New Publications in HIV

13 August 2010

Use of generic antiretroviral agents and cost savings in PEPFAR treatment programs.

Holmes CB et al. JAMA 2010;304:313–20. • This study evaluated the uptake of generic ARVs and changes over time in ARV use and costs among PEPFAR (US President's Emergency Plan for AIDS Relief) -supported programmes in Guyana, Haiti, Vietnam and 13 countries in Africa.
• ARV expenditures increased from $116.8 million (2005) to $202.2 million (2008) and procurement increased from 6.2 million to 22.1 million monthly packs.
• The proportion spent on generic ARVs increased from 9.17% (95% CI: 9.17–9.18%) in 2005 to 76.41% (95% CI: 76.41–76.42%) in 2008 (p<0.001) and the proportion of generic packs procured increased from 14.8% (95% CI: 14.79–1.84%) in 2005 to 89.33% (95% CI: 89.32–89.34%) in 2008 (p<0.001).
• Conclusions: Among PEPFAR-supported programmes in 16 countries, the availability of generic ARVs was associated with increased ARV procurement and substantial estimated cost savings.
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 13 August 2010

Early versus standard antiretroviral therapy for HIV-infected adults in Haiti.

Severe P et al. N Engl J Med 2010;363:257–65. • This randomized, open-label study compared early with standard initiation of ART in HIV+ adults in Haiti who had a confirmed CD4 cell count 200–350 cells/mm3 at baseline and no history of an AIDS illness.
• Early treatment consisted of AZT, 3TC and EFV therapy within 2 weeks of enrollment. Standard treatment used the same regimen when the CD4 cell count fell to ≤200 cells/mm3 or when clinical AIDS developed. The primary endpoint was survival.
• A total of 408 patients were enrolled in each group. There were 23 deaths in the standard- versus six in the early-treatment group (HR: 4.0; 95% CI: 1.6–9.8; p=0.001).
• Conclusions: Early initiation of ART decreased the rates of death and incident TB. Access to ART should be expanded to include all HIV+ adults with a CD4 cell count <350 cells/mm3, including those in resource-limited regions.
Link 13 August 2010

Antiretroviral treatment of adult HIV infection: 2010 recommendations of the International AIDS Society-USA panel.

Thompson MA, JAMA 2010;304:321–33. • Updated recommendations of the International AIDS Society-USA guidelines for the management of HIV-infected adults, using ARVs and laboratory monitoring tools available in the developed world.
• Conclusions: Patient readiness for treatment should be confirmed before initiation of ART. Treatment is recommended for asymptomatic patients with a CD4 cell count ≤500 cells/mm3, for all symptomatic patients and those with specific conditions and comorbidities.
• Treatment should be considered for asymptomatic patients with a CD4 cell count >500 cells/mm3.
• Components of the initial and subsequent regimens must be individualized, particularly in the context of concurrent conditions.
• Patients receiving ART should be regularly monitored.
• Treatment failure should be detected and managed early, with the goal of therapy, even in heavily pre-treated patients, being HIV-1 RNA suppression below commercially available assay quantification limits.
Link 29 July 2010

Test and treat DC: forecasting the impact of a comprehensive HIV strategy in Washington DC.

Walensky RP et al. Clin Infect Dis 2010;51:392–400. • This study used a mathematical model of HIV case detection and treatment to evaluate combinations of HIV-screening and ART-initiation strategies.
• Current practice was defined as no regular screening program and ART at CD4 counts ≤350 cells/mm3 and test and treat was defined as annual screening and administration of ART at diagnosis.
• Outcomes included life expectancy of HIV-infected persons and changes in the population time with transmissible HIV RNA levels.
• The projected life expectancies, from an initial mean age of 41 years, are 23.9, 25.0 and 25.6 years for current practice, test and treat and test and treat with optimised ART, respectively.
• Compared with current practice, test and treat and test and treat with optimized ART would lead to a 14.7% and 27.3% reduction, respectively, in the time spent with transmissible HIV RNA level in the next 5 years.
• Conclusions: An expanded HIV test and treat programme in Washington DC would increase the life expectancy of HIV+ patients but would only have a modest impact on HIV transmission over the next 5 years that is unlikely to halt the HIV epidemic.
Link 29 July 2010

Rate of CD4+ cell count increase over periods of viral load suppression: relationship with the number of previous virological failures.

Trotta MP et al. Clin Infect Dis 2010;51:456–64. • This study analysed patients with ≥1 episode of viral suppression after starting first-line ART (n=3,537) from the ICONA Foundation study.
• The percentage of patients with an increase in CD4 cell count >300 cells/mm3 and the rate of CD4 cell count increase per year were estimated.
• The median time to reach a CD4 cell count increase >300 cells/mm3 was significantly associated with the number of failed regimens: 34, 41, 51 and 45 months in patients without evidence of previous virological failure and 1, 2 or ≥3 previous virological failures, respectively (p<0.001). The annual estimated increases in CD4 cell count were 36, 28, 31 and 26 cells/mm3, respectively.
• Conclusions: Patients with ≥1 virological failure took a longer time to reach a CD4 cell count >300 cell/mm3 and had a slower annual increase than those without virological failure.
• First-line ART should be optimised to provide the best chance of achieving an effective CD4 cell response.
Link 29 July 2010

Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1.

Wu X et al. Science. 2010 Jul 8. • In this study, antigenically resurfaced glycoproteins specific for the structurally conserved site of CD4 receptor binding were developed.
• These probes were used to identify sera with neutralising antibodies to the CD4-binding site and to isolate individual B-cells from the HIV-1-infected donor.
• Three monoclonal antibodies, including a pair of somatic variants, which neutralised >90% of circulating HIV-1 isolates, were identified.
• Conclusions: Exceptionally broad HIV-1 neutralisation can be achieved with individual antibodies targeted to the functionally conserved CD4-binding site of gp120, providing an important insight for the future design of an HIV-1 vaccine.
Link 05 July 2010

Effect of treating co-infections on HIV-1 viral load: a systematic review

Modjarrad K, Vermund SH. Lancet Infect Dis, 2010;10:455–63 • This systematic review assessed the effect of treating key co-infections on plasma HIV-1-RNA levels in resource-constrained countries.
• Standardised mean plasma VL decreased after the treatment of co-infecting pathogens in all 18 studies.
• Twelve of 14 studies with variance data reported significant differences in HIV VL before and after treatment.
• Conclusions: Although many of the VL reductions were ≤1.0 log10 copies/mL, even small changes in plasma HIV-RNA concentrations can slow HIV progression and could translate into population-level benefits in lowering the risk of HIV transmission.
Link 05 July 2010

Risk of resistance to highly active antiretroviral therapy among HIV-positive injecting drug users: a meta-analysis.

Werb D et al. Lancet Infect Dis, 2010;10:464–9. • This meta-analysis analysed 12 studies comparing ARV resistance rates in HIV+ current or previous injecting drug users (IDUs) with HIV+ non-IDUs.
• The risk of developing ARV resistance was not significantly different between IDUs and non-IDUs (OR: 1•04; 95% CI: 0•74–1•45; p=0•84).
• Rates of loss to follow-up and VF were similar in IDUs and non-IDUs.
• Conclusions: The evidence does not support the common practice of withholding ART from HIV+ IDUs on the basis of an increased risk of ARV resistance.
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