New Publications in HIV : Archive

20 April 2009

HIV monotherapy with ritonavir-boosted protease inhibitors: a systematic review.

Bierman WFW et al. AIDS 2009;23:279–91. Jan Systematic review of all PI monotherapy studies to assess the efficacy of ritonavir-boosted PI monotherapy.

Conclusions: The overall efficacy of ritonavir-boosted PI monotherapy is inferior to HAART. The efficacy improves in patients started on monotherapy after suppressed HIV-RNA for at least 6 months. The majority of patients with prolonged viral suppression on HAART can successfully be treated with PI monotherapy.
Link 20 April 2009

Cost-effectiveness analysis of lopinavir/ritonavir and atazanavir+ritonavir regimens in the CASTLE study.

Simpson KN et al. 2009 Feb 14. [Epub ahead of print] Cost-effectiveness and budget-impact analysis comparing LPV/r and ATV/r for ARV-naïve patients.

Use of the LPV/r regimen saved $24,518 and $36,651 at 5 and 10 years, respectively, with lifetime cost savings estimated at $38,490.

Conclusion: In the CASTLE study, an LPV/r-based regimen in ARV-naïve patients appears to be more cost-effective than an ATV/r-based regimen. The very small added CHD risk predicted by LPV/r treatment is more than offset by the substantial short- and long-term cost savings.
Link 20 April 2009

Gemini: a noninferiority study of saquinavir/ritonavir versus lopinavir/ritonavir as initial HIV-1 therapy in adults.

Walmsley S et al. J Acquir Immune Defic Syndr 2009 Feb 12. [Epub ahead of print] This, randomised, open-label, non-inferiority study compared SQV/r 1000 mg/100 mg twice daily and LPV/r 400 mg/100 mg twice daily, each with FTC/TDF 200 mg/300 mg every day.

SQV/r was noninferior to LPV/r: a similar proportion of patients had HIV-1 RNA levels <50 copies per mL at week 48 (64.7% vs 63.5%; estimated difference in proportion for noninferiority 1.14%; 96% CI –9.6 to11.9; p<0.012).

Conclusion: SQV/r was non-inferior to LPV/r in terms of virologic suppression at 48 weeks and had a better triglyceride profile in treatment-naïve patients.
Link 20 April 2009

Effect of nucleoside reverse transcriptase inhibitors on CD4 T-cell recovery in HIV-1-infected individuals receiving long-term fully suppressive combination antiretroviral therapy.

Byakwaga H et al. HIV Med 2009;10:143–51. March This retrospective cohort study assessed the effect of NRTIs on CD4 cell recovery in patients receiving long-term combination ART.

Conclusion: Exposure to different NRTIs in initial combination ART was not significantly associated with increases in CD4 cell count.
Link 20 April 2009

Tenofovir se in human immunodeficiency virus-1-infected children in the United Kingdom and Ireland.

Riordan A et al. Pediatr Infect Dis J 2009;28:204–9. This study analysed the use of TDF in a cohort of HIV-1-infected children.

159 of 1253 children had taken TDF: 18% received >120% and 37% received <80% of the suggested paediatric dose (8 mg/kg). Twelve (7.5%) children experienced serious adverse events and stopped TDF permanently, 11 taking concurrent lopinavir-ritonavir, and 10 ddI; five had renal toxicity.

Conclusions: TDF seems to be an effective ARV in this paediatric cohort but considerable underdosing and overdosing occurs and a small number of children experienced serious adverse events.
Link 23 April 2009

Benefits and risks of stavudine therapy for HIV-associated neurologic complications in Uganda.

Sacktor N et al. Neurology 2009;72:165–70. • This study investigated the risk/benefit of stavudine-based HAART for HIV-associated cognitive impairment and distal sensory neuropathy.
• Conclusion: Treatment was associated with improvement in verbal memory, motor and psychomotor speed, executive thinking, and verbal fluency. However, neuropathy symptoms developed in 38% of previously asymptomatic HIV+ patients.
Link 23 April 2009

Cost-effectiveness analysis of lopinavir/ritonavir and atazanavir+ritonavir regimens in the CASTLE study.

Simpson KN et al. 2009 Feb 14. [Epub ahead of print] • Cost-effectiveness and budget-impact analysis comparing LPV/r and ATV/r for ARV-naïve patients.
• Use of the LPV/r regimen saved $24,518 and $36,651 at 5 and 10 years, respectively, with lifetime cost savings estimated at $38,490.
• Conclusion: In the CASTLE study, an LPV/r-based regimen in ARV-naïve patients appears to be more cost-effective than an ATV/r-based regimen. The very small added CHD risk predicted by LPV/r treatment is more than offset by the substantial short- and long-term cost savings.
Link 28 April 2009

Effect of nucleoside reverse transcriptase inhibitors on CD4 T-cell recovery in HIV-1-infected individuals receiving long-term fully suppressive combination antiretroviral therapy.

Byakwaga H et al. HIV Med 2009;10:143–51.March • This retrospective cohort study assessed the effect of NRTIs on CD4 cell recovery in patients receiving long-term combination ART.
• Conclusion: Exposure to different NRTIs in initial combination ART was not significantly associated with increases in CD4 cell count.
Link 28 April 2009

Tenofovir se in human immunodeficiency virus-1-infected children in the United Kingdom and Ireland

Riordan A et al. Pediatr Infect Dis J 2009;28:204–9. • This study analysed the use of TDF in a cohort of HIV-1-infected children.
• 159 of 1253 children had taken TDF: 18% received >120% and 37% received <80% of the suggested paediatric dose (8 mg/kg). Twelve (7.5%) children experienced serious adverse events and stopped TDF permanently, 11 taking concurrent lopinavir-ritonavir, and 10 ddI; five had renal toxicity.
• Conclusions: TDF seems to be an effective ARV in this paediatric cohort but considerable underdosing and overdosing occurs and a small number of children experienced serious adverse events.
Link 28 April 2009

Hepatotoxicity associated with long versus short-course HIV-prophylactic nevirapine use. A systematic review and meta-analysis from the research on Adverse Drug events And Reports (RADAR) Project.

McKoy JM et al. Drug Saf 2009;32:147–58. Feb • A review of hepatotoxicity cases among HIV-negative individuals and HIV-positive pregnant women and their offspring receiving short- (≤4 days) versus long-course (≥5 days) NVP prophylaxis.
• Long-course NVP was associated with a greater incidence of hepatotoxicity then short-course NVP in all the patient groups studied.
• Conclusions: The duration of NVP therapy appears to significantly predict hepatotoxicity.
Link 28 April 2009

Raltegravir: the first HIV type 1 integrase inhibitor.

Hicks C, Gulick RM. Clin Infect Dis 2009;48:931–9. • Review of raltegravir, the first approved INI, which targets the strand transfer step of HIV-1 integration.
• Clinical trials have shown that raltegravir-containing regimens have potent ARV activity and are well tolerated in HIV-1-infected patients. Drug resistance, conferred by substitutions in the gene coding for the HIV-1 integrase enzyme, develops relatively frequently after VF.
• Conclusion: Raltegravir represents an important advance in treatment options for HIV-1.
Link 29 April 2009

Raltegravir and etravirine are active against HIV type 1 group O.

Briz V et al. AIDS Res Hum Retroviruses 2009;25:225–7. • This study investigated the activity of raltegravir and etravirine against HIV-1 group was assessed in vitro and in vivo.
• Both drugs showed significant in vitro antiviral activity. Raltegravir showed clinical benefit in an HIV-1 group O-infected individual.
• Conclude: Individuals infected with HIV-1 group O might benefit from raltegravir and/or etravirine therapy.
Link 06 May 2009

Etravirine, a next-generation nonnucleoside reverse-transcriptase inhibitor.

Johnson LB, Saravolatz LD. Clin Infect Dis 2009;48:1123–8. • This article reviews ETV’s in-vitro activity against WT and NNRTI-resistant HIV strains, in-vitro resistance and treatment failure, clinical studies showing the benefit of adding ETV to an optimised background regimen in patients with VF and multidrug-resistant HIV and major adverse events. Link 06 May 2009

Etravirine and rilpivirine: nonnucleoside reverse transcriptase inhibitors with activity against human immunodeficiency virus type 1 strains resistant to previous nonnucleoside agents.

Fulco PP, McNicholl IR. Pharmacotherapy 2009;29:281–94. • A review article of ETV and rilpivirine. Link 06 May 2009

Safety and efficacy of nevirapine- and efavirenz-based antiretroviral treatment in adults treated for TB-HIV co-infection in Botswana.

Shipton LK et al. Int J Tuberc Lung Dis 2009;13:360–6. • This retrospective study compared HIV-positive adults with and without TB treatment who received NVP- or EFV-based ART.
• There was no difference in virological or immunological response during the first year of ART, even when NVP and EFV patients were stratified by TB treatment exposure.
• Conclusions: Both NVP- and EFV-based ART were effective in patients co-infected with HIV and TB. Hepatotoxicity was more common in patients who received TB treatment, so liver-function tests should be monitored closely.
Link 06 May 2009

Response to zidovudine/didanosine-containing combination antiretroviral therapy among HIV-1 subtype C-infected adults in Botswana: two-year outcomes from a randomized clinical trial.

Bussmann H et al. J Acquir Immune Defic Syndr 2009 Mar 11. [Epub ahead of print] • The Tshepo study was a randomized open-label trial in treatment-naïve, HIV-1 subtype C-infected adults that compared the efficacy and tolerability PI-sparing combination ARV with NRTIs (ZDV+3TC, ZDV+ddI and d4T+3TC) and NNRTIs (NVP and EFV) and different adherence strategies (standard care versus an intensified adherence strategy)
• The ZDV/ddI arms were discontinued due to inferiority in the primary endpoint (VF and resistance).
• The proportion of patients with VF and genotypic resistance mutations was 11% for ZDV/ddI-based ART versus 2% in those receiving either ZDV/3TC- or d4T/3TC-based ART (p=0.002).
• Conclusions: The preliminary results showed that NNRTI-based ART had excellent efficacy and tolerability in HIV-1 subtype C-positive adults. However, ZDV/ddI-containing ART was inferior to the dual NRTIs d4T/3TC or ZDV/3TC when used with an NNRTI as first-line ART.
Link 06 May 2009

Association of non-cirrhotic portal hypertension in HIV-infected persons and ART with didanosine.

Kovari H et al. CROI 2009;Abstract 751. • This nested case-control study investigated possible risk factors for cryptogenic non-cirrhotic portal hypertension (NCPH).
• In bi-variable models, only the association of NCPH with ddI exposure was robust; other co-variables, particularly low CD4 cell count, were not independent risk factors.
• Conclusion: There was a strong association with prolonged exposure to ddI and the development of NCPH.
Link 07 May 2009

Nevirapine pharmacokinetics in HIV-infected and HIV/HCV-coinfected individuals.

Vogel M et al. J Antimicrob Chemother 2009 Mar 6. • This study investigated the differences in NVP pK between patients with HIV infection and HIV/HCV co-infection that could be responsible for higher rates of hepatotoxicity.
• No difference was observed between the two groups in minimum and maximum drug levels or total drug exposure in terms of area under the curve.
• Conclusion: HCV co-infection does not alter the NVP pK in patients with preserved liver function.
Link 07 May 2009

Kidney tubular abnormalities in the absence of impaired glomerular function in HIV patients treated with tenofovir.

Labarga P et al. AIDS 2009;23:689–96. • This study investigated plasma and 24-hour urine markers of kidney tubulopathy in patients on TDF-containing HAART, patients on non-TDF HAART and ARV-naïve individuals.
• There were no significant differences in creatinine clearance between the three groups. The only independent predictors of tubular dysfunction were TDF use (p<0.001) and older age (p= 0.01).
• Conclusions: TDF is associated with an increased risk of kidney tubular abnormalities in the absence of significant impaired glomerular function. The long-term consequences of this tubulopathy are unknown.
Link 14 May 2009

A Once-Daily Lopinavir/Ritonavir-Based Regimen Is Noninferior to Twice-Daily Dosing and Results in Similar Safety and Tolerability in Antiretroviral-Naive Subjects Through 48 Weeks.

Gathe J et al. J Acquir Immune Defic Syndr 2009;50:474–81. • This study compared od and bid dosing of LPV/r plus TDF and FTC od in ARV-naïve patients.
• At week 48, 77% of od vs 76% of bid patients had HIV-1 RNA <50 copies/mL (p=0.715; 95% CI: 5–8%). Response rates, discontinuation rates and adverse events were similar in both groups.
• Conclusions: The response to LPV/r od was noninferior to bid dosing with comparable efficacy and safety. No new PI resistance mutations were detected on virologic rebound.
Link 14 May 2009

Scaleable manufacture of HIV-1 entry inhibitor griffithsin and validation of its safety and efficacy as a topical microbicide component.

O'Keefe BR et al. Proc Natl Acad Sci U S A. 2009 Mar 30. • This study reports a manufacturing breakthrough for griffithsin, a red algal protein that is a potent microbicide entry inhibitor.
• Griffithsin was produced in multi-gram quantities after extraction from Nicotiana benthamiana plants transduced with a tobacco mosaic virus vector expressing griffithsin. Plant-produced griffithsin was shown to be active against HIV at picomolar concentrations, was non-irritating and non-inflammatory and has broad-spectrum activity against HIV clades A, B, and C.
• Conclusion: plant-produced griffithsin has potential as a microbicide component for HIV prevention.
Link 14 May 2009

Anti-HIV drugs: 25 compounds approved within 25 years after the discovery of HIV.

De Clercq E. Int J Antimicrob Agents 2009;33:307–20. • This article reviews the 25 anti-HIV compounds have been approved for the treatment of HIV/AIDS in the 25 years since HIV was discovered.
• Conclusion: These agents should be used in combination regimens to achieve the best efficacy, tolerability and compliance and to reduce the risk of developing resistance.
Link 14 May 2009

Population pharmacokinetics of ritonavir-boosted atazanavir in HIV-infected patients and healthy volunteers.

Back D et al. J Antimicrob Chemother 2009 Mar 28. [Epub ahead of print] • This study reports the development and validation of a population pharmacokinetic model to describe ATV/r concentrations (300/100 mg once daily), identify important covariates and evaluate the predictive performance of the model for lower, unlicensed ATV doses (150 and 200 mg once daily) boosted with ritonavir (100 mg once daily).
• A one-compartment model with first-order absorption and lag-time best described the data. RTV AUC0–24 was the only significant covariate. Overall, 94–97% of observed concentrations were within the 95% prediction intervals for all three regimens.
• Conclusions: RTV AUC0–24 was significantly associated with ATV apparent oral clearance.
Link 14 May 2009

Bone pain due to fractures revealing osteomalacia related to tenofovir-induced proximal renal tubular dysfunction in a human immunodeficiency virus-infected patient.

Perrot S, Aslangul E, Szwebel T et al. J Clin Rheumatol 2009;15:72–4. • This study reports a case of chronic metabolic complications with bone fractures related to TDF.
• Several factors increased the renal toxicity of TDF including low BMI, concomitant use of NSAIDs, and other ARVs, including RTV.
Link 14 May 2009

Safe substitution to zidovudine among HIV-infected patients initiated on stavudine-containing highly active antiretroviral therapy from a resource-limited setting.

Kumarasamy N, Venkatesh KK, Devaleenol B et al. Int J Infect Dis 2009 Mar 26. [Epub ahead of print] • This retrospective study in Southern India investigated the substitution of d4T with AZT in patients who started d4T-based HAART due to the development of anaemia.
• During the study period, half of 619 patients who started d4T-based HAART subsequently received AZT. After substitution, three patients (2.7%) who substituted after <6 months and one patient (0.6%) who substituted between 6–12 months developed anemia. Patients who substituted after <6 months had significantly higher median CD4-cell counts at 1- and 6-month follow-up than patients who substituted at 6–12 months (p<0.05).
• Conclusion: In settings where TDF is either expensive or not available, starting d4T followed by prompt substitution with AZT can be a safe option for anaemic patients.
Link 15 May 2009

Kidney tubular abnormalities in the absence of impaired glomerular function in HIV patients treated with tenofovir.

Labarga P, Barreiro P, Martin-Carbonero L et al. AIDS 2009;23:689–96. • This study investigated renal function in three patient groups: TDF-containing HAART (1); HAART never exposed to TDF (2); and ARV-naïve (3).
• No significant differences in CrCl were observed between the groups. The proportion of patients with tubular damage in groups 1, 2 and 3 was 22%, 6% and 12%, respectively. In a multivariate analysis, the only independent predictors of tubular dysfunction were TDF use (OR: 21.6; 95% CI: 4.1–113; p<0.001) and older age (OR: 1.1 per year; 95% CI: 1.0–1.1; p=0.01).
• Conclusions: TDF is associated with an increased risk over time of kidney tubular abnormalities in the absence of significant impaired glomerular function. Periodic screening of tubular function parameters should be recommended to patients receiving TDF.
Link 15 May 2009

A delayed hypersensitivity reaction to enfuvirtide after rechallenge.

Emerson CR, Post JJ, Workman C. Int J STD AIDS 2009;20:288–9. • This is the first case report of a delayed hypersensitivity reaction to ENF.
• A highly ARV-experienced man was started on a new ENF-containing regimen together with TMP-STX prophylaxis for Pneumocystis jirovecii pneumonia. A maculopapular rash on the chest and abdomen without any systemic features developed 10 days later. Both ENF and TMP-STX were discontinued and re-introduction of ENF occurred in a hospital setting. The rash re-appeared involving the whole body 5 hours post-dose and was associated with fever, nausea and a presyncopal episode.
Link 05 June 2009

Changes in body composition with ritonavir-boosted and unboosted atazanavir treatment in combination with lamivudine and stavudine: a 96-week randomized, controlled study.

McComsey G, Rightmire A, Wirtz V et al. Clin Infect Dis 2009;48:1323–6. • This open-label, randomized study investigated changes in body composition in treatment-naïve patients treated with either ATV or RTV-boosted ATV in combination with d4T and 3TC.
• Both groups had similar increases in trunk fat but there was a significantly lower incidence of lipoatrophy in patients treated with RTV-boosted ATV.
Link 08 June 2009

A randomized, controlled trial of initial anti-retroviral therapy with abacavir/lamivudine/zidovudine twice-daily compared to atazanavir once-daily with lamivudine/zidovudine twice-daily in HIV-infected patients over 48 weeks (ESS100327, the ACTION Study)

Kumar PN, Salvato P, Lamarca A et al. AIDS Res Ther 2009 Apr 9;6:3. • The ACTION study investigated whether alternate treatment options may meet the needs of both general and special patient populations for whom traditional first-line regimens are unsuitable.
• This 48-week study compared the safety and efficacy of a triple NRTI regimen (ABC/3TC/ZDV twice daily) with a PI plus dual NRTI regimen (ATV once daily + 3TC/ZDV twice-daily) in treatment-naïve patients.
• ABC/3TC/ZDV was non-inferior to ATV+3TC/ZDV, with 62% vs 59% of patients achieving a VL <50 copies/mL at week 48 (95% CI –5.9–10.4). Similar results were observed in patients with baseline VL<100,000 copies/mL (66% vs 59%; 95% CI: –5.6–19.5). However, the non-inferiority criterion was not meet in patients with baseline VL ≥100,000 copies/mL (39% vs 60%; 95% CI: –49.2–7.4).
• Conclusions: ABC/3TC/ZDV demonstrated comparable virological efficacy to ATV+3TC/ZDV. In patients with a baseline VL ≥100,000 copies/mL, ATV+3TC/ZDV showed better virological efficacy.
Link 08 June 2009

The nucleoside backbone affects durability of efavirenz- or nevirapine-based highly active antiretroviral therapy in antiretroviral-naive individuals.

Annan NT, Nelson M, Mandalia S et al. J Acquir Immune Defic Syndr 2009 Apr 6. [Epub ahead of print] • This study investigated the efficacy of NNRTI-based regimens (NVP or EFV) and the effect of year treatment started, NRTI backbone, sex and ethnicity on treatment outcome in ARV-naïve patients starting HAART.
• Of 994 patients, 73% started EFV- and 27% NVP-based regimens. There was no difference between the two groups for virological success (EFV, 71%; NVP, 72%; p=0.77) or treatment failure (EFV, 23%; NVP, 26%; p=0.58).
• The year HAART was started was significantly associated with virological success and treatment failure (p<0.001). The likelihood of virological success for d4T/3TC was 52% [HR: 1.52; 95% CI: 1.17–1.97; p=0.002]. The non-thymidine analogues were least likely to be associated with virological success (HR: 0.62; 95% CI: 0.48–0.80; p<0.001). Sex and ethnicity were not associated with treatment outcome.
• Conclusions: There was no significant difference between NVP and EFV for time to virological success or treatment failure. Year of starting HAART and NRTI backbones were significant predictors of virological success and treatment failure.
Link 08 June 2009

Clinical experience with the combined use of lopinavir/ritonavir and rifampicin.

L'homme RF, Nijland HM, Gras L et al. AIDS 2009;27:863–5. • In this study of 34 patients treated concomitantly with LPV/r and rifampicin, only 15% used the recommended increased dose of LPV/r.
• Of the patients on a non-adjusted dose of LPV/r, 67% had a sub-therapeutic LPV plasma concentration and 38% had a detectable VL.
• Forty percent of patients on an increased dose of LPV/r prematurely stopped the drug combination because of adverse events.
• Conclusion: Combined use of LPV/r and rifampicin is challenging because there has to be a balance between suboptimal efficacy and toxicity.
Link 08 June 2009

Maraviroc: perspectives for use in antiretroviral-naive HIV-1-infected patients.

Vandekerckhove L, Verhofstede C, Vogelaers D. J Antimicrob Chemother 2009 Apr 18. [Epub ahead of print] • This article reviews the prospective and retrospective analyses of the MERIT data and highlights the impact of these results on the use of maraviroc in clinical practice.
• Due to its mode of action, it is expected that maraviroc will be effective only in a subpopulation of patients harbouring the R5 virus.
• Maraviroc has not met the criteria of potency, durability and convenience in a prospective analysis required for first-line regimens and cannot be advocated for clinical use in treatment-naive patients.
• Whether maraviroc can be used together with other drugs with a low genetic barrier, such as non-nucleoside analogues or integrase inhibitors in first-line regimens is currently unclear.
• The favourable lipid profile and tolerability support the use of maraviroc as a safe alternative in a consolidation or maintenance regimen after achieving full virological suppression, especially in patients experiencing side effects on NNRTIs, PIs or integrase inhibitors.
Link 09 June 2009

Response to zidovudine/didanosine-containing combination antiretroviral therapy among HIV-1 subtype C-infected adults in Botswana: two-year outcomes from a randomized clinical trial.

Bussmann H, Wester CW, Thomas A et al. J Acquir Immune Defic Syndr. 2009;51:37–46. • The Tshepo study compared the efficacy and tolerability of three NRTI combinations (ZDV+3TC, ZDV+ddI and d4T+3TC) and two different NNRTIs (NVP and EFV) and two different adherence strategies (the current standard of care and an ‘intensified adherence strategy).
• The ZDV+ddI arms were discontinued due to inferiority in the primary endpoint (VF with resistance).
• VF and genotypic resistance mutations occurred in 11% of patients receiving ZDV+ddI-based ART versus 2% in patients receiving either ZDV+3TC- or d4T+3TC-based ART (p=0.002).
• The median CD4-cell count increase at 1 and 2 years was 137 and 199 cells/mm3 and the percentage of patients with plasma HIV-1 RNA level ≤400 copies/mL was 92.0% and 88.8%.
• Kaplan–Meier survival estimates at 1 and 2 years were 96.6% and 95.4%. One hundred and twenty patients (18.2%) had treatment-modifying toxicities: the most common were lipodystrophy, anaemia, neutropenia, and Stevens–Johnson syndrome.
• Conclusions: The preliminary results show overall excellent efficacy and tolerability of NNRTI-based ART among HIV-1 subtype C–infected adults. However, ZDV+ddI is inferior to d4T+3TC or ZDV+3TC when used with an NNRTI for first-line ART.
Link 09 June 2009

Expanding the frontiers of existing antiviral drugs: possible effects of HIV-1 protease inhibitors against SARS and avian influenza.

Savarino A. J Clin Virol 2005;34:170–178. • This article discusses the evidence that PIs might have effects on SARS and avian influenza.
• Evidence for the potential benefits of PIs against the SARS coronavirus comes from empirical clinical studies, in vivo viral inhibition assays and computational simulations of the docking of these compounds to the active site of the main SARS coronavirus protease.
• There is also a remote possibility that PIs may have effects on avian influenza viruses.
• Conclusion: PIs should be considered for further testing as potential therapeutic agents for SARS and avian influenza.
Link 09 June 2009

Identification of nevirapine-resistant HIV-1 in the latent reservoir after single-dose nevirapine to prevent mother-to-child transmission of HIV-1.

Wind-Rotolo M, Durand C, Cranmer L, et al. J Infect Dis 2009;199:1301–1309. • This study investigated NVP resistance in women from South Africa and Uganda >6 months after they had received single-dose NVP for prevention of mother-to-child transmission of HIV-1.
• Although only a small number of latently infected cells were present in each blood sample (mean, 162 cells), NVP resistance mutations (K103N and G190A) were found in the latent reservoir in four of 50 (8%) evaluable women.
• Conclusions: Single-dose NVP can establish ARV resistance within the latent reservoir resulting in a potentially lifelong risk of re-emergence of NVP-resistant virus. This emphasises the need for strategies to prevent transmission that do not compromise successful future therapy.
Link 25 June 2009

Predictors of kidney tubular dysfunction in HIV-infected patients treated with tenofovir: a pharmacogenetic study.

Rodríguez-Nóvoa S, Labarga P, Soriano V et al. Clin Infect Dis 2009;48:e108–16. • This study investigated the association between kidney tubular dysfunction due to TDF and polymorphisms in genes encoding drug transporters.
• Kidney tubular dysfunction was higher among patients with genotype CC at position -24 of ABCC2 than among those with genotypes CT and TT (24% [16/68 patients] versus 6% [3/47 patients]; p=0.020). In a multivariate analysis, older age (OR: 1.1; 95% CI: 1.0–1.2; p=0.024), lower body weight (OR: 0.9; 95% CI: 0.8–0.9; p=0.048) and genotype CC at ABCC2 position -24 (OR 5; 95% CI: 1.2–21; p=0.027) were independently associated with kidney tubular dysfunction.
• Conclusions: Homozygosity for the C allele at position -24 of the ABCC2 gene was strongly associated with kidney tubular dysfunction. This polymorphism may help to identify patients at greater risk for developing TDF-associated tubulopathy. These patients should be closely monitored for renal function.
Link 25 June 2009

A randomized trial comparing plasma drug concentrations and efficacies between 2 nonnucleoside reverse-transcriptase inhibitor-based regimens in HIV-infected patients receiving rifampicin: the N2R Study.

Manosuthi W, Sungkanuparph S, Tantanathip P et al. Clin Infect Dis 2009;48:1752–9. • This clinical trial (N2R) in patients with concurrent HIV-1 and TB infection receiving rifampicin compared EFV- and NVP-based ART.
• At weeks 6 and 12, the mean (± SD) concentrations 12 hours after dosing for EFV were 4.27±4.49 and 3.54±3.78 mg/L, respectively, and for NVP were 5.59±3.48 and 5.6±2.65 mg/L, respectively.
• At week 12, 3.1% of EFV patients and 21.3% NVP patients had drug concentrations that were less than the recommended minimum concentrations (OR: 8.396; 95% CI: 1.808–38.993; p=0.002).
• Conclusions. EFV-based ART was less compromised by concomitant use of rifampicin than NVP-based ART in patients with concurrent HIV-1 and TB infection. Low drug exposure and low body weight were important predictive factors for treatment failure.
Link 24 August 2009

High frequency of clinically significant mutations after first-line generic highly active antiretroviral therapy failure: implications for second-line options in resource-limited settings.

Kumarasamy N, Madhavan V, Venkatesh KK et al. Clin Infect Dis 2009;49:306–9. • Continuing failed ART regimens may lead to the accumulation of mutations, potentially limiting options for second-line treatment.
• This study investigated the pattern of drug-resistance mutations among 138 Indian patients who experienced failure of first-line NNRTI-based ART.
• Conclusions: There was a high frequency of drug-resistance mutations in patients who experienced immunological treatment failure. This suggests a need for VL monitoring.
Link 24 August 2009

Telaprevir with peginterferon and ribavirin for chronic HCV genotype 1 infection.

McHutchison JG, Everson GT, Gordon SC et al. N Engl J Med 2009;360:1827–38. • This study compared telaprevir, a PI specific for the HCV non-structural 3/4A serine protease, plus peginterferon alfa-2a and ribavirin with peginterferon alfa-2a and ribavirin in patients with HCV genotype 1 infection.
• Telaprevir was administered for 12 weeks with peginterferon alfa-2a and ribavirin for 12 (T12PR12), 24 (T12PR24) or 48 (T12PR48) weeks. Control patients received peginterferon alfa-2a and ribavirin for 48 weeks.
• The primary endpoint was a sustained virologic response (an undetectable HCV RNA level 24 weeks after the end of therapy).
• The rate of sustained virologic response was 41% in the control group compared with 61% in the T12PR24 group (p=0.02), 67% in the T12PR48 group (p=0.002) and 35% in the T12PR12 group.
• The rate of discontinuation due to adverse events was higher in the three telaprevir-based groups than the control group (21% versus 11%). Rash the most common reason for discontinuation.
• Conclusions: Telaprevir significantly improved the sustained virologic response rates in patients with HCV genotype 1 infection, although the rate of discontinuation due to adverse events as higher.
Link 24 August 2009

Telaprevir and peginterferon with or without ribavirin for chronic HCV infection.

Hézode C, Forestier N, Dusheiko G et al. N Engl J Med 2009;360:1839–50. • This study investigated telaprevir in treatment-naïve patients with chronic HCV genotype 1 infection.
• Patients were randomised to one of four regimens: telaprevir for 12 weeks plus peginterferon alfa-2a and ribavirin for 12 weeks (T12PR12), telaprevir for 12 weeks plus peginterferon alfa-2a and ribavirin for 24 weeks (T12PR24), telaprevir and peginterferon alfa-2a without ribavirin for 12 weeks (T12P12) and peginterferon alfa-2a and ribavirin for 48 weeks (control).
• The primary endpoint was a sustained virologic response (an undetectable HCV RNA level 24 weeks after the end of therapy).
• The rate of sustained virologic response was 46% in the control group compared with 36% in the T12P12 group (p=0.20), 48% in the T12PR12 and T12P12 groups combined (p=0.89), 60% in the T12PR12 group (p=0.12) and 69% in the T12PR24 group (p=0.004).
• Conclusions: Telaprevir for 12 weeks plus peginterferon alfa-2a and ribavirin for 24 weeks had a significantly higher rate of sustained virologic response than standard therapy.
Link 24 August 2009

Tuberculosis treatment and risk of stavudine substitution in first-line antiretroviral therapy.

Westreich DJ, Sanne I, Maskew M et al. Clin Infect Dis 2009;48:1617–23. • This study investigated the effect of TB treatment on stavudine toxicity among patients receiving first-line ART.
• Three exposure categories were considered: ongoing TB treatment at ART initiation, concurrent initiation of TB treatment and ART and TB treatment started after ART initiation. The outcome was single-drug stavudine substitution.
• Patients with ongoing and concurrent TB treatment were at increased risk of stavudine substitution, irrespective of stavudine dosage.
• TB treatment started after ART initiation had no effect on stavudine substitution risk.
• Conclusions: The risk of stavudine substitution was increased among patients who received TB treatment and was especially elevated during the period soon after ART initiation. In settings in which alternative ARVs are available, initiation of stavudine in patients receiving TB treatment may need to be reconsidered.
Link 25 August 2009

Efavirenz dose reduction is safe in patients with high plasma concentrations and may prevent efavirenz discontinuations.

Van Luin M, Gras L, Richter C et al. J Acquir Immune Defic Syndr 2009 Jul 10. [Epub ahead of print] • This study investigated whether EFV dose reduction in patients with high plasma concentrations prevents toxicity-induced EFV discontinuations.
• HIV-infected patients with a high EFV plasma concentration (≥4.0 mg/L) while using EFV 600 mg once daily as part of HAART regimen were selected from the AIDS Therapy Evaluation in The Netherlands cohort study.
• Of 180 patients with high plasma EFV levels, 47 subsequently had the dose reduced from 600 mg to 400 mg once-daily, which resulted in a 41% decrease in the median EFV plasma concentration.
• At week 48, the Kaplan-Meier estimated cumulative incidence of toxicity-induced EFV discontinuations was 11.5% in patients on the standard dose versus 2.3% in patients who had a dose reduction (p=0.066, log-rank test).
• Dose reduction was not associated with loss of virological suppression.
• Conclusions: Dose reduction may prevent toxicity-induced discontinuations in patients with high EFV plasma concentrations without compromising virological efficacy.
Link 16 September 2009

Increased risk of hepatotoxicity in HIV-infected pregnant women receiving antiretroviral therapy independent of nevirapine exposure.

Ouyang et al. AIDS 2009;23:2425–30. • This study investigated whether the association between (NVP) and hepatotoxicity differs according to pregnancy status in HIV-infected women.
• Two outcomes were assessed: any liver enzyme elevation (grade 1–4) and severe liver enzyme elevation (grade 3–4).
• Data on 2050 HIV-infected women taking ART were included: 1229 (60%) were pregnant and 821 (40%) were not.
• Among pregnant women, 174 (14.2%) developed any liver enzyme elevation and 15 (1.2%) developed severe liver enzyme elevation compared with 75 (9.1%) and 5 (0.6%), respectively, of the non-pregnant women.
• In multivariate adjusted models, NVP was not significantly associated with a risk of liver enzyme elevation, regardless of pregnancy status.
• However, pregnancy was associated with an increased risk of any liver enzyme elevation (RR: 4.7; CI: 3.4–6.5) and severe liver enzyme elevation (RR: 3.8; CI: 1.3–11.1).
• The association of pregnancy and liver enzyme elevation was seen, regardless of prior ART and NVP exposure history.
• Conclusions: No significant association between NVP and liver enzyme elevation was observed, regardless of pregnancy status, but pregnancy was significantly associated with increased hepatotoxicity in HIV-infected women.
Link 16 September 2009

Rate of accumulation of thymidine analogue mutations in patients continuing to receive virologically failing regimens containing zidovudine or stavudine: implications for antiretroviral therapy programs in resource-limited settings.

Cozzi-Lepri A, Phillips AN, Martinez-Picado J et al. J Infect Dis 2009;200:687–97. • This study investigated the effect of continuing virologically failing ART in resource-limited settings in terms of the rate of accumulation of thymidine analogue mutations (TAMs).
• The study included patients in EuroSIDA with two genotypic resistance tests ([HIV RNA >500 copies/mL in any measure between tests, the first being performed after the first VF of a TA, which was continued until the second test.
• At the first test, 1 year after VF, a median of three TAMs were detected. Overall, 126 TAMs were accumulated during 548 person-years of follow-up (1/4.3 years; 95%CI: 3.7–5.0 years).
• Greater predicted activity of the TA at t0, TAM profile 2 (versus TAM profile 1) at t0, use of a NNRTI at t0 (versus combined NNRTI and PI), and heterosexual acquisition of HIV (versus homosexual) were associated with a faster rate of TAM accumulation.
• Conclusions: Although the estimated rate of TAM accumulation was lower than anticipated, all possible efforts should be continued to increase the availability of drug options in resource-limited settings.
Link 16 September 2009

Slow accumulation of HIV resistance mutations: implications for resource-limited settings?

Stevens WS. J Infect Dis 2009;200:670–2. • This study investigated the effect of continuing virologically failing ART in resource-limited settings in terms of the rate of accumulation of thymidine analogue mutations (TAMs).
• The study included patients in EuroSIDA with two genotypic resistance tests ([HIV RNA >500 copies/mL in any measure between tests, the first being performed after the first VF of a TA, which was continued until the second test.
• At the first test, 1 year after VF, a median of three TAMs were detected. Overall, 126 TAMs were accumulated during 548 person-years of follow-up (1/4.3 years; 95%CI: 3.7–5.0 years).
• Greater predicted activity of the TA at t0, TAM profile 2 (versus TAM profile 1) at t0, use of a NNRTI at t0 (versus combined NNRTI and PI), and heterosexual acquisition of HIV (versus homosexual) were associated with a faster rate of TAM accumulation.
• Conclusions: Although the estimated rate of TAM accumulation was lower than anticipated, all possible efforts should be continued to increase the availability of drug options in resource-limited settings.
Link 16 September 2009

Safety and efficacy of raltegravir-based versus efavirenz-based combination therapy in treatment-naive patients with HIV-1 infection: a multicentre, double-blind randomised controlled trial.

Lennox JL, Dejesus E, Lazzarin A et al. Lancet 2009 Jul 31 [Epub ahead of print] • This study compared the safety and efficacy of RAL with EFV as part of ART for treatment-naive patients.
• Patients (n=556) were randomised to 400 mg oral RAL twice daily (n=281) or 600 mg oral EFV (282) once daily, in combination with TDF and FTC. Three patients were not treated.
• The primary efficacy endpoint was a viral RNA concentration <50 copies/mL at week 48 in the per-protocol population.
• In the RAL group, 86.1% (n=241 patients) and 81.9% (n=230) in the EFV group patients achieved the primary endpoint (difference 4.2%; 95% CI: –1.9 to 10.3).
• The time to viral suppression was shorter for RAL than EFV (log-rank test p<0.0001).
• Significantly fewer drug-related adverse events occurred with RAL (n=124 [44.1%]) than EFV (n=217 [77.0%]; difference –32.8%; 95% CI: –40.2 to –25.0; p<0.0001).
• Conclusions: RAL-based ART had rapid and potent ARV activity, which was non-inferior to that of EFV at week 48. RAL is a well-tolerated alternative to EFV as part of ART in treatment-naïve patients.
Link 16 September 2009

Raltegravir: a new choice in HIV and new chances for research.

Emery S, Winston A. Lancet 2009 Jul 31 [Epub ahead of print] • This study compared the safety and efficacy of RAL with EFV as part of ART for treatment-naive patients.
• Patients (n=556) were randomised to 400 mg oral RAL twice daily (n=281) or 600 mg oral EFV (282) once daily, in combination with TDF and FTC. Three patients were not treated.
• The primary efficacy endpoint was a viral RNA concentration <50 copies/mL at week 48 in the per-protocol population.
• In the RAL group, 86.1% (n=241 patients) and 81.9% (n=230) in the EFV group patients achieved the primary endpoint (difference 4.2%; 95% CI: –1.9 to 10.3).
• The time to viral suppression was shorter for RAL than EFV (log-rank test p<0.0001).
• Significantly fewer drug-related adverse events occurred with RAL (n=124 [44.1%]) than EFV (n=217 [77.0%]; difference –32.8%; 95% CI: –40.2 to –25.0; p<0.0001).
• Conclusions: RAL-based ART had rapid and potent ARV activity, which was non-inferior to that of EFV at week 48. RAL is a well-tolerated alternative to EFV as part of ART in treatment-naïve patients.
Link 16 November 2009

High rate of virologic suppression with raltegravir plus etravirine and darunavir/ritonavir among treatment-experienced patients infected with multidrug-resistant HIV: results of the ANRS 139 TRIO trial.

Yazdanpanah Y, Fagard C, Descamps D et al. Clin Infect Dis 2009;49:1441–9. • This phase II, non-comparative, multicentre study investigated the safety and efficacy of RAL plus ETV and DRV/r in treatment-experienced patients with multidrug-resistant HIV.
• The primary endpoint was the proportion of patients with plasma HIV RNA levels <50 copies/mL at 24 weeks.
• In addition to the investigational drugs, 90 patients (87%) received optimised background therapy that included NRTIs (86 patients) or ENF (12 patients).
• At weeks 24 and 48, 90% (95% CI: 85–96%) and 86% (95% CI: 80–93%) of patients, respectively, had an HIV RNA level <50 copies/mL. The median CD4 cell count increase was 108 cells/mm3.
• Grade 3/4 adverse events were reported in 15 patients (14.6%). Only one patient discontinued the investigational regimen because of an adverse event.
• Conclusions: The combination of RAL, ETV and DRV/r was well tolerated in treatment-experienced patients infected with multidrug-resistant virus and was associated with a rate of virologic suppression similar to that expected in treatment-naïve patients.
Link 18 December 2009

Long-term evolution and determinants of renal function in HIV-infected patients who began receiving combination antiretroviral therapy in 1997-1999, ANRS CO8 APROCO-COPILOTE.

Leport C et al. Clin Infect Dis 2009;49:1950–4. • This study investigated the long-term evolution and determinants of renal function in HIV+ patients who began receiving combination ART in 1997–1999
• Among 1,121 HIV+ patients (90% caucasian), the glomerular filtration rate increased (+0.72 mL/minute/1.73 m2/month) from treatment initiation to month 16.
• The rate increase was lower among men and those with a low BMI, AIDS, or treatment with IDV, then remained stable up to 7 years.
• Conclusions: Kidney function should be monitored in patients previously exposed to IDV.
Link 02 March 2010

Impact of tenofovir on renal function in HIV-infected, antiretroviral-naive patients.

Horberg M et al. J Acquir Immune Defic Syndr 2010;53:62–9. • This retrospective cohort study compared renal function among ARV-naïve patients starting a TDF-containing (964 patients) or TDF-sparing regimen (683 patients).
• Glomerular filtration rate (GFR), serum creatinine and the development of renal proximal tubular dysfunction were evaluated.
• TDF was associated with a larger relative decline in GFR over 104 weeks (–7.6 mL/min/1.73 m2 versus a TDF-sparing regimen (p< 0.001); the relative difference varied by baseline GFR, with the greatest effect seen in patients with a GFR >80 mL/min/1.73 m2.
• TDF was also associated with a higher rate of proximal tubular dysfunction over time (HR[adjusted]:1.95; p=0.01 at 52 weeks and 5.23; p=0.0004 at 104 weeks) and an increased risk of discontinuation (HR(adjusted): 1.21; p=0.02), particularly as renal function deteriorated.
• Conclusions: TDF was associated with a greater effect on renal function and a higher risk of proximal tubular dysfunction in ARV-naïve patients starting ARV treatment.
Link 02 March 2010

Substitution of nevirapine because of efavirenz toxicity in AIDS clinical trials group A5095.

Schouten JT et al. Clin Infect Dis 2010;50:787–91. • In the AIDS Clinical Trials Group study A5095, 9% of patients who experienced an EFV-related adverse event substituted NVP.
• Most adverse events resolved but 15 patients discontinued NVP.
• Grade 3/4 hepatotoxicity was observed in 14% of patients who substituted NVP versus 6% who continued EFV.
• Conclusion: Substitution of NVP because of EFV toxicity was generally safe and effective.
Link 02 March 2010

Nevirapine/zidovudine/lamivudine has superior immunological and virological responses not reflected in clinical outcomes in a 48-week randomized comparison with abacavir/ zidovudine/lamivudine in HIV-infected Ugandan adults with low CD4 cell counts.

Munderi P et al. HIV Med 2010 Feb 2. • This safety study compared NVP with ABC in ARV-naïve patients with CD4 cell counts <200 cells/mm3 in two Ugandan DART centres.
• Documented WHO stage 4 events were independently reviewed and plasma HIV-1 RNA assayed retrospectively. Exploratory efficacy analyses were ITT.
• The study drug was substituted in 7% of ABC patients vs 11% of NVP patients (p=0.09). At 48 weeks, 62% of ABC patients vs 77% of NVP patients had a VL <50 copies/mL (P<0.001) and mean CD4 cell count increases from baseline were +147 vs +173 cells/mm3, respectively (p=0.006).
• Twenty ABC patients vs 32 NVP patients developed new or recurrent WHO 4 events or died (HR: 0.60; 95% CI: 0.34–1.05; p=0.07) and 48 vs 68 developed new or recurrent WHO 3/4 events or died (HR: 0.67; 95% CI: 0.46–0.96; p=0.03).
• Conclusions: The clear virological/immunological superiority of NVP over ABC was not reflected in clinical outcomes over 48 weeks. The inability of CD4 cell count/VL to predict initial efficacy is unexplained and requires further evaluation.
Link 02 March 2010

Daily aciclovir for HIV-1 disease progression in people dually infected with HIV-1 and herpes simplex virus type 2: a randomised placebo-controlled trial.

Lingappa JR et al. Lancet 2010 Feb 12. • This multicentre study in southern and east Africa investigated the effect of acyclovir on HIV-1 progression in ARV-naïve heterosexuals with dual HSV type 2 and HIV-1 infection and a CD4 cell count ≥200 cells/mm3.
• The effect of aciclovir on HIV-1 disease progression was defined by a primary composite endpoint of first occurrence of CD4 cell counts <200 cells/mm3, ART initiation or non-trauma related death.
• Acyclovir reduced the risk of HIV-1 disease progression by 16% (HR: 0.84; 95% CI: 0.71–0.98; p=0.03). In patients with CD4 cell counts ≥350 cells/mm3, acyclovir delayed the risk of CD4 cell counts falling to <350 cells/mm3 by 19% (HR: 0.81; 95% CI: 0.71–0.93; p=0.002).
• Conclusions: The role of suppression of HSV type 2 in reducing HIV-1 disease progression before starting ART warrants consideration.
Link 02 March 2010

Treating HIV infection with drugs for HSV-2 infection?

Buvé A, Lynen L. Lancet 2010 Feb 12. • This multicentre study in southern and east Africa investigated the effect of acyclovir on HIV-1 progression in ARV-naïve heterosexuals with dual HSV type 2 and HIV-1 infection and a CD4 cell count ≥200 cells/mm3.
• The effect of aciclovir on HIV-1 disease progression was defined by a primary composite endpoint of first occurrence of CD4 cell counts <200 cells/mm3, ART initiation or non-trauma related death.
• Acyclovir reduced the risk of HIV-1 disease progression by 16% (HR: 0.84; 95% CI: 0.71–0.98; p=0.03). In patients with CD4 cell counts ≥350 cells/mm3, acyclovir delayed the risk of CD4 cell counts falling to <350 cells/mm3 by 19% (HR: 0.81; 95% CI: 0.71–0.93; p=0.002).
• Conclusions: The role of suppression of HSV type 2 in reducing HIV-1 disease progression before starting ART warrants consideration.
Link 22 March 2010

Relationship between HIV/highly active antiretroviral therapy (HAART)-associated lipodystrophy syndrome and stavudine-triphosphate intracellular levels in patients with stavudine-based antiretroviral regimens.

Domingo P et al. Infect Dis 2010;50:1033–40. • This study investigated whether there is a link between intracellular levels of d4T and HAART-associated lipodystrophy syndrome (HALS) by measuring intracellular levels of d4T-triphosphate (TP) in peripheral blood mononuclear cells in 17 patients with and 16 patients without HALS.
• The median concentration of d4T-TP was 20.60 femtomoles (fmol)/1 x 106 cells (interquartile range [IQR]: 14.90–26.92) for patients with HALS and 13.85 fmol/1 x 106 cells (IQR: 8.65–20.15) for patients without HALS.
• d4T-TP levels were correlated with cumulative d4T exposure by time and dose. d4T-TP intracellular levels were independently associated with HALS (OR: 1.58; 95% CI: 1.08–2.32).
• Conclusions: Intracellular levels of d4T-TP were strongly associated with the development of HALS.
Link 25 June 2010

Comparison of 2 doses of liposomal amphotericin B and conventional amphotericin B deoxycholate for treatment of AIDS-associated acute cryptococcal meningitis: a randomized, double-blind clinical trial of efficacy and safety.

Hamill RJ et al. Clin Infect Dis 2010;51:225–32. • This study compared the efficacy and safety of liposomal amphotericin B (3 or 6mg/kg/day) with that of conventional amphotericin deoxycholate in patients with AIDS and acute cryptococcal meningitis.
• Efficacy was similar for all three treatments.
• The overall incidence of infusion-related reactions was significantly lower for both liposomal doses compared with conventional amphotericin B (p<0.001).
• The 3 mg/kg/day liposomal amphotericin B dose was associated with significantly less nephrotoxicity than conventional amphotericin B (p=0.004).
• Conclusions: Liposomal amphotericin B provides an equally effective alternative to conventional amphotericin B deoxycholate in patients with AIDS and acute cryptococcal meningitis.
Link 25 June 2010

Antiretroviral regimens in pregnancy and breast-feeding in Botswana.

Shapiro RL et al. N Engl J Med 2010;362:2282–94. • This randomised study investigated the efficacy HAART regimens to prevent mother-to-child transmission of HIV-1.
• Women received ABC/3TC/AZT (NRTI group), LPV/r + AZT/3TC (PI group) or NVP/3TC/AZT (observational group). Infants received single-dose NVP and 4 weeks of AZT.
• The rate of virological suppression to <400 copies/mL was high and did not differ significantly between the three groups at delivery (NRTI 96%, PI 93% and observational 94%) or during breast feeding (NRTI 92%, PI 93% and observational 95%).
• By 6 months of age, 8/709 live-born infants (1.1%) were infected (95% CI: 0.5–2.2): six were infected in utero (four in the NRTI, one in the PI and one in the observational group) and two were infected during breast feeding (in the NRTI group).
• Treatment-limiting adverse events occurred in 2% of women in the NRTI and PI groups and 11% of women in the observational group.
• Conclusions: All regimens resulted in high rates of virological suppression, with an overall mother-to-child transmission rate of 1.1%.
Link 25 June 2010

Maternal or infant antiretroviral drugs to reduce HIV-1 transmission.

Chasela CS et al. N Engl J Med 2010;362:2271–81. • This study investigated the efficacy of a maternal triple-drug ARV regimen or infant NVP prophylaxis for 28 weeks during breast-feeding to reduce post-natal transmission of HIV-1 in Malawi.
• All mothers and infants received perinatal prophylaxis with single-dose NVP and 1 week of AZT plus 3TC.
• Among mother-infant pairs, 5.0% of infants were HIV+ at 2 weeks.
• The estimated risk of HIV-1 transmission at 2–28 weeks was higher in the control group (5.7%) than in either the maternal- (2.9%, p=0.009) or the infant-regimen group (1.7%, p<0.001).
• The estimated risk of infant HIV-1 infection or death at 2–28 weeks was 7.0% in the control group, 4.1% in the maternal- (p=0.02), and 2.6% in the infant-regimen group (p<0.001).
• Conclusions: The use of either a maternal ARV regimen or infant NVP for 28 weeks was effective in reducing HIV-1 transmission during breast feeding.
Link 05 July 2010

Nevirapine-associated early hepatotoxicity: incidence, risk factors, and associated mortality in a primary care ART programme in South Africa.

Chu KM et al. PLoS One 2010;5:e9183. • This study investigated NVP-associated hepatotoxicity among 1,809 HIV+ ARV-naïve adults starting NVP-based therapy.
• The cumulative proportion of early hepatotoxicity was 1–2%, giving an incidence rate at 102 days of 3.6–7.6 per 100 person-years. The median time to hepatotoxicity was 32 days (IQR 28–58 days).
• No association was found between age, gender, baseline CD4 count, concurrent TB infection, prior participation in a programme to prevent mother-to-child-transmission, or baseline weight and early hepatotoxicity.
• Hepatotoxicity was not associated with mortality.
• Conclusions: The cumulative proportion of early hepatotoxicity with NVP-based ART was low in this resource-constrained setting.
Link 13 August 2010

Effectiveness of non-nucleoside reverse-transcriptase inhibitor-based antiretroviral therapy in women previously exposed to a single intrapartum dose of nevirapine: a multi-country, prospective cohort study.

Stringer JSA et al. PLoS Med 2010 Feb 16;7(2):e1000233. • This study investigated whether women with prior exposure to single-dose NVP would have a higher prevalence of failure with an NNRTI-containing regimen during the first 48 weeks of treatment than women without prior exposure.
• Women who died, discontinued NNRTI-containing ART or had a confirmed plasma VL ≥400 copies/mL were designated treatment failures.
• Overall, 114/355 NVP-exposed (32.1%) and 132/523 NVP-unexposed women (25.2%) were treatment failures (6.9% difference in failure rate; 95% CI: 0.8–13.0%).
• Locally weighted regression analysis indicated a clear inverse relationship between VF and exposure interval.
• Conclusions: Prior exposure to single-dose NVP was associated with an increased risk of treatment failure but this was largely confined to women with more recent exposure. Women needing ART within 12 months of NVP treatment should not be prescribed an NNRTI-containing regimen as first-line therapy.
Link