Randomized clinical trials have shown greater weight gain with INSTI regimens vs other classes of antiretrovirals. Why do some patients gain weight on INSTI and others do not? Are there synergies with other ARV agents and INSTI? We examine HIV patients (pts) in US clinical care switching to INSTIs and compare those with gain ≥5% body weight vs loss or gain <5% after 12 months (mo) on INSTIs.
A retrospective evaluation of 38000 HIV pts with EMR records selected 2384 virally suppressed pts per protocol. Subgroup analysis was conducted in 387 subjects: pts ≥18 years, switched to INSTI regimens in Jan 2015-Jun 2018 for ≥12 mo, with ≥6 mo history, viral suppression and weights at baseline [BSL] and 12 mo (±2 mo). Univariate analyses [UV] were conducted via chi-square and t-test. Multivariate analysis [MV] with a binary outcome of gain ≥5% at 12 mo was conducted using log binomial model; variables significant in UV and demographics were considered; final model included continuous variables age, BSL weight and categorical BSL AST <30 vs ≥30, use of prior protease inhibitors [PI] and prior non-nucleoside reverse transcriptase Inhibitors [NNRTI].
Of 387 pts switched to INSTIs, 103 (27%) gained ≥5% weight, 140 (36%) lost weight or had 0% change, 144 (37%) gained <5%. In comparison to other study pts, those who gained ≥5% had significantly lower BSL weight, BMI, AST (but not ALT; alcohol abuse by ICD-10 observed in <4%), lower use of prior PI, and higher use of prior NNRTI. There were no statistically significant differences by NRTI backbone and specific INSTIs between those who gained ≥5% vs those who did not. In MV, pts were less likely to gain ≥5% if they had BSL AST≥30 (relative risk [RR]=0.51 [CI 0.31-0.84], p=0.009) or higher BSL weight (RR=0.99 [CI 0.98-1.00], p=0.034).
Of 387 pts switching to INSTIs, over 1/3 lost or maintained weight, over 1/3 experienced weight gain <5%, while remaining 27% experienced gain ≥5% after 12 mo on therapy. UV indicated ≥5% gain was associated with prior regimen components and BSL factors of which only BSL weight and AST remained significant in MV. Future research questions include clinical significance of weight gain thresholds that have implications for morbidity, as well as heterogeneity of responses to ARV agents.