CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

Conclusions: Despite prolonged and high-dose exposure to NRTIs, there is no mutagenesis in mtDNA. However, we observed: 1) a selective advantage to the replication of deleted mtDNA (ddI and high-dose d4T); and 2) the enhanced segregation of mtDNA point mutations through a molecular bottleneck mechanism (ddI). Both phenomena will in vivo lead to accelerated clonal expansion of pre-existing (age-associated) mtDNA mutations within individual cells. These data provide a plausible mechanism for increased mtDNA mutations observed in NRTI-treated patients. Such mutations may lead to accelerated physiological decline during aging. 786 Balance Confidence Predicts Falls Better Than Physical Function Testing in HIV+Men Todd T. Brown 1 ; Xiuhong Li 2 ; Lisa P. Jacobson 2 ; Jennifer Schrack 2 ; Frank J. Palella 3 ; Lawrence Kingsley 4 ; Joseph B. Margolick 2 ; Adrian Dobs 1 ; Jordan Lake 5 ; Keri N. Althoff 2 MACS 1 Johns Hopkins University School of Medicine, Baltimore, MD, US; 2 Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, US; 3 Northwestern University, Feinberg School of Medicine, Chicago, IL, US; 4 University of Pittsburgh, Pittsburgh, PA, US; 5 University of California Los Angeles, Los Angeles, CA, US Background: Falls are a major source of morbidity in older adults. Tests of physical function and questionnaires of self-reported balance confidence have been used to predict fall risk in older HIV-uninfected (HIV-) persons, but these assessments have not yet been validated in HIV-infected (HIV+) persons. Methods: HIV+ and HIV- men who have sex with men 50-70 years old were recruited from the Multicenter AIDS Cohort Study (MACS) for a substudy assessing fracture risk. At baseline, participants underwent clinical tests of balance (Functional Reach Test, Standing Balance Test), strength (grip strength, chair stands), gait speed, composite measurements of physical function (Short Physical Performance Battery), and a short questionnaire assessing balance confidence during various activities (Activities Balance Confidence (ABC), which assesses balance confidence on a scale of 0-100% during 6 activities (<80%=low confidence)). Falls were reported prospectively over a two-year period (median follow up time (IQR) 14.7 (12.3-16.5) months). The relationships between clinical tests of physical function/ABC and falling status (faller vs non-faller) were determined with logistic regression. All analyses were adjusted for age, race, education, body mass index, MACS site, and HIV serostatus. Results: During the follow-up period, 27% (65/238) of HIV+men and 23% (69/298) of HIV- men reported at least one fall (p=0.28); 11% of HIV+men and 9% of HIV- men reported ≥ 2 falls (p=0.40). Overall, lower balance confidence (<80% vs ≥ 80% on ABC) was significantly associated with having a fall (adjusted odds ratio (aOR) 2.24 [95% confidence interval (CI); 1.38, 3.66]). In contrast, lower performance on physical function tests showed no association with falling(p>0.099 for each test). Similar results were observed for the relationship of these assessments with having 2 or more falls. Among the HIV+men, lower balance confidence also predicted falling (aOR 4.25 (95%CI:1.93, 9.35), p<0.001), but physical function tests did not (p>0.07 for each test). Conclusions: HIV serostatus was not associated with incident falls in this population of older men. Self-reported balance confidence was a significantly better predictor of falls than standard clinical tests of strength and balance, and could be easily incorporated into clinical practice to identify HIV-infected patients at greater risk of falls.

TUESDAY, FEBRUARY 24, 2015 Session P-Q7 Poster Session

Poster Hall

2:30 pm– 4:00 pm Diabetes and Other Endocrine Disorders 787 Vitamin D Supplementation Does Not Affect Metabolic Changes SeenWith ART Initiation Todd T. Brown 1 ; Ellen Chan 2 ; EdgarT. Overton 3 ; PabloTebas 4 ; Kathy Melbourne 5 ; Royce Hardin 6 ; Heather Ribaudo 2 ; MichaelT.Yin 7 ACTG

1 Johns Hopkins University School of Medicine, Baltimore, MD, US; 2 Harvard School of Public Health, Center for Biostatistics in AIDS Research, Boston, MA, US; 3 University of Alabama at Birmingham, Birmingham, AL, US; 4 University of Pennsylvania, Philiadelphia, PA, US; 5 Gilead Sciences, Inc., Foster City, CA, US; 6 Duke University, Durham, NC, US; 7 College of Physicians and Surgeons, Columbia University, New York, NY, US Background: Insulin resistance and lipid changes are commonly seen after ART initiation. Observational studies suggest that vitamin D supplementation reduces the risk of developing diabetes and improves lipid profiles. Methods: This 48-week prospective, randomized, double-blind, placebo-controlled study evaluated the effect of high dose vitamin D3 (4000 IU daily) plus calcium supplementation (1000 mg calcium carbonate daily) in HIV-infected subjects initiating ART with efavirenz/emtricitabine/tenofovir. In this secondary analysis, changes in insulin resistance (as measured by HOMA-IR), lipid profile, and components of the metabolic syndrome were assessed at baseline, 24 and 48 weeks using the intent-to-treat approach. Stratified Wilcoxon rank sum tests and stratified normal score tests were used to test for differences between the two treatment groups, stratified by screening 25-OH vitamin D stratum ( ≤ /> 20 ng/mL). A more conservative significance level 0.01 was used in order to adjust for multiple testing. Results: 165 eligible subjects enrolled, with 79 in Vitamin D/Calcium (Vit D/Cal) group and 86 in placebo group. The placebo group but not the VitD/Cal group experienced modest increase in insulin resistance at week 24 (P<0.001). While increases in total and HDL cholesterol were apparent in both groups at weeks 24 and 48, increases in LDL cholesterol at week 24 were only marginal in the placebo group (P=0.011). BMI was stable over the course of the study, whereas modest increases in waist circumference were observed at week 24 that were not persistent at week 48. Metabolic syndrome was present in 19 subjects (12%) at baseline and 20 subjects (14%) at week 48 without differences between groups. There were no between group differences in any of these metabolic parameters at either 24 or 48 week evaluations (P ≥ 0.17).

Poster Abstracts

480

CROI 2015