Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV‐1 resistance mutation

Abstract

The aim of the study was to investigate whether lamivudine (3TC) or emtricitabine (FTC) use following detection of M184V/I is associated with better virological outcomes. MethodsWe identified people with viruses harbouring the M184V/I mutation in UK multicentre data sets who had treatment change/initiation within 1 year. We analysed outcomes of viral suppression (< 200 HIV-1 RNA copies/mL) and appearance of new major drug resistance mutations (DRMs) using Cox and Poisson models, with stratification by new drug regimen (excluding 3TC/FTC) and Bayesian implementation, and estimated the effect of 3TC/FTC adjusted for individual and viral characteristics. ResultsWe included 2597 people with the M184V/I resistance mutation, of whom 665 (25.6%) were on 3TC and 458 (17.6%) on FTC. We found a negative adjusted association between 3TC/FTC use and viral suppression [hazard ratio (HR) 0.84; 95% credibility interval (CrI) 0.71-0.98]. On subgroup analysis of individual drugs, there was no evidence of an association with viral suppression for 3TC (n = 184; HR 0.94; 95% CrI 0.73-1.15) or FTC (n = 454; HR 0.99; 95% CrI 0.80-1.19) amongst those on tenofovir-containing regimens, but we estimated a reduced rate of viral suppression for people on 3TC amongst those without tenofovir use (n = 481; HR 0.71; 95% CrI 0.54-0.90). We found no association between 3TC/FTC and detection of any new DRM (overall HR 0.92; 95% CrI 0.64-1.18), but found inconclusive evidence of a lower incidence rate of new DRMs (overall incidence rate ratio 0.69; 95% CrI 0.34-1.11). ConclusionsWe did not find evidence that 3TC or FTC use is associated with an increase in viral suppression, but it may reduce the appearance of additional DRMs in people with M184V/I. 3TC was associated with reduced viral suppression amongst people on regimens without tenofovir. HIV Medicine (2020), 21, 309--321 3TC/FTC use after detection of M184V/I 311 9 Eron JJ, Benoit SL, Jemsek J et al. Treatment with lamivudine, zidovudine, or both in HIV-positive patients with 200 to 500 CD4+ cells per cubic millimeter. N Engl J Med 1995; 333 (25): 1662-1669.

Dolutegravir response in antiretroviral therapy naïve and experienced patients with M184V/I: Impact in low-and middle-income settings

“…Reasons behind viral suppression on DTG/NRTIs regimens in patients carrying M184V/I Firstly, 3TC or FTC are constituents of DTG-based regimens and continual use of either 3TC or FTC in presence of M184V has been shown to encourage viral suppression and also reduce emergence of additional DRMs (Campbell et al, 2005;Stirrup et al, 2020). M184V has been associated with significantly lower plasma viral RNA levels in AVANT 2 and AVANT 3 studies (Maguire et al, 2000).…”