New Publications in HIV

02 March 2010

Timing of Initiation of Antiretroviral Drugs during Tuberculosis Therapy.

Abdool Karim SS et al. N Engl J Med. 2010;362:697–706. • This open-label study conducted in South Africa investigated the optimal timing for starting ART in relation to tuberculosis treatment.
• Patients with tuberculosis and HIV infection were randomised to start ART either during (integrated: two groups) or after the completion of (sequential: one group) standard tuberculosis therapy. The primary end point was death from any cause.
• There was a reduction in the death rate with integrated therapy (5.4 deaths per 100 person-years), vs sequential therapy (12.1 per 100 person-years), a relative risk reduction of 56% (HR: 0.44; 95% CI: 0.25–0.79; p=0.003).
• Conclusions: The initiation of ART during tuberculosis therapy significantly improved survival.
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 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

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

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

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 27 January 2010

Incidence and risk factors for chronic elevation of alanine aminotransferase levels in HIV-infected persons without hepatitis B or C virus co-infection.

Kovari H et al. Clin Infect Dis 2010;50:502–11 • This study investigated the incidence of and risk factors for chronic elevation of alanine aminotransferase (ALT) levels in 2,365 patients participating in the Swiss HIV Cohort Study without HBV or HCV infection.
• Chronic elevated ALT levels developed in 385 patients (16%), with an incidence of 3.9 cases per 100 person-years (95% CI: 3.5–4.3).
• Chronic elevated ALT levels were associated with an HIV RNA level of >100,000 copies/mL (incidence rate ratio [IRR]: 2.23; 95% CI: 1.45–3.43), increased BMI (BMI 25–29.9 IRR: 1.56; 95% CI: 1.24–1.96; BMI 30 IRR: 1.70; 95% CI: 1.16–2.51), severe alcohol use (IRR: 1.83; 95% CI: 1.19–2.80), exposure to stavudine (IRR per year exposure: 1.12; 95% CI: 1.07–1.17) and zidovudine (IRR per year exposure: 1.04; 95% CI: 1.00–1.08]). Black ethnicity was inversely correlated (IRR: 0.52; 95% CI: 0.33–0.82).
• Treatment outcome and mortality did not differ between groups with and groups without elevated ALT levels.
• Conclusions: Chronic elevated ALT levels had an incidence of 3.9 cases per 100 person-years among patients without HBV or HCV co-infection and were associated with high HIV RNA levels, increased BMI, severe alcohol use and prolonged stavudine and zidovudine exposure. Long-term follow-up is needed to assess whether chronic elevation of ALT levels will result in increased morbidity or mortality.
Link 27 January 2010

Switch to a raltegravir-based regimen versus continuation of a lopinavir-ritonavir-based regimen in stable HIV-infected patients with suppressed viraemia (SWITCHMRK 1 and 2): two multicentre, double-blind, randomised controlled trials.

Eron JJ et al. Lancet. 2010 Jan 12. • These studies compared substitution of RAL for LPV/r with continuation of LPV/r in HIV+ patients with stable viral suppression on LPV/r-based treatment.
• The primary endpoints were the mean percentage change in serum lipid concentrations from baseline to week 12; the proportion of patients with a vRNA concentration <50 copies/mL at week 24, with a prespecified non-inferiority margin of –12% for each study; and the frequency of adverse events up to 24 weeks.
• The percentage changes in lipid concentrations from baseline to week 12 were significantly greater (p<0.0001) with RAL versus LPV/r in each study.
• At week 24, 84.4% (95% CI: 80.2–88.1) of patients in the RAL group had a vRNA concentration <50 copies/mL versus 90.6% (95% CI: 87.1–93.5) of patients in the LPV/r group (treatment difference –6.2%; 95% CI : –11.2 to –1.3).
• There was no difference in the frequency of adverse events.
• The studies were terminated at week 24 because of lower than expected virological efficacy of RAL compared with LPV/r.
• Conclusion: Although switching to RAL was associated with greater reductions in serum lipid concentrations than continuation of LPV/r, RAL was not as effective as LPV/r.
Link 27 January 2010

HIV-associated resources on the internet.

Armstrong WS, del Rio C. Top HIV Med 2009;17:151–62. • This review summarises high-quality HIV-related websites, including sites that provide access to HIV-related guidelines, conferences with web content, images, case studies, and clinical and scientific databases.
• It also summarises HIV-related reference and journals sites, patient information/advocacy sites and those for professional societies.
Link 27 January 2010

Evolutionary dynamics of complex networks of HIV drug-resistant strains: the case of San Francisco.

Smith RJ et al. Science 2010 Jan 14. • This study used a biologically complex multi-strain network model, which was designed using insights into the evolution and transmission dynamics of ARV resistance, to trace the evolutionary history of ARV resistance in San Francisco and predict future dynamics.
• Using classification and regression trees, the key immunological, virological and treatment factors that increase ARV resistance were identified.
• The model showed that 60% of the ARV-resistant strains currently circulating in San Francisco could cause self-sustaining epidemics, as each infected individual can cause an average of more than one new resistant infection.
• Conclusion: A new wave of ARV-resistant strains that pose a significant threat to global public health is possibly emerging.
Link