How do ARTs affect body composition in children living with HIV?

In children living with HIV, treatment with dolutegravir and atazanavir/ritonavir (ATV/r) appear to yield greater gains in fat-free mass and muscle mass compared with lopinavir/ritonavir (LPV/r), a study has shown. By contrast, darunavir/ritonavir (DRV/r), tenofovir alafenamide (TAF), and prior exposure to nevirapine are associated with gains in fat mass.

A total of 841 children with HIV were included in the analysis. Females had greater fat accrual than males (4.66 percent body fat, 1.32 kg fat mass; p<0.001 for both).

Exposures to dolutegravir and ATV/r significantly correlated with higher fat-free mass (0.85 kg, 95 percent confidence interval [CI], 0.43‒1.27 and 0.79 kg, 95 percent CI, 0.37‒1.21, respectively) and muscle mass (0.82 kg, 95 percent CI, 0.41‒1.23 and 0.82 kg, 95 percent CI, 0.42‒1.22, respectively; p<0.001 for all) compared with LPV/r.

On the other hand, TAF and DRV/r exposures resulted in higher fat mass (0.32 kg, 95 percent CI, 0.12‒0.52; p=0.002 and 0.33 kg, 95 percent CI, 0.04‒0.61; p=0.025, respectively). Likewise, prior exposure to nevirapine correlated with greater fat accrual (0.36 kg, 95 percent CI, 0.13‒0.58; p=0.002) compared with efavirenz.

Furthermore, baseline CD4 and viral load, time on first-line antiretroviral therapy (ART), and site were all significantly associated with changes in body composition.

“Fat gain may initially reflect return to health, but sustained increases may have metabolic implications,” the investigators said. “These findings suggest the need to monitor fat compartments with long-term exposure.”

In this study, children switching to second-line ART were randomized to receive dolutegravir, DRV/r, ATV/r, or LPV/r and to TAF or standard of care (abacavir or zidovudine) using a factorial design. Bioelectric impedance analysis was used to measure body composition over 96 weeks.

The investigators examined the associations between baseline characteristics and changes in fat mass, fat-free mass, muscle mass, and body fat percentage using robust regression with multivariable fractional polynomial selection.