Background: Lamivudine (3TC) and emtricitabine (FTC) are considered interchangeable in recommended combination antiretroviral therapies (cART) including tenofovir (TDF) with a non-nucleoside reverse transcriptase inhibitor (NNRTI) or boosted protease inhibitor (PI). The evidence for equivalent efficacy of 3TC and FTC in cART is inconsistent and data from randomized clinical trials that directly compare FTC and 3TC are lacking. The purpose of this study was to evaluate the virological responses to 3TC and FTC in combination with TDF and efavirenz (EFV), nevirapine (NVP) or boosted PI in a nationwide cohort.
Methods: Observational cohort study on the AIDS Therapy Evaluation in the Netherlands (ATHENA) nationwide HIV cohort. Included were ART naive HIV-1 infected adults who initiated 3TC or FTC with TDF and either EFV or NVP or boosted PI between 2002 and 2012. Week 48 and week 240 virological failure to 3TC and FTC containing regimens were compared by multivariable adjusted logistic regression in on-treatment analysis. Time to 2 consecutive HIV-1 RNA <400 c/mL and time to virological failure after HIV-1 RNA <400 c/mL were compared by Cox proportional hazard models. Sensitivity analyses included intent to treat (ITT) analysis and propensity score adjusted models.
Results: During the 10 year study period, 6031 ART naive HIV1 infected adults initiated 3TC or FTC with TDF and either EFV (N=3878), NVP (N=862) or boosted PI (N=1291). Week 48 virological failure rates on 3TC compared to FTC were 10.8% and 3.6% with EFV (adjusted odds ratio (aOR):1.78, 95% confidence interval (95%CI):1.11-2.84), 27.0% and 11.0% with NVP (aOR: 2.09, 95%CI:1.25-3.52) and 5.3% and 4.7% with boosted PI (aOR: 1.44, 95%CI:0.51-4.03). Analysis by ITT and propensity score adjusted models gave similar results. The adjusted hazard-ratio on virological failure at week 240 using 3TC instead of FTC was 2.35 (95%CI:1.61-3.42) with EFV, 2.01 (95%CI:1.36-2.98) with NVP and 1.21 (95%CI:0.58-2.52) with boosted PI. The time to virological suppression <400 c/mL within 48 weeks and the time to virological failure after HIV-1 RNA <400 c/mL were not significantly influenced (P>0.05) by including either 3TC or FTC in EFV, NVP or boosted PI containing regimens.
Conclusions: The use of FTC as part of NNRTI containing regimens was associated with better virological responses. These findings are relevant for settings with extensive 3TC use and for including generic 3TC in cART.