Viral suppression after failure of PI-based ART among adolescents and youths with and without drug resistance mutations: a longitudinal analysis in Tanzania

Abstract

BACKGROUND: People living with HIV (PLHIV) who fail first-line ART have a higher risk of failing subsequent ART. We examined viral suppression (VS) among adolescents and youths (AY) failing PI ART in Tanzania. METHODS: We conducted a retrospective study nested within a national third-line cohort of PLHIV. We analysed data of 147 AY (aged 10-24 years) with failure of PI-based ART between 2020 and 2022 who were followed for 12 months to assess for VS. Descriptive statistics were summarized by demographics and clinical characteristics, and we used logistic regression to assess factors associated with virological failure (VF) and drug resistance mutations (DRMs). RESULTS: More than 40% of 147 participants had HIV subtype A, 52% (76/147) harboured major PI DRMs and 35% had NRTI mutations. A PI regimen at ART initiation was associated with a major PI DRM adjusted relative risk (aRR) of 1.66 (95% CI: 1.13-2.44; P = 0.010). Among participants with major PI DRMs, 12.2% had intermediate to high levels of resistance to lopinavir and atazanavir, and 2.1% to darunavir, respectively. V82A was the most frequent PI DRM; NRTI mutations included thymidine analogue mutations and absent K65R. VS occurred in 65% of AY who had PI DRMs compared with 45% of those without DRMs; this difference was not statistically significant. CONCLUSIONS: More than half of AY who had PI DRMs had a higher proportion of early VS (65%) compared with those without DRMs (45%). Optimal viral load monitoring, adherence intensification and routine drug resistance testing are key strategies to improve VS.