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

Lamivudine/dolutegravir (3TC/DTG) is effective and safe for most people with HIV infection (PWH) who are virologically suppressed, but specific individual’s characteristics, such as previous detection of archived resistance-associated mutations (RAMs) to 3TC and prior HBV infection, could represent a risk for virological failure (VF). We conducted a retrospective monocentric cohort study to assess rates and predictors of treatment discontinuation (TD) and VF in PWH switched to 3TC/DTG after reaching virological suppression (HIV-RNA<50 cp/mL). Overall, 188 PWH were included. Over 5145 patient-years follow-up (PYFU), 16 (8.5%) PWH experienced TD (2.87 per 1000 PYFU), whereas over 5082 PYFU, 8 (4.3%) experienced VF (1.45 per 1000 PYFU). Probabilities of TD and VF were 1.3%, 2.8%, 7.5%, 12.9%, 34.5% and 0.6%, 2.7%, 2.7%, 4.2%, 22.3% after 1, 2, 3, 4 and 5 years respectively. Independent predictors of VF were a detectable baseline HIV-RNA of 20-49 copies/ml (versus<20 copies/ml, aHR 9.11, 95 % CI 1.05-79.40; p= 0.046), and a higher GSS-score for 3TC (per 10 points more, aHR 1.57, 95 % CI 1.07-2.29; p= 0.023), with a borderline significance for anti-HBcAg positive serostatus (versus negative, aHR 8.88, 95 % CI 0.89-88.45; p= 0.062). After adjustment for age and gender, those with anti-HBcAg positivity who switched from a tenofovir-containing regimen had the highest risk of VF (versus negative anti-HBcAg and no prior tenofovir use, aHR 15.06, 95% CI 1.40-161.38; p-value= 0.025).