New Publications in HIV : Archive

15 May 2009

Stable frequency of HIV-1 transmitted drug resistance in patients at the time of primary infection over 1996-2006 in France.

Chaix ML, Descamps D, Wirden M et al. AIDS 2009;23:717–24. • This study reports the transmission of drug-resistant HIV-1 among 1,446 French patients diagnosed at the time of primary infection and included from 1996–2006 and the proportion of chronically infected treated patients in the French Hospital Database on HIV (FHDH).
• The proportion of transmitted resistant HIV was 10.9%. There was an increase in the transmission of NNRTI resistance from 0.6% in 1996–1998 to 4.4% in 1999 (p=0.034) but no change in NRTI or PI resistance.
• In the FHDH, the proportion of patients receiving combination ART increased from 27.7% in 1996 to 81.4% in 2006 and the proportion of VL <500 copies/ml in treated patients increased from 17.0% in 1996 to 85.3% in 2006.
• Conclusion: The frequency of acquired resistant virus was stable over time, >5% for NRTI and NNRTI resistance. This stability may be due to the increasing number of treated patients with virological success.
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

Virological monitoring and resistance to first-line highly active antiretroviral therapy in adults infected with HIV-1 treated under WHO guidelines: a systematic review and meta-analysis.

Gupta RK, Hill A, Sawyer AW, Cozzi-Lepri A et al. Lancet Infect Dis. 2009;9:409–17. • This meta-analysis assessed the effect of variable monitoring on the emergence of resistance after therapy with commonly used drug combinations by reviewing studies reporting resistance in patients infected with HIV and a CD4 count of <200 cells/μL treated with two NRTIs and an NNRTI.
• Resistance at VF to NNRTIs at 48 weeks was 88.3% (95% CI: 82.2–92.9) in infrequently monitored patients, compared with 61.0% (95% CI: 48.9–72.2) in frequently monitored patients (p<0.001).
• Lamivudine resistance was 80.5% (95% CI: 72.9–86.8) and 40.3% (95% CI: 29.1–52.2) in infrequently and frequently monitored patients, respectively (p<0.001).
• The prevalence of at least one thymidine analogue mutation was 27.8% (95% CI: 21.2–35.2) and 12.1% (95% CI: 5.9–21.4), respectively (p<0.001).
• Genotypic resistance at 48 weeks to lamivudine, NRTIs and NNRTIs was substantially higher in patients who were less frequently monitored.
• Conclusion: There is a need for cheap point-of-care VL tests to identify early viral failures and limit the emergence of resistance.
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 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 22 April 2010

The impact of transmitted drug-resistance on treatment selection and outcome of first-line highly active antiretroviral therapy (HAART).

Bansi L et al. J Acquir Immune Defic Syndr 2010;53:633–9. • This study investigated how resistance testing influences the outcome of first-line HAART in routine practice in the UK.
• The prevalence of transmitted drug resistance and the genotypic sensitivity score (GSS) of first-line HAART regimens were determined using data from the UK Collaborative HIV Cohort (CHIC) Study.
• Amongst patients tested from 1999–2006, 116/1175 (10%) had ≥1 resistance mutation; 64 patients (5.4%) had ≥1 mutation associated with resistance to drugs in the initial HAART regimen and 54 (4.6%) showed a GSS <3.
• Factors independently associated with a GSS <3 were starting HAART in 1999–2001 vs 2004–2006 (OR: 2.63; 95% CI: 1.19–5.83) and use of PI/r-based vs NNRTI-based regimens (OR: 1.97; 95% CI: 1.06–3.64).
• A GSS >3 was independently associated with virological suppression (HR for GSS <3: 0.60; 95% CI: 0.41–0.87).
• Conclusions: Most patients starting HAART after undergoing resistance testing received regimens with a GSS ≥3. A low GSS predicted poor virological suppression and the association persisted after adjusting for PI/r use.
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