Background: Although lipoatrophy is uncommon with current antiretroviral therapy (ART), fat accumulation continues to occur, and its association with protease inhibitors (PIs) has been questioned. The effect of integrase inhibitors vs. PIs on body composition has not been established.
Methods: We compared the percentage change in lean mass (by DXA), peripheral fat (limb fat by DXA and subcutaneous abdominal fat (SAT) by CT scan of abdomen), and central fat (trunk fat by DXA and visceral abdominal fat (VAT) by CT) over 96 weeks in HIV-infected treatment-naive participants randomized to open labeled tenofovir disoproxil fumarate-emtricitabine (TDF/FTC) plus atazanavir-ritonavir (ATV/r), darunavir-ritonavir (DRV/r), or raltegravir (RAL) in ACTG 5260s, a substudy of A5257. DXA and CT measurements were standardized and centrally read. Linear regression, adjusting for the stratification factors of baseline cardiometabolic risk and HIV-1 RNA, was used to compare the 96-week percentage change in fat and lean mass in the two PI arms (ATV/r vs DRV/r) and, if not different, the PI arms were combined and compared to RAL arm. Associations between baseline biomarkers and changes in body composition were assessed with linear regression models adjusting for baseline age, BMI, HIV-RNA, CD4 count, sex and race/ethnicity. Within arm changes were assessed with signed-rank tests. All analyses were intent-to-treat.
Results: 328 participants were randomized; 90% were male and 44% white, non-Hispanic; median age was 36 years, HIV-1 RNA load 4.55 log10 copies/mL, and CD4 count 349 cells/μL. At week 96, the median percentage increases in limb fat, SAT, VAT, trunk fat, and lean mass were statistically significant in all arms (8.2%, 10.9%, 13.9%, 11.4%, 1.3%; p<0.001). Changes for all fat outcomes were not different between the PI arms (p≥0.36), however greater gains in lean mass with ATV/r vs. DRV/r were detected (3.8% vs. 2.3%; p=0.05). There were no significant differences between the RAL arm and combined PI arm in any fat or lean mass endpoints (p≥0.36). While lower baseline leptin and higher RNA levels were associated with greater gains in peripheral and central fat, higher baseline IL-6 was only associated with greater gains in peripheral fat.
Conclusions: In ART-naïve subjects initiating ART with TDF/FTC, RAL led to similar increases in lean mass, and central and peripheral fat as compared to ATV/r and DRV/r. We saw no evidence to suggest that the PIs were associated with greater increases in central fat than RAL