Peripheral and central fat changes in subjects randomized to abacavir-lamivudine or tenofovir-emtricitabine with atazanavir-ritonavir or efavirenz: ACTG Study A5224s.

TitlePeripheral and central fat changes in subjects randomized to abacavir-lamivudine or tenofovir-emtricitabine with atazanavir-ritonavir or efavirenz: ACTG Study A5224s.
Publication TypeJournal Article
Year of Publication2011
AuthorsMcComsey GA, Kitch D, Sax PE, Tebas P, Tierney C, Jahed NC, Myers L, Melbourne K, Ha B, Daar ES
JournalClin Infect Dis
Volume53
Issue2
Pagination185-96
Date Published2011 Jul 15
ISSN1537-6591
KeywordsAdult, Anti-HIV Agents, Antiretroviral Therapy, Highly Active, Body Fat Distribution, Female, HIV Infections, HIV-1, HIV-Associated Lipodystrophy Syndrome, Humans, Male, Middle Aged
Abstract

BACKGROUND: We compare the effect of 4 different antiretroviral regimens on limb and visceral fat.

METHODS: A5224s was a substudy of A5202, a trial of human immunodeficiency virus type 1 (HIV-1)-infected, treatment-naive subjects randomized to blinded abacavir-lamivudine (ABC-3TC) or tenofovir DF-emtricitabine (TDF-FTC) with open-label efavirenz (EFV) or atazanavir-ritonavir (ATV-r). The primary endpoint was the presence of lipoatrophy (≥ 10% loss of limb fat) at week 96 by intent-to-treat (ITT) analysis. Secondary endpoints included changes in limb and visceral fat. Statistical tests included linear regression, binomial, two-sample t test, and Fisher's exact test.

RESULTS: A5224s enrolled 269 subjects; 85% were male, and 47% were white non-Hispanic. The subjects had a median baseline HIV-1 RNA level of 4.6 log(10) copies/mL, a median age of 38 years, a median CD4+ cell count of 233 cells/μL, median limb fat of 7.4 kg, median visceral adipose tissue (VAT) of 84.1 cm(2), and VAT: total adipose tissue (TAT) ratio of 0.31. At week 96, estimated prevalence of lipoatrophy (upper 95% confidence interval [CI]) was 18% (25%) for ABC-3TC and 15% (22%) for TDF-FTC (P = .70); this was not significantly less than the hypothesized 15% for both (P ≥ .55 for both). The secondary as-treated (AT) analysis showed similar results. At week 96, the estimated mean percentage change from baseline in VAT was higher for the ATV-r group than for the EFV group (26.6% vs 12.4%; P = .090 in ITT analysis and 30.0% vs 14.5%; P = .10 in AT analysis); however, the percentage change in VAT:TAT was similar by ITT and AT analysis (P ≥ .60 for both). Results were similar for absolute changes in VAT and VAT:TAT.

CONCLUSIONS: ABC-3TC- and TDF-FTC-based regimens increased limb and visceral fat at week 96, with a similar prevalence of lipoatrophy. Compared to the EFV group, subjects assigned to ATV-r had a trend towards higher mean percentage increase in VAT.

CLINICAL TRIALS REGISTRATION: NCT00118898.

DOI10.1093/cid/cir324
Alternate JournalClin. Infect. Dis.
PubMed ID21690627
PubMed Central IDPMC3165963
Grant ListAI0450008 / AI / NIAID NIH HHS / United States
AI065348 / AI / NIAID NIH HHS / United States
AI069424 / AI / NIAID NIH HHS / United States
AI069472 / AI / NIAID NIH HHS / United States
AI38855 / AI / NIAID NIH HHS / United States
AI69501 / AI / NIAID NIH HHS / United States
P30 AI050410 / AI / NIAID NIH HHS / United States
U01 AI068636 / AI / NIAID NIH HHS / United States
U01 AI68634 / AI / NIAID NIH HHS / United States
UL1 RR033176 / RR / NCRR NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States