CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

was 2.53% (0.22%, 5.31%) and T-score change was 0.19 (0.02, 0.42) (all p<0.001). At total hip, BMD change at W96 was 2.39% (0.72%, 4.18%) and T-score change was 0.14 (0.04, 0.24) (all p<0.001). Of the 86 with BL osteoporosis and W96 BMD data, 23% no longer met criteria for osteoporosis at W96. Of 214 with low BMD, 24% and 15% had a clinically significant BMD increase at the spine and total hip, respectively. In multivariable analysis, BL factors associated with clinically significant BMD increase at W96 were higher fraction excretion of phosphate (FEPO4 ≥ 10%) for the hip and higher BMI (≥30 kg/m2) and procollagen type 1 N-terminal propeptide (P1NP >1.85 log10 ng/mL) levels for spine. Conclusion: HIV-infected individuals with clinically significant low BMD on a TDF-based regimen who switched to E/C/F/TAF experience a ~2.5% BMD increase over 96 weeks and a reversion from osteoporosis in approximately 1/4 of patients. Baseline urinary phosphate wasting and high bone turnover may identify TDF-treated HIV-infected patients with low BMD who may benefit the most from a switch to TAF. 684 ANTIRETROVIRAL BONE LOSS IS DURABLY SUPPRESSED BY A DOSE OF ZOLEDRONIC ACID Igho Ofotokun , Kehmia Titanji, Aswani Vunnava, Antonina Foster, Anandi N. Sheth, Cecile D. Lahiri, Jeffrey J. Lennox, Andrea Knezevic, Kirk A. Easley, M. N. Weitzmann Emory Univ, Atlanta, GA, USA Background: HIV infection and antiretroviral therapy (ART) are associated with bone loss leading to increased fracture rate in the HIV/AIDS population. Although the ART bone effects vary in magnitude, they appear to be universal to all regimen types and most intense in the first year of therapy, creating a window for prophylactic intervention. We previously showed that the long-acting antiresorptive zoledronic acid (ZOL) prevented ART bone effects through the first 48 weeks of therapy and here investigate whether these effects persisted. Methods: We randomized 63 non-osteoporotic, viremic treatment-naïve adult HIV-infected subjects initiating ART to a ZOL (5mg) vs. placebo (PL) infusion in a double-blinded, placebo-controlled phase IIb clinical trial. Laboratory and safety measurements, plasma bone turnover markers, and bone mineral density (BMD) were performed at weeks 0, 12, 24, 48, 96, and 144. Repeated-measures analyses using mixed linear models were used to estimate and compare study endpoints. Results: As shown in Figure 1, the ZOL arm had a 55% reduction in mean bone resorption (i.e., C-terminal telopeptide of collagen [CTx]) at 48 weeks relative to the placebo arm (CTx=0.120 ng/mL vs 0.268 ng/mL; p<0.001) and 62% lower at 96 weeks (n=41; 0.119 ng/mL vs 0.315 ng/mL; p=0.002). A 30% difference observed between the arms at 144 weeks was however not statistically significant (n=37; 0.137 ng/mL vs 0.195 ng/mL; p=0.13). A compensatory increase in osteocalcin (a marker of bone formation) was observed in the placebo arm but not in the ZOL arm. The ZOL arm had an 11% higher lumbar spine BMD at 48 weeks relative to the placebo arm (n=60; 1.30 g/cm2 vs 1.17 g/cm2; p<0.001) and remained 9-11% higher at 96 weeks (n=46) and 144 weeks (n=41, 1.31 g/cm2 vs 1.18 g/cm2; p <0.001; mean difference=0.13, 95% confidence interval 0.06, 0.21 g/cm2). Similar trends were observed in the hip and the femoral neck bones and ZOL did not result in long-term toxicities. Conclusion: Our data suggest that ART enhanced bone resorption and BMD loss extend beyond the first 2 years of therapy and that a single dose of ZOL given at the time of therapy initiation durably blunt these effects at key fracture prone anatomical sites. These beneficial outcomes continued throughout the 3-year follow-up period. ZOL was well tolerated, preserved bone density, and ZOL or another similar intervention should be tested in a larger group of subjects.

Poster and Themed Discussion Abstracts

685LB HIGH DOSE VITAMIN D3 INCREASES SPINE BONE DENSITY IN HIV+ YOUTH ON TENOFOVIR (TDF) Peter L. Havens 1 , Charles Stephensen 2 , Marta Van Loan 2 , Brandy Rutledge 3 , Bob Harris 3 , Patricia M. Flynn 4 , Catherine Gordon 5 , Bill Kapogiannis 6 , Kathleen Mulligan 7 , for the Adolescent MedicineTrials Network for HIV/AIDS Interventions (ATN) 109 StudyTeam 1 Med Coll of Wisconsin, Wauwatosa, WI, USA, 2 USDA, Davis, CA, USA, 3 Westat, Rockville, MD, USA, 4 St. Jude Children’s Rsr Hosp, Memphis, TN, 5 Univ of Cincinnati, Cincinnati, OH, 6 NICHD, Bethesda, MD, USA, 7 Univ of California San Francisco, San Francisco, CA, USA Background: Tenofovir disoproxil fumarate (TDF) decreases bone mineral density (BMD). Vitamin D (VITD) supplementation increases BMD in persons with VITD deficiency. We hypothesized that VITD administration would increase BMD in youth with HIV treated with TDF, independent of baseline VITD status. Methods: Randomized double blind placebo controlled trial of directly observed oral VITD3 50,000 IU vs. placebo every 4 weeks for 48 weeks in youth, ages 16-24 years, HIV viral load <200 copies/mL, taking TDF-containing cART for ≥180 days. All participants (N=212) received a daily multivitamin containing VITD3 400 IU and calcium (Ca) 162 mg in addition to randomized VITD (‘high dose group’; N=108) or placebo (‘low dose group’; N=104). Primary outcome was change from baseline to week 48 in lumbar spine (L1-L4) BMD (LSBMD) measured by DXA. The study was designed for 90% power to detect a between-group difference in LSBMD percent change ≥1.8% at week 48. Completed June, 2016. Nonparametric testing was used to assess differences from baseline to week 48 and differences between VITD dose groups. Data presented as mean±standard deviation except LSBMD percent change is median (interquartile range). Results: Age was 21.8±1.8 years; 84%were male and 74% black/African American. At baseline, VITD dose groups were similar in age, race/ethnicity, and Ca intake; low dose group had lower BMI, lower VITD intake and lower multivitamin use. Overall, baseline 25-hydroxyvitamin D (25-OHD) was 18.7±9.6 ng/mL. Prevalence of VITD deficiency (25-OHD <20 ng/mL) was 62%, with no randomized group differences. Daily multivitamin adherence was 48±24% and randomized study medication adherence was 96±8%. From baseline to week 48, LSBMD increased by 0.70% overall (P<0.001), increasing by 1.15% in the high dose group (P<0.001) and 0.09% in the low dose group (P=0.25), with no significant difference between groups (Table; P=0.12). ). In the high dose group these changes occurred in participants with baseline 25-OHD < 20 ng/mL (1.17%; P=0.004) and with baseline 25-OHD ≥20 ng/mL (0.93%; P=0.03).There were no significant changes in hip or whole-body BMD. Conclusion: For HIV-infected adolescents and young adults treated with TDF-containing cART, high dose, but not low dose, VITD3 supplementation administered every 4 weeks increased LSBMD through 48 weeks, independent of baseline VITD status.

CROI 2017 298