The Role of Prior HBV Infection on the Efficacy of 3TC/DTG as a Maintenance Therapy

Lamivudine/dolutegravir (3TC/DTG) is an effective and well-tolerated antiretroviral regimen for most people with HIV (PWH) who are virologically suppressed; however, specific clinical characteristics, such as prior hepatitis B virus (HBV) exposure or archived resistance-associated mutations (RAMs), may influence the risk of virological failure (VF). We conducted a retrospective, monocentric cohort study to evaluate the incidence and predictors of VF among PWH who switched to 3TC/DTG after achieving virological suppression (HIV-RNA < 50 copies/mL). A total of 188 PWH were included. Over 5082 patient-years of follow-up (PYFU), 8 individuals (4.3%) experienced VF, corresponding to an incidence rate of 1.45 per 1000 PYFU. The cumulative probabilities of VF at 1, 2, 3, 4, and 5 years were 0.6%, 2.7%, 2.7%, 4.2%, and 22.3%, respectively. In exploratory multivariable analyses, anti-HBc positivity was associated with an increased risk of VF (adjusted hazard ratio [aHR] 4.80, 95% CI 1.03-22.43; <i>p</i> = 0.046). After adjustment for age and sex, individuals with anti-HBc positivity who had switched from a tenofovir-containing regimen showed the highest risk of VF compared with anti-HBc-negative individuals without prior tenofovir exposure (aHR 15.06, 95% CI 1.40-161.38; <i>p</i> = 0.025). Given the limited number of virological events, these findings should be interpreted with caution. Nevertheless, they suggest that prior HBV exposure, particularly in the context of tenofovir discontinuation, may represent a clinically relevant factor when considering simplification to 3TC/DTG.