Body Composition Changes in Children Living With HIV Initiated on Dolutegravir or Protease Inhibitors in the CHAPAS-4 Trial
Natukunda E., Szubert AJ., Bwakura-Dangarembizi M., Mulenga V., Doerholt K., Lugemwa A., Byaruhanga S., Nambi E., Ndebele W., Nyathi M., Gibb DM., Ndeezi G., Walker AS., Musoke P., Musiime V.
Background: Few studies have compared body composition changes in children living with HIV receiving integrase inhibitors or boosted protease inhibitors. Methods: Children switching to second-line antiretroviral therapy were randomized to dolutegravir (DTG), darunavir/ritonavir (DRV/r), atazanavir/ritonavir (ATV/r) or lopinavir/ritonavir (LPV/r), and to tenofovir alafenamide (TAF) or standard of care (abacavir or zidovudine) using a factorial design. Body composition was measured using bioelectric impedance analysis over 96 weeks. Associations between baseline characteristics and changes in fat mass, fat-free mass, muscle mass and body fat percentage were estimated using robust regression with multivariable fractional polynomial selection (exit P = 0.05). Results: Eight hundred forty-one participants were included in the analysis. Females compared with males had greater fat accrual (+4.66% body fat, +1.32 kg fat mass; both P < 0.001). Compared with LPV/r, ATV/r and DTG exposures were associated with higher fat-free mass [+0.85 kg (95% confidence interval: 0.43–1.27) and +0.79 kg (0.37–1.21) respectively] and muscle mass [+0.82 kg (0.41–1.23) and +0.82 kg (0.42–1.22), respectively] (all P < 0.001). TAF and DRV/r exposures were associated with higher fat mass [+0.32 kg (0.12–0.52) P = 0.002; +0.33 kg (0.04–0.61) P = 0.025, respectively]. Prior nevirapine exposure was also associated with greater fat accrual [+0.36 kg (0.13–0.58) vs. efavirenz, P = 0.002]. Baseline CD4 and viral load, time on first-line antiretroviral therapy, and site were also associated with composition changes. Conclusions: DTG and ATV/r were associated with greater gains in fat-free mass and muscle mass than LPV/r, while DRV/r, TAF and prior nevirapine exposure were associated with fat mass accrual. Fat gain may initially reflect return to health but sustained increases may have metabolic implications. These findings suggest the need to monitor fat compartments with long-term exposure.