Effectiveness of switching regimen in people living with HIV and persistent low-level viraemia in the modern antiretroviral treatment era.

OBJECTIVES: Persistent low-level viraemia (pLLV) remains a clinical challenge despite antiretroviral therapy (ART). Evidence guiding optimal therapeutic management is still limited, particularly in the modern ART era dominated by second-generation integrase inhibitors. We aimed to evaluate virological outcomes following pLLV based on ART changes. METHODS: Cohort study on adult people living with HIV (PLWH) on ART with ≥1 pLLV episode since 2014. pLLV was defined as ≥2 consecutive viral loads 50-199 copies/mL ≥30 days apart, preceded by a viral load <50 copies/mL. The primary outcome was virological suppression (viral load <50 copies). Follow-up accrued from the first viral load 50-199 copies/mL (baseline) to virological suppression, virological failure (≥2 consecutive viral loads ≥200 or ≥1 viral load ≥1000 copies/mL), a second ART modification among those who had already switched once during the follow-up or the last available viral load. Predictors of time to virological suppression were evaluated using Cox regression, treating ART switch as a time-dependent variable. RESULTS: Among 6794 PLWH in care, 451 (6.6%) experienced pLLV. After a median follow-up of 9.0 months, 81.2% achieved virological suppression and 3.5% developed virological failure. ART was switched in 176 (39.0%) individuals. ART switching was associated with a shorter time to virological suppression (adjusted hazard ratio = 2.1, 95% confidence interval = 1.7-2.7, p < 0.001), even in individuals on regimens with a higher barrier to resistance. Higher baseline viraemia was inversely associated with the hazard of virological suppression. Genotypic resistance data during pLLV were limited; however, resistance-associated mutations might have been potentially selected in 22 (4.9%) PLWH. CONCLUSIONS: In the current ART era, switching ART during pLLV may shorten the time to virological suppression, even among individuals receiving regimens with a higher barrier to resistance. Prompt and careful evaluation of treatment optimization is reasonable in this setting.