Abstract
IntroductionThere is conflicting evidence and practice regarding the use of the non-nucleoside reverse transcriptase inhibitors (NNRTI) efavirenz (EFV) and nevirapine (NVP) in first-line antiretroviral therapy (ART).MethodsWe systematically reviewed virological outcomes in HIV-1 infected, treatment-naive patients on regimens containing EFV versus NVP from randomised trials and observational cohort studies. Data sources include PubMed, Embase, the Cochrane Central Register of Controlled Trials and conference proceedings of the International AIDS Society, Conference on Retroviruses and Opportunistic Infections, between 1996 to May 2013. Relative risks (RR) and 95% confidence intervals were synthesized using random-effects meta-analysis. Heterogeneity was assessed using the I2 statistic, and subgroup analyses performed to assess the potential influence of study design, duration of follow up, location, and tuberculosis treatment. Sensitivity analyses explored the potential influence of different dosages of NVP and different viral load thresholds.ResultsOf 5011 citations retrieved, 38 reports of studies comprising 114 391 patients were included for review. EFV was significantly less likely than NVP to lead to virologic failure in both trials (RR 0.85 [0.73–0.99] I2 = 0%) and observational studies (RR 0.65 [0.59–0.71] I2 = 54%). EFV was more likely to achieve virologic success than NVP, though marginally significant, in both randomised controlled trials (RR 1.04 [1.00–1.08] I2 = 0%) and observational studies (RR 1.06 [1.00–1.12] I2 = 68%).ConclusionEFV-based first line ART is significantly less likely to lead to virologic failure compared to NVP-based ART. This finding supports the use of EFV as the preferred NNRTI in first-line treatment regimen for HIV treatment, particularly in resource limited settings.
Highlights
There is conflicting evidence and practice regarding the use of the non-nucleoside reverse transcriptase inhibitors (NNRTI) efavirenz (EFV) and nevirapine (NVP) in first-line antiretroviral therapy (ART)
The US Department of Health and Human Services [2] and the International AIDS Society US guidelines [3] recommend a preference for EFV over NVP for first-line therapy
World Health Organisation (WHO) has recommended that EFV should be considered as the preferred first-line NNRTI [4]
Summary
There is conflicting evidence and practice regarding the use of the non-nucleoside reverse transcriptase inhibitors (NNRTI) efavirenz (EFV) and nevirapine (NVP) in first-line antiretroviral therapy (ART). According to the 2010 World Health Organisation (WHO) HIV treatment guidelines [1], the choice of non-nucleoside reverse transcriptase inhibitor (NNRTI) for first-line antiretroviral therapy (ART) for HIV-1 infected adults is either efavirenz (EFV) or nevirapine (NVP), in combination with either zidovudine (AZT) or tenofovir (TDF) and lamivudine (3TC) or emtricitabine (FTC). A previous Cochrane review concluded that there was no difference in efficacy between the two drugs but found a higher risk of acquired resistance for patients on NVP [5] This finding was dominated by the large 2NN Study comparing NVP and EFV regimens that found no difference in efficacy between the two drugs [6]. A more recent review comparing the use of these drugs with TDF-containing regimens concluded that EFV had superior virological efficacy [7]
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