Body Composition Changes After Initiation of Raltegravir or Protease Inhibitors: ACTG A5260s

Abstract

Background: Fat gain after antiretroviral therapy (ART) occurs, and its association with protease inhibitors (PIs) is unclear.

Methods: Peripheral and central fat depots and lean mass were measured using standardized and centrally read abdominal CT scans and whole-body dual-energy absorptiometry scans over a 96-week period in human immunodeficiency virus (HIV)-infected treatment-naive participants. The patients were randomized to tenofovir-emtricitabine (TDF/FTC) plus atazanavir-ritonavir (ATV/r), darunavir-ritonavir (DRV/r), or raltegravir (RAL) in ACTG A5260s, a substudy of A5257. Within arm changes were assessed with signed-rank tests. The 96-week percentage changes in fat and lean mass in the 2 PI arms were not different, thus the PI arms were combined and compared to the RAL arm. Associations between baseline biomarkers and changes in body composition were assessed. All analyses used linear regression models.

Results: 328 patients were randomized (90% male, 44% white non-Hispanic). The median age was 36 years, HIV-1 RNA 4.6 log10 copies/mL, and CD4 349 cells/μL. Overall, at week 96, increases in limb fat (13.4%), subcutaneous (19.9%) and visceral abdominal fat (25.8%), trunk fat (18%), and lean mass (1.8%) were apparent (P < .001 for changes within each arm). Changes for all fat and lean outcomes were not different between the PI arms or between the RAL and the combined PI arms. Higher baseline HIV-1 RNA levels were associated with greater gains in peripheral and central fat.

Conclusions: In treatment-naive participants initiating ART with TDF/FTC, no differences in lean mass and regional fat were found with RAL when compared with ATV/r or DRV/r over 96 weeks.

Clinical trials registration: NCT00811954 and NCT00851799.

Keywords: body composition; limb fat; lipodystrophy; lipoatrophy; visceral fat.

© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Figures

Figure 1.

Subject disposition. Abbreviations: ART, antiretroviral therapy; ITT, intent-to-treat; NRTI, nucleoside reverse transcriptase inhibitor; VF, virologic failure.

Figure 2.

Changes in body composition parameters in peripheral fat depots: (A) limb fat measured by dual-energy absorptiometry (DXA) scan and (B) subcutaneous adipose tissue measured by computed tomography (CT) scan of abdomen. Changes in body composition parameters in central fat depots: (C) trunk fat measured by DXA scan and (D) visceral adipose tissues measured by CT scan of abdomen. *, ATV/r vs DRV/r and +, PI/r vs RAL. Abbreviations: ATV/r, atazanavir-ritonavir; DRV/r, darunavir-ritonavir; PI, protease inhibitor; RAL, raltegravir; SAT, subcutaneous adipose tissue; VAT, visceral adipose tissue.

Figure 3.

Effect of baseline human immunodeficiency virus type 1 (HIV-1) RNA levels on changes in body composition. (A) A low viral load stratum (HIV-1 RNA <100 000 copies/mL at screening) and (B) a high viral load stratum (HIV-1 RNA ≥100 000 copies/mL at screening). Abbreviations: ATV/r, atazanavir-ritonavir; DRV/r, darunavir-ritonavir; RAL, raltegravir; SAT, subcutaneous adipose tissue; VAT, visceral adipose tissue.