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Body Composition Changes in Children Living With HIV Initiated on Dolutegravir or Protease Inhibitors in the CHAPAS-4
Eva Natukunda1, Alex J Szubert2, Mutsa Bwakura-Dangarembizi3
1From the Department of Paediatrics, Joint Clinical Research Centre, Kampala, Uganda.
Insights
Integrase inhibitors dolutegravir (DTG) and atazanavir/ritonavir (ATV/r) increased fat-free and muscle mass in children with HIV. Other treatments like darunavir/ritonavir (DRV/r) and tenofovir alafenamide (TAF) were linked to fat mass gain.
Area of Science:
- Pediatric HIV Research
- Antiretroviral Therapy
- Body Composition Analysis
Background:
- Limited comparative data exists on body composition changes in children with HIV on integrase inhibitors versus boosted protease inhibitors.
- Understanding these differences is crucial for optimizing long-term health outcomes in pediatric HIV management.
Purpose of the Study:
- To compare body composition changes in children living with HIV randomized to different second-line antiretroviral therapies.
- To investigate the association between specific antiretroviral drugs and changes in fat mass, fat-free mass, muscle mass, and body fat percentage.
Main Methods:
- A randomized factorial design trial involving children switching to second-line antiretroviral therapy.
- Participants were assigned to dolutegravir (DTG), darunavir/ritonavir (DRV/r), atazanavir/ritonavir (ATV/r), or lopinavir/ritonavir (LPV/r), and tenofovir alafenamide (TAF) or standard of care.
- Body composition was assessed using bioelectric impedance analysis over 96 weeks, with statistical analysis using robust regression.
Main Results:
- Eight hundred forty-one children were analyzed; females showed greater fat accrual than males.
- Dolutegravir (DTG) and atazanavir/ritonavir (ATV/r) were associated with significantly higher fat-free mass and muscle mass compared to lopinavir/ritonavir (LPV/r).
- Darunavir/ritonavir (DRV/r), tenofovir alafenamide (TAF), and prior nevirapine exposure were linked to increased fat mass accrual.
Conclusions:
- Dolutegravir (DTG) and atazanavir/ritonavir (ATV/r) promote favorable gains in fat-free and muscle mass in children with HIV.
- Darunavir/ritonavir (DRV/r), TAF, and prior nevirapine exposure are associated with fat mass accumulation, which may have long-term metabolic implications.
- Long-term monitoring of body composition, particularly fat compartments, is recommended for children receiving these antiretroviral therapies.
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.
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