Antiretroviral-specific associations between bone hormonal changes and treatment induced weight gain

Background: Weight gain is common in treatment naïve people with HIV (PWH) initiating antiretroviral therapy (ART). The mechanisms driving this weight gain are unclear. The current study tested the hypothesis that bone-derived hormones are associated with weight gain with ART initiation and that the associations are antiretroviral (ARV) specific. Methods: Plasma samples were obtained from the Advancing Clinical Therapeutics Globally (ACTG) study A5260 s, in which treatment naïve PWH were initiated on tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) plus either atazanavir/ritonavir (ATV/r), darunavir/ritonavir (DRV/r), or raltegravir (RAL). Plasma levels of bone-derived hormones, undercarboxylated osteocalcin (ucOCN), lipocalin-2 (NGAL), and sclerostin and body weight were measured at baseline and 48-weeks after ART initiation. The associations between change in bone-derived hormones and weight with ART initiation were assessed using linear regression models adjusted for age, sex, race, baseline viral load, and CD4 cell count change. Results: Increases in ucOCN and decreases in NGAL were associated with weight change in PWH initiating ART. Sclerostin was not associated with weight change. When assessed as a function of ART, both ucOCN and NGAL were associated with weight for participants initiating RAL-based ART, but not ATV/r or DRV/r. After adjustment, the association between ucOCN and weight was no longer significant, while the association with NGAL remained statistically significant in RAL recipients. Conclusions: This study suggests links between bone-derived hormones and ART induced weight gain in PWH and demonstrates that this relationship is influenced by specific antiretrovirals.