Mitochondrial DNA haplogroups and weight gain following switch to INSTI-Based ART.

BACKGROUND Integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART) has been associated with excess weight gain in some adults, which may be influenced by genetic factors. We assessed mitochondrial DNA (mtDNA) haplogroups and weight gain following switch to INSTI-based ART. METHODS All AIDS Clinical Trials Group A5001 and A5322 participants with mtDNA genotyping who switched to INSTI were included. mtDNA haplogroups were derived from prior genotyping algorithms. Race/ethnicity-stratified piecewise linear mixed effects models assessed the relationship between mtDNA haplogroup and weight change slope differences before and after switch to INSTI. RESULTS 291 adults switched to INSTI: 78% male, 50% non-Hispanic White, 28% non-Hispanic Black, and 22% Hispanic. The most common European haplogroups were H (n = 66 [45%]) and UK (32 [22%]). Non-H European haplogroups had significant increase in weight slope after the switch. This difference was greatest among non-H clade UK on INSTI-based regimens that included tenofovir alafenamide (TAF) (3.67 [95% CI 1.12, 6.21] kg/year; p = 0.005). Although small sample size limited analyses among non-Hispanic Black and Hispanic persons, similarly significant weight gain was seen among the most common African haplogroup, L3 (n = 29 [39%]; slope difference 4.93 [1.54, 8.32] kg/year, p = 0.005), after switching to TAF-containing INSTI-based ART. CONCLUSIONS Those in European mtDNA haplogroup clade UK and African haplogroup L3 had significantly greater weight gain after switching to INSTI-based ART, especially those receiving TAF. Additional studies in large and diverse populations are needed to clarify mechanisms and host risk factors for weight gain after switching to INSTI-based ART, with and without TAF.