Abstract
ObjectivesThe 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.
Highlights
There has been a history of continuing 3TC/FTC in antiretroviral therapy (ART) regimens for some people living with HIV (PLHIV) with M184V/I because of the potential benefits of maintaining this mutation [5,6] linked to impaired viral fitness and the finding that 3TC seems to retain some antiviral effect even in the presence of the M184V mutation [7]
Through the analysis of UK HIV cohort data, we aimed to investigate whether 3TC/FTC use demonstrates any association with viral suppression or the occurrence of additional major drug resistance mutations (DRMs) following the detection of the M184V/I mutation
The prevalence of the M184V/I DRM was assessed in relation to calendar time stratified by whether PLHIV were recorded as ART-na€ıve or ART-experienced
Summary
One study found that boosted protease inhibitor (bPI) plus 3TC dual maintenance therapy for virally suppressed PLHIV with M184V at prior failure demonstrated an acceptably low failure rate at 48 weeks (3.0%), whereas bPI monotherapy did not (failure rate 24.8%) [8]. This result reflects early ART trials that found zidovudine plus 3TC to be substantially more effective than zidovudine monotherapy [9,10], despite the fact that high-level resistance to 3TC develops rapidly without full viral suppression. This result reflects early ART trials that found zidovudine plus 3TC to be substantially more effective than zidovudine monotherapy [9,10], despite the fact that high-level resistance to 3TC develops rapidly without full viral suppression. 3TC monotherapy is associated with better short-term outcomes than complete treatment interruption amongst PLHIV with M184V [11]
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