CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

Mean maximum threshold for phosphate reabsorption (TmPO 4 /GFR) according to tenofovir (TDF) exposure, stratified by age Conclusions: In HIV-positive men, reduced phosphate reabsorption was common. Similar to observations reported in the general population, TmPO 4 /GFR declined with age but was not significantly associated with TDF exposure, increased bone resorption, or lower BMD. Our results suggest that in patients stable on antiretroviral therapy, TmPO 4 /GFR may not be useful in identifying patients at increased risk of bone loss. 769LB Less Bone Loss With a Maraviroc Regimen in HIV-Infected Treatment-Naïve Subjects Babafemi Taiwo 1 ; Ellen Chan 2 ; Carl Fichtenbaum 3 ; Heather Ribaudo 2 ; AtheTsibris 4 ; Karin Klingman 5 ; Joseph J. Eron 6 ; Baiba Berzins 1 ;ToddT. Brown 7 ACTG A5303 StudyTeam 1 Northwestern University, Feinberg School of Medicine, Chicago, IL, US; 2 Statistical and Data Analysis Center, Harvard School of Public Health, Boston, MA, US; 3 University of Cincinnati, Cincinnati, OH, US; 4 Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, US; 5 National Institutes of Health, Bethesda, MD, US; 6 University of North Carolina at Chapel Hill, Chapel Hill, NC, US; 7 Johns Hopkins University School of Medicine, Baltimore, MD, US 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 comparisons Results: 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 log 10 c/mL and CD4 count was 390 cells/mm 3 . 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/mm 3 , 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-tolerated Conclusions: 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 2:30 pm– 4:00 pm Bone Disease: Mechanisms of Bone Loss and Fracture Risk 770 Association of Adipokines With Bone Mineral Density in HIV+ and HIV- Women Anjali Sharma 1 ;Yifei Ma 2 ; Rebecca Scherzer 2 ; Amber L.Wheeler 2 ; Mardge Cohen 3 ; Deborah Gustafson 4 ; MichaelTYin 5 ; Phyllis C.Tien 2 1 Albert Einstein College of Medicine, Bronx, NY, US; 2 University of California San Francisco, San Francisco, CA, US; 3 John H. Stroger Jr. Hospital of Cook County, Chicago, IL, US; 4 State University of New York Downstate Medical Center, Brooklyn, NY, US; 5 College of Physicians and Surgeons, Columbia University, New York, NY, US Background: HIV infection is associated with low bone mineral density (BMD) and alterations in adipose-derived hormones (adipokines) such as leptin and adiponectin. Studies in the general population suggest that adipokines may be important mediators of the relationship between fat and bone, however their relationship to BMD in HIV+ populations is unknown. Methods: BMD of the lumbar spine (LS), total hip (TH), and femoral neck (FN) were measured by dual X-ray absorptiometry (DXA) at baseline and over 5 years in 440 participants (318 HIV+, 122 HIV-) enrolled in the Metabolic Substudy of the Women’s Interagency HIV Study. Serum leptin and adiponectin were assayed on stored sera. Multivariable linear mixed models were used to assess the effects of adipokines and HIV status on BMD over 5 years, adjusting for demographic, behavioral, and body composition and metabolic factors, and menopausal status. Models restricted to HIV+ women also adjusted for CD4, HIV RNA, and HAART use. Results: Compared with HIV- women, HIV+ women were older (mean 44 vs. 37 years) and more likely to be post-menopausal (26% vs. 3%). HIV+ women had lower BMI (27kg/m 2 vs. 30kg/m 2 ), and lower leptin (18ng/mL vs. 28ng/mL) but higher adiponectin (9.4 m g/mL vs. 6.4 m g/mL) levels at the baseline visit. In unadjusted analysis, HIV+ women had lower TUESDAY, FEBRUARY 24, 2015 Session P-Q3 Poster Session Poster Hall

Poster Abstracts

471

CROI 2015