Less Bone Loss With Maraviroc- Versus Tenofovir-Containing Antiretroviral Therapy in the AIDS Clinical Trials Group A5303 Study

Abstract

Background: There is a need to prevent or minimize bone loss associated with antiretroviral treatment (ART) initiation. We compared maraviroc (MVC)- to tenofovir disoproxil fumarate (TDF)-containing ART.

Methods: This was a double-blind, placebo-controlled trial. ART-naive subjects with human immunodeficiency virus type 1 RNA load (viral load [VL]) >1000 copies/mL and R5 tropism were randomized to MVC 150 mg or TDF 300 mg once daily (1:1), stratified by VL <100 000 or ≥100 000 copies/mL and age <30 or ≥30 years. All subjects received darunavir 800 mg, ritonavir 100 mg, and emtricitabine 200 mg daily. Dual-energy X-ray absorptiometry scanning was done at baseline and week 48. The primary endpoint was percentage change in total hip bone mineral density (BMD) from baseline to week 48 in the as-treated population.

Results: We enrolled 262 subjects. A total of 259 subjects (130 MVC, 129 TDF) contributed to the analyses (91% male; median age, 33 years; 45% white, 30% black, 22% Hispanic). Baseline median VL was 4.5 log10 copies/mL and CD4 count was 390 cells/µL. The decline in hip BMD (n = 115 for MVC, n = 109 for TDF) at week 48 was less with MVC (median [Q1, Q3] of -1.51% [-2.93%, -0.11%] vs -2.40% [-4.30%, -1.32%] for TDF (P < .001). Lumbar spine BMD decline was also less with MVC (median -0.88% vs -2.35%; P < .001). Similar proportions of subjects in both arms achieved VL ≤50 copies/mL in as-treated and ITT analyses.

Conclusions: MVC was associated with less bone loss at the hip and lumbar spine compared with TDF. MVC may be an option to attenuate ART-associated bone loss.

Clinical trials registration: NCT01400412.

Keywords: bone; darunavir; maraviroc; tenofovir.

© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Figures

Figure 1.

Consolidated Standards of Reporting Trials (CONSORT) diagram. Abbreviations: BMD, bone mineral density; DRV/r, darunavir/ritonavir; DXA, dual-energy X-ray absorptiometry; FTC, emtricitabine; IVDU, intravenous drug user; MVC, maraviroc; TDF, tenofovir disoproxil fumarate.

Figure 2.

Percentage of change in bone mineral density from baseline to week 48 among all participants (A), nonblack participants (B), and non-Hispanic black participants (C). The line inside the box indicates the median value. The lower and upper edges of the box indicate the first and third quartiles (the 25th and 75th percentiles). The lower and upper whiskers are the first and third quintiles ±1.5 times interquartile range. Stratified Wilcoxon rank-sum tests were used to test for differences between the 2 treatment groups, stratified by age (<30 vs ≥30 years). Abbreviations: MVC, maraviroc; TDF, tenofovir disoproxil fumarate.

Figure 3.

Adjusted treatment effects on the percentage of change in hip (A) and spine (B) bone mineral density (BMD) from baseline to week 48 with 95% confidence intervals (CIs). Following initial model diagnostics, 2 extreme outlying and influential data points were excluded: an extreme decrease (−32.1%) in the maraviroc (MVC) group and extreme increase (+26.6%) in the tenofovir disoproxil fumarate (TDF) group. Estimates from simple linear regression analyses are (1) unadjusted, (2) stratified by age (<30 y, ≥30 y) and baseline human immunodeficiency virus type 1 (HIV-1) RNA (<100 000, ≥100 000 copies/mL), (3) adjusted for baseline BMD at the specific site, (4) adjusted for race (nonblack vs non-Hispanic black), and (5) adjusted by race. Models 3–5 are also stratified by age and baseline HIV-1 RNA level; models 4 and 5 also adjust for baseline BMD.