Background: Bone mineral density (BMD) decreases by 2-6% in the first 2 years of antiretroviral therapy (ART). The decline is 1-2% greater with tenofovir (TDF) than other nucleos(t)ide reverse transcriptase inhibitors (NRTI). The effects of maraviroc (MVC) on BMD are unknown. We investigated a novel regimen containing MVC dosed 150mg once daily (QD).
Methods: A 48 wk double-blind, placebo-controlled trial was conducted at US ACTG and ATN sites. Subjects were HIV-1-infected, ART-naïve with viral load (VL) >1000 c/mL and R5 tropism on Trofile®. Exclusion criteria included any major NRTI or darunavir (DRV) mutation; active hepatitis B; and CrCl <50 mL/min. Subjects were randomized 1:1 to MVC 150mg or TDF 300mg QD, stratified by VL< and ≥100,000 c/mL and age < and ≥30 yrs. All subjects received DRV 800mg, ritonavir (RTV) 100mg, and emtricitabine (FTC) 200mg QD. Dual-energy x-ray absorptiometry (DXA) scanning was done at baseline and wk48. Primary endpoint was percentage change in total hip BMD from baseline to wk48. Secondary endpoints included percentage change in lumbar spine BMD, time to virologic failure (VF), and change in CD4 count. VF was defined as confirmed VL >1000 c/mL at or after wk16 and before wk24, or confirmed VL > 200 c/mL at or after wk24. All analyses were as-treated. P-values were not adjusted for multiple comparisonsResults: We enrolled 262 subjects. The analysis population (N=259; 130 MVC, 129 TDF) was 91% male; median age 33yrs, 45%White, 30%Black, 22%Hispanic. At baseline, median VL was 4.5 log10 c/mL and CD4 count was 390 cells/mm3. Decline in hip BMD (as-treated N=115 for MVC, 109 for TDF) from baseline to wk48 was less with MVC: median (Q1, Q3) change in BMD of -1.51% (-2.93%, -0.11%) vs -2.40% (-4.30%, -1.32%) for TDF (Wilcoxon p<0.001). Median lumbar spine BMD decline was also less with MVC (-0.88% vs -2.35%, p<0.001). Virologic outcomes in both arms were good; VF probabilities by wk24 were 4% for MVC vs. 2% for TDF, and 6% vs. 5% by wk48 (log-rank p=0.57). VL ≤50 c/mL was 85%MVC vs. 93%TDF at wk24 (p=0.06) and 94% in each arm at wk48 (p=0.89). CD4 change from baseline to wk48 was greater with MVC; median of +234 vs. +188 cells/mm3, p=0.036. At wk48, CrCl was >90 mL/min in 90%MVC, 91%TDF. All results were similar with ITT analyses. Both regimens were well-toleratedConclusions: Initiating ART with QD MVC, FTC and DRV/RTV resulted in less bone loss compared to TDF-based therapy with no apparent difference in virologic efficacy. MVC may be an option to attenuate early bone-loss