Weight and lean body mass change with antiretroviral initiation and impact on bone mineral density

Abstract

Objective: To compare the effect that initiating different antiretroviral therapy (ART) regimens has on weight, BMI, and lean body mass (LBM) and explore how changes in body composition are associated with bone mineral density (BMD).

Methods: A5224s was a sub-study of A5202, a prospective trial of 1857 ART-naive participants randomized to blinded abacavir-lamivudine (ABC/3TC) or tenofovir DF-emtricitabine (TDF/FTC) with open-label efavirenz (EFV) or atazanavir-ritonavir (ATV/r). All participants underwent dual-energy absorptiometry (DXA) and abdominal computed tomography for body composition. Analyses used two-sample t-tests and linear regression.

Results: A5224s included 269 participants: 85% men, 47% white non-Hispanic, median age 38 years, HIV-1 RNA 4.6 log10 copies/ml, and CD4 cell count 233 cells/μl. Overall, significant gains occurred in weight, BMI, and LBM at 96 weeks post-randomization (all P<0.001). Assignment to ATV/r (vs. EFV) resulted in significantly greater weight (mean difference 3.35 kg) and BMI gain (0.88 kg/m; both P=0.02), but not LBM (0.67 kg; P=0.15), whereas ABC/3TC and TDF/FTC were not significantly different (P≥0.10). In multivariable analysis, only lower baseline CD4 cell count and higher HIV-1 RNA were associated with greater increase in weight, BMI, or LBM. In multivariable analyses, increased LBM was associated with an increased hip BMD.

Conclusion: ABC/3TC vs. TDF/FTC did not differ in change in weight, BMI, or LBM; ATV/r vs. EFV resulted in greater weight and BMI gain but not LBM. A positive association between increased LBM and increased hip BMD should be further investigated through prospective interventional studies to verify the impact of increased LBM on hip BMD.

Trial registration: ClinicalTrials.gov NCT00118898.

Figures

Figure 1

Absolute changes in total weight, body mass index, and lean body mass by treatment arms. Mean and 95% confidence intervals are represented by symbols and error bars; P value from comparison between arms at 96 weeks; TDF/FTC, tenofovir-emtricitabine; ABC/3TC, abacavir-lamivudine; EFV, efavirenz; ATV/r, atazanavir-ritonavir. A. Changes in total weight between the nucleoside reverse transcriptase inhibitor (NRTI) and non-nucleoside reverse transcriptase inhibitor/protease inhibitor (NNRTI/PI) components. B. Changes in body mass index between NRTI and NNRTI/PI components. C. Changes in lean body mass between NRTI and NNRTI/PI components.