008 May-Jun;9(5/6):27
- The working draft of the 2008 BHIVA Guidelines have been posted online for comment. The draft has been revised to incorporate new information from peer-reviewed publications and conference abstracts from the last 2 years (including CROI 2008).
- Atazanavir 300mg capsule available
- HIV Treat Bull 2008 May-Jun;9(5/6):27
- A new 300 mg capsule of atazanavir (Reyataz) in now available in the UK for patients using combinations where 300 mg atazanavir is dosed with 100 mg ritonavir. This will reduce daily pill count by one for patients currently using the 150 mg capsule.
- Raltegravir approved in Scotland
- HIV Treat Bull 2008 May-Jun;9(5/6):27
- On 12 May the Scottish Medicines Consortium (SMC) announced that raltegravir (Isentress) has been accepted for restricted
use within NHS Scotland in combination with other antiretroviral medicinal products agents for the treatment of HIV-1 in
treatment-experienced adult patients with evidence of HIV-1 replication despite ongoing antiretroviral therapy.
- Abacavir, ddI and risk of heart attack: additional published
data and statements from the EMEA and FDA
- HIV Treat Bull 2008 May-Jun;9(5/6):27
- Simon Collins, HIV i-Base
- At the end of April, the Lancet published results from the D:A:D study looking at use of nucleosides and risk of myocardial infarction (MI). The same issue included correspondence from GSK on the findings from their trial database, and an editorial commentary on the interpretation of both studies.
- EDITORIAL
- This issue of HTB continues our coverage of the 15th Conference on Retroviruses and Opportunistic Infections with reports on antiretrovirals, treatment strategies, pregnancy and PMTCT, and hepatitis coinfection.
CONFERENCE REPORTS
CROI: ANTIRETROVIRALS
- Atazanavir/r vs lopinavir/r in treatment-naïve patients: 48 week results
- Simon Collins, HIV i-Base
- Although widely used off-label, atazanavir/r is not currently approved in Europe for use in first-line combinations, nor recommended in European guidelines, due to limited data in naïve patients. Results from a large randomised international head-to-head study against lopinavir/r, sponsored by BMS, are therefore important to report.
CROI: TREATMENT STRATEGIES
CROI: PREGNANCY AND MTCT
- Introduction to MTCT studies
- There were many studies to report on relating to pregnancy and MTCT at CROI this year and the studies below will add to our understanding of how to move forward.
- Very low rate of MTCT in women on HAART in UK and Ireland who achieve viral suppression
- Polly Clayden, HIV I-Base
- A poster from Claire Townsend and coworkers from the Institute of Child Health, St Thomas’ Hospital and St Mary’s Hospital looked at HIV mother to child transmission (MTCT) rates among women and infants in the UK and Ireland 2000 to 2006.
- Predictors of mother to child transmission among women initiating HAART in pregnancy in a South African cohort
- Polly Clayden, HIV I-Base
- There are limited data from Africa describing mother to child transmission (MTCT) in mothers initiating HAART in pregnancy.
- Maternal and infant outcomes from the DREAM programme
- Polly Clayden, HIV I-Base
- A poster from the Drug Resource Enhancement and Malnutrition (DREAM) programme reported 12-month mother and infant data from women initiating HAART in pregnancy and continuing throughout 6 months of breastfeeding in Mozambique. [1]
- Nevirapine-resistant HIV present in the latent reservoir following single-dose nevirapine for MTCT prevention
- Polly Clayden, HIV I-Base
- Nevirapine (NVP) resistant virus often becomes undetectable in the months after discontinuation of NNRTI therapy and after single dose MTCT prophylaxis. Until now, investigators have not determined whether or not resistant virus remains present in the latent reservoir in resting CD4 cells after single dose NVP exposure in HIV-infected women.
- Tenofovir plus FTC reduce NNRTI resistance following single dose nevirapine
- Polly Clayden, HIV I-Base
- Single dose nevirapine (NVP) still remains an important component in prevention of mother to child transmission (PMTCT). With short course AZT and “tail” coverage it is considered to be a reasonable option for women who do not need antiretroviral treatment to protect their own health.
- Response to treatment after single dose NVP exposure in women
- Polly Clayden, HIV I-Base
- In an oral presentation, Paul Weidle showed findings from a prospective cohort study of treatment response to an NNRTI-based regimen in women exposed or unexposed to single dose nevirapine for PMTCT. [1]
- Response to treatment after single dose NVP exposure in infants
- Polly Clayden, HIV I-Base
- A poster from Linda Barlow-Mosha and coworkers showed findings from an analysis of treatment response to a NVP-based regimen in HIV-positive Ugandan children, who were exposed or unexposed to single dose NVP at birth.
- Other studies looking at birth outcomes
- Polly Clayden, HIV I-Base
- Two posters looked at incidence of low birth weight and preterm birth in infants born to women receiving HAART.
- Infant prophylaxis for postnatal transmission
- Polly Clayden, HIV I-Base
- Two studies looked at giving prophylaxis to breastfed infants of HIV-positive mothers, who were negative at birth.
- Antiretroviral drug concentrations in breast milk and breastfeeding infants
- Polly Clayden, HIV I-Base
- A poster from the Breastfeeding, Antiretroviral, and Nutrition (BAN) study by Amanda Corbett and coworkers showed pharmacokinetic data in breast milk and plasma in mothers and breastfeeding infants.
- Maternal breastfeeding prophylaxis
- Polly Clayden, HIV I-Base
- The Kisumu Breastfeeding Study (KiBS), a phase IIB single-arm study evaluating maternal HAART for PMTCT in breastfeeding mothers in Kenya. In an oral presentation Timothy Thomas presented preliminary findings from KiBS. [1]
- Risk factors for breastfeeding transmission
- Two reports looked at risk factor for postnatal transmission.
CROI: HEPATITIS COINFECTION
- UK cohort reports sexual HCV reinfection in at least 5% HIV-positive gay men following sustained response to treatment
- Simon Collins, HIV i-Base
- Rachel Jones form Chelsea and Westminster Hospital presented an analysis of failed treatment of HCV in HIV-positive gay men. Describing the characteristics of individuals with a second episode of HCV viraemia following SVR post-treatment of HCV, using molecular phylogenic analysis to determine whether viraemia was due to treatment relapse or secondary infection.
- MELD score predictive of pre-transplant mortality in HCV coinfected patients
- Simon Collins, HIV i-Base
- Aruna Subramanian form Johns Hopkins University looked at determining incidence, cause, and time to pre-transplant mortality in transplant candidates compared to HIV-negative patients in a prospective cohort study at 20 US sites, with particular reference to the MELD score.
- Does abacavir decrease SVR rates with HCV treatment?
- Simon Collins, HIV i-Base
- Three studies from Spain reported on the relationship between nucleoside/tide analogues and response to HCV treatment. [1, 2, 3] Last year at CROI, a poster from French researchers reported that abacavir use was significantly associated with poorer outcome to HCV treatment, through a possible intracellular competition between abacavir and ribavirin. [4]
- No effect of interferon maintenance therapy on fibrosis progression in non-responders
- Simon Collins, HIV i-Base
- One aspect of HCV management that is informed by little data, is whether continued treatment of virologic non-responders with maintenance peg-IFN therapy can reduce the rate of clinical HCV progression.
CROI: BASIC SCIENCE
CROI: ONCOLOGY
TREATMENT ACCESS
ANTIRETROVIRALS
IMMUNOLOGY AND BASIC SCIENCE
- A gutsy talk, and a new paper: report from third workshop on HIV persistenceRichard Jeffreys, TAG basic science log
- Richard Jeffreys, TAG basic science log
- In December 2007, the third workshop on HIV persistence during therapy took place on the Caribbean island of St. Maarten, where the weather is sunnier than prospects for eradicating HIV infection currently appear to be. [1] The meeting is the brainchild of French researcher Alan Lafeuillade and aims to bring together researchers interested in the topic of curing HIV infection, either by eradication or inducing lifelong control or tolerance of the virus without the need for ongoing drug therapy.
OTHER NEWS
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- EDITORIAL
- Welcome to the first issue of HTB for 2008. Every new year it is always a little sobering to find that we are still producing HTB - and that this year we are startng volume 9.
CONFERENCE REPORTS
- 15th Conference on Retroviruses and Opportunistic Infections
- 2-6 February 2008, Boston
- This annual conference is one of the most important annual scientific meetings.
- Increased risk of myocardial infarction associated with abacavir and ddI
- Simon Collins, HIV i-Base
- A poster presented by Caroline Sabin from the Royal Free Hospital looked at whether nucleoside analogues were associated with cardiovascular disease (CVD) seen in the large international D:A:D cohort study. [1] D:A:D includes over 33,000 patients from 11 prospective cohorts, in which 517 myocardial infarctions (MI) occured over approximately seven years of follow up (157,912 patient years).
- Position statement by the D:A:D steering committee
- Regarding: Abstract entitled “Do Thymidine Analogues, Abacavir, Didanosine and Lamivudine Contribute to the Risk of Myocardial Infarction (MI)? (vis a vis: Recent Use of Abacavir and Didanosine, but not of Thymidine Analogues, Is Associated with Risk of Myocardial Infarction): the D:A:D Study” presented at Conference on Retroviruses and Opportunistic Infections (CROI), Boston, 2008.
CONFERENCE REPORTS
CONFERENCE REPORTS
- 3rd International Workshop on Targeting HIV Entry
- 7-9 December 2007, Washington DC
- An enhanced coreceptor tropism assay from Monogram Biosciences spotted HIV that can use the CXCR4 (X4) receptor on CD4 cells in 5 of 59 people (8.5%) just diagnosed with HIV infection [1]. In all 5 people the X4-using virus persisted throughout follow-up, while X4 virus became detectable in several study participants during the early years of infection.
- Background drugs and low maraviroc levels explain resistance in Motivate studies
- Mark Mascolini, for NATAP
- Having only one or no active drugs in the background regimen explained emergence of virus resistant to the CCR5 antagonist maraviroc in the salvage trials MOTIVATE 1 and 2, according to new work by Pfizer researchers [1]. All 4 people in whom maraviroc-resistant virus emerged during the study had low concentrations of the drug.
TREATMENT ACCESS
- Boehringer fails to register tipranavir in Brazil after using Brazilian patients in registrational study
- Boehringer Ingelheim, the manufacturer of tipranavir, has refused to launch the drug in Brazil because it disagrees with the patent law of the country. By not registering the medicine in the country, it is difficult for treatment-experienced patients who need this potentially life-saving protease inhibitor, to access it. No medicine can be sold, offered by the Public Health System - without registration.
- FDA approval of generic ARVs
- Since the last issue of HTB, the US Food and Drug Administration (FDA) has granted tentative approval for the following new generic ARV products.
ANTIRETROVIRALS
- Raltegravir approved in Europe and available in the UK
- On 23 January 2008, raltegravir, the first antiretroviral integrase inhibitor manufactured by Merck, was granted European approval. [1] Results from registrational studies have been previously reported in HTB. [2, 3]
- Paediatric lopinavir/r receives positive opinion from EMEA
- On 28 January, 2008 Abbott announced that the European Committee for Medicinal Products for Human Use (CHMP), the scientific committee of the European Medicines Agency (EMEA), has issued a positive opinion recommending approval of a new, lower-strength tablet formulation of lopinavir/r (Kaletra,). The CHMP also adopted a positive opinion, in coordination with the World Health Organization (WHO), for the same lower-strength formulation in developing countries (trade name Aluvia).
- Etravirine (TMC-125) approved in the US
- On 18 January 2008, the Food and Drug Administration (FDA) granted accelerated approval for etravirine 100 mg tablets. [1]
- Changes to atazanavir product label in US
- The US atazanavir (Reyataz) package insert was revised to include information regarding the administration of atazanavir and/or atazanavir/ritonavir with food, proton pump inhibitors, H2 receptor antagonists, acetaminophen, and fluconazole. Additionally, dosing information in patients with renal impairment was included.
- US treatment guidelines updated
- The US Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents have been updated to include significant changes in some recommendations, even though the last major update was in December 2007. The latest updates include new sections on what to start, treatment interruptions, TB/HIV coinfection, and acute HIV infection.
- HIV-positive adults with CD4 >500 cells/mm3 have similar mortality rates as the general population after seven years ARV treatment
- Charlotte Lewden and colleagues published an analysis of life-expectancy in a subgroup of patients on long-term PI-based HAART, from two French cohorts, in the September 2007 edition of JAIDS.
RESISTANCE
PREGNANCY AND PMTCT
- Atazanavir exposure in pregnancy
- Polly Clayden, HIV i-Base
- A paper authored by Ripamonti Diego from the Division of Infectious Diseases, Ospedali Riuniti, Bergamo, Italy and coworkers, published in the November 30 edition of AIDS, reported findings from a study looking at the pharmacokinectics and placental transfer of boosted atazanavir in a group of HIV-positive pregnant women.
- Two-dose versus monthly intermittent preventive treatment of malaria with sulfadoxine-pyrimethamine in HIV-positive pregnant women
- Polly Clayden, HIV i-Base
- Malaria during pregnancy carries risks of maternal mortality and anaemia and foetal mortality, growth retardation, preterm birth and low birth rate. HIV-positive pregnant women have greater risk of malarial parasitemia, higher parasite densities, higher anaemia rates and more frequent placental infections and birth complications than HIV-negative women.
PAEDIATRICS
- Predictors of mortality in untreated HIV-positive children
- Polly Clayden, HIV i-Base
- The Cross Continents Collaboration for Kids (3Cs4kids) performed a meta analysis of children aged 12 months and older from 10 studies (nine African, one Brazilian) to evaluate the predictive value of laboratory and growth markers on the short term mortality risk in untreated HIV-positive children.
- Pharmacokinetics of lopinavir/ritonavir in infants less than 12 months of age
- Polly Clayden, HIV i-Base
- A paper published in the January 11 edition of AIDS reported findings from an evaluation of the pharmacokinetics, safety and efficacy of lopinavir/ritonavir (LPV/r)-based treatment in HIV-positive infants 6 weeks to 6 months of age. This multicentre trial was conducted by the Pediatric AIDS Clinical Trials Group (PATCG) in the United States and Brazil . The study is a prospective, open label, phase I/II trial with planned 48 week follow up. These findings were from an interim evaluation at 24 weeks.
HEPATITIS COINFECTION
IMMUNOLOGY AND BASIC SCIENCE
- An overview of recent news from Richard Jeffreys Basic Science blog.
- Richard Jeffreys, TAG
- An important new study has just been published in Science Express, the advance online section of the widely read journal Science. Abraham Brass and colleagues report results obtained using a genome-wide screen for host proteins necessary for HIV replication. The researchers used an approach that involves blocking the activity of known human genes using small slices of RNA called small interfering RNAs (siRNAs). A staggering 21,121 pools of four siRNAs per gene were employed in the study, ultimately revealing 273 host proteins that appear necessary for efficient HIV replication (the researchers have dubbed them “HIV dependency factors” or HDFs). [1]
DRUG INTERACTIONS
ON THE WEB
- Conference reports:
- Targeting HIV Entry: 3rd International Workshop
- Online journal articles:
- Three free access papers from the online first section of the Journal of Infectious Diseases. The articles highlight the role of CCR5 - better known as a co-receptor for HIV entry into cells - in T cell trafficking to sites of infection and suggest that studies are needed to evaluate the effects of pharmacological inhibition of CCR5 in these settings.
- Online medical resources:
- A new website from the organisation Centres for Reproductive Assistance Techniques in HIV in Europe (CREATHE), is aimed at improving the access to safer conception methods for people living with HIV.
This information is designed to support, not replace, the relationship that exists between you and your doctor.
©1980-2008. AEGiS.