Peripheral and Central Fat Changes in Subjects Randomized to Abacavir-Lamivudine or Tenofovir-Emtricitabine With Atazanavir-Ritonavir or Efavirenz: ACTG Study A5224s

• Published in: Clinical infectious diseases Vol. 53; no. 2; pp. 185 - 196
• Main Authors: McComsey, Grace A., Kitch, Douglas, Sax, Paul E., Tebas, Pablo, Tierney, Camlin, Jahed, Nasreen C., Myers, Laurie, Melbourne, Kathleen, Ha, Belinda, Daar, Eric S.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 15.07.2011
• Subjects: Adipose tissues; Adult; Anti-HIV Agents - administration & dosage; Anti-HIV Agents - adverse effects; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiretroviral drugs; Antiretroviral Therapy, Highly Active - adverse effects; Antiretroviral Therapy, Highly Active - methods; Antiviral agents; Biological and medical sciences; Body fat; Body Fat Distribution; Body mass index; Clinical trials; Drug therapy; Fats; Female; HIV; HIV 1; HIV Infections - drug therapy; HIV Infections - virology; HIV-1 - isolation & purification; HIV-Associated Lipodystrophy Syndrome - chemically induced; HIV/AIDS; Human immunodeficiency virus; Human immunodeficiency virus 1; Humans; Infectious diseases; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Random allocation; Registered nurses; RNA; Visceral fat; Purine nucleoside; Antiretroviral agent; Benzoxazine derivatives; RNA-directed DNA polymerase; Acetylenic compound; Ritonavir; Non nucleoside compound; Nucleotide analog; Efavirenz; Tenofovir; Reverse transcriptase inhibitor; Nucleoside analog; Antiviral; Pyrimidine nucleoside; Emtricitabine; Human; Purine nucleotide; Acyclic nucleotide; Atazanavir; Enzyme; Transferases; Enzyme inhibitor; Lamivudine; Organic phosphonate; Infection; Allosteric inhibitor; Peptidases; Nucleotidyltransferases; Dideoxynucleoside; Abacavir; Fat; Hydrolases; Protease inhibitor
• ISSN: 1058-4838; 1537-6591
• DOI: 10.1093/cid/cir324

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 log₁₀ 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 cm², 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.