Time to First-Line Antiretroviral Therapy Failure and Its Predictors among People Living with HIV in Tanzania

Abstract

Abstract Introduction Sustaining long-term viral suppression among people living with HIV (PLHIV) remains a major public health challenge in sub-Saharan Africa, despite widespread access to antiretroviral therapy (ART). Evidence on time to first-line ART failure and its predictors at a national scale remains limited, particularly for dolutegravir (DTG)-based regimens. We aimed to estimate the time to first-line ART failure and identify associated predictors among PLHIV in Tanzania using national programmatic data. Methods We conducted a retrospective cohort study using routinely collected data from the National Care and Treatment Clinic database (CTC-2) in Tanzania. The analysis included PLHIV aged ≥11 years who initiated first-line ART between January 2017 and December 2021 and had at least six months of follow-up. Time to first-line ART failure was defined as the duration from ART initiation to the first documented virological failure (viral load ≥1,000 copies/mL). Kaplan-Meier methods were used to estimate failure-free survival, and Cox proportional hazards models were used to identify predictors of failure. Non-proportional hazards for DTG-based regimens were addressed using an extended Cox model with a time-varying coefficient. Results The final analytic cohort comprised 36,764 individuals and 789 first-line treatment failure events. Median follow-up time varied across regimen groups. Failure-free survival differed significantly by regimen anchor (log-rank p<0.001). In multivariable Cox models, age and gender were significantly associated with treatment failure. DTG-based regimens demonstrated a time-varying effect: compared with non-DTG regimens, DTG was associated with a substantially lower hazard of failure early after initiation, with the protective effect attenuating over time. Estimated hazard ratios for DTG versus non-DTG regimens were 0.37, 0.67, and 1.22 at 6, 12, and 24 months of follow-up, respectively. Conclusions In this large national cohort, the risk of first-line ART failure varied by regimen and patient characteristics. DTG-based regimens showed strong early protection against failure, but this effect diminished over time, highlighting the importance of continued virological monitoring after ART initiation. Time-to-event analyses using routine programmatic data provide important evidence for optimizing ART delivery and informing HIV programme decisions in Tanzania and similar settings.