CROI 2015 Program and Abstracts

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Oral Abstracts

the placebo arm) and 3 gastrointestinal side effects (1 and 2, respectively). At least one depressive episode related to trial treatment was reported in 1 and 7 patients, respectively. Among 7 grade 3/4 cardiovascular events, 4 occurred in the varenicline arm (not treatment related) and 3 in the placebo arm. No neurovascular event was reported. Conclusions: Varenicline is safe and effective in HIV infected patients with a 34% rate of tobacco abstinence at 12 weeks (end of treatment) and 18% at 48 weeks. These results are in the range of those reported in the HIV uninfected population. Varenicline should be considered as part of the standard of care in HIV-infected patients motivated to quit smoking. 140 Body Composition Changes After Initiation of Raltegravir or Protease Inhibitors Grace A. McComsey 1 ; Carlee Moser 2 ; Judith S. Currier 8 ; Heather Ribaudo 2 ; Pawel Paczuski 2 ; Michael P. Dube 5 ; Robert L. Murphy 6 ; Jennifer Rothenberg 7 ; James H. Stein 4 ;ToddT. Brown 3 1 Case Western Reserve University, Cleveland, OH, US; 2 Harvard School of Public Health, Center for Biostatistics in AIDS Research, Boston, MA, US; 3 Johns Hopkins University School of Medicine, Baltimore, MD, US; 4 University of Wisconsin School of Medicine and Public Health, Madison, WI, US; 5 University of Southern California, Los Angeles, CA, US; 6 Northwestern University, Chicago, IL, US; 7 Social & Scientific Systems, Inc., Silver Spring, MD, US; 8 University of California Los Angeles, Los Angeles, CA, US Background: Although lipoatrophy is uncommon with current antiretroviral therapy (ART), fat accumulation continues to occur, and its association with protease inhibitors (PIs) has been questioned. The effect of integrase inhibitors vs. PIs on body composition has not been established. Methods: We compared the percentage change in lean mass (by DXA), peripheral fat (limb fat by DXA and subcutaneous abdominal fat (SAT) by CT scan of abdomen), and central fat (trunk fat by DXA and visceral abdominal fat (VAT) by CT) over 96 weeks in HIV-infected treatment-naive participants randomized to open labeled tenofovir disoproxil fumarate-emtricitabine (TDF/FTC) plus atazanavir-ritonavir (ATV/r), darunavir-ritonavir (DRV/r), or raltegravir (RAL) in ACTG 5260s, a substudy of A5257. DXA and CT measurements were standardized and centrally read. Linear regression, adjusting for the stratification factors of baseline cardiometabolic risk and HIV-1 RNA, was used to compare the 96-week percentage change in fat and lean mass in the two PI arms (ATV/r vs DRV/r) and, if not different, the PI arms were combined and compared to RAL arm. Associations between baseline biomarkers and changes in body composition were assessed with linear regression models adjusting for baseline age, BMI, HIV-RNA, CD4 count, sex and race/ethnicity. Within arm changes were assessed with signed-rank tests. All analyses were intent-to-treat. Results: 328 participants were randomized; 90%were male and 44%white, non-Hispanic; median age was 36 years, HIV-1 RNA load 4.55 log10 copies/mL, and CD4 count 349 cells/ μ L. At week 96, the median percentage increases in limb fat, SAT, VAT, trunk fat, and lean mass were statistically significant in all arms (8.2%, 10.9%, 13.9%, 11.4%, 1.3%; p<0.001). Changes for all fat outcomes were not different between the PI arms (p ≥ 0.36), however greater gains in lean mass with ATV/r vs. DRV/r were detected (3.8% vs. 2.3%; p=0.05). There were no significant differences between the RAL arm and combined PI arm in any fat or lean mass endpoints (p ≥ 0.36). While lower baseline leptin and higher RNA levels were associated with greater gains in peripheral and central fat, higher baseline IL-6 was only associated with greater gains in peripheral fat. Conclusions: In ART-naïve subjects initiating ART with TDF/FTC, RAL led to similar increases in lean mass, and central and peripheral fat as compared to ATV/r and DRV/r. We saw no evidence to suggest that the PIs were associated with greater increases in central fat than RAL 141 Fracture PredictionWith Modified FRAX in Older HIV+ and HIV- Men Michael T. Yin 1 ; Melissa Skanderson 7 ; Stephanie Shiau 1 ; Katherine Harwood 1 ; Josh Aschheim 3 ; David Rimland 2 ; Cynthia Gibert 5 ; Maria Rodriguez-Barradas 4 ; Roger Bedimo 6 ; JulieWomack 7 1 Columbia University Medical Center, New York, NY, US; 2 VAMC and Emory School of Medicine, Atlanta, GA, US; 3 Arcadia Healthcare Solutions, New York, NY, US; 4 Baylor College of Medicine, Houston, TX, US; 5 VA Medical Center, George Washington University, Washington, DC, US; 6 University of Texas, Dallas, TX, US; 7 VA Connecticut Healthcare System, West Haven, CT, US Background: Fracture rates are increased in HIV+ individuals. FRAX is a web-based fracture risk calculator used with or without bone mineral density (BMD) that estimates absolute 10-year risk of major osteoporotic (hip, spine, forearm, shoulder) and hip fracture. It is widely used for decision making in screening and treatment for fracture prevention. Since FRAX may underestimate fracture risk in HIV+ individuals; some experts recommend adding ‘secondary osteoporosis’ as a surrogate for HIV infection when using FRAX in an HIV+ patient. Methods: From the Veterans Aging Study Virtual Cohort (VACS-VC), 26,037 HIV+/HIV- 50-70 year-old men were selected for whom complete data were available in 2000 to approximate all but 2 factors for FRAX calculation without BMD (history of secondary osteoporosis and parental hip fracture). Sum of estimated rates by this modified FRAX calculation was compared to observed 10-year fracture rates at similar body sites. Calibration (agreement between observed outcomes and predictions) by observed to estimated ratios (O/E) and discrimination (ability to discriminate subjects with and without outcome) by area under the curve (AUC) were compared by HIV status Results: In 2000, HIV+men were similar in age (56 ± 5 vs 56 ± 5, p=0.11) to HIV- men, but had lower weight (79 ± 15 vs 89 ± 16 kg, p<0.01), were more likely to report previous fracture, alcohol and glucocorticoid use, and less likely to smoke or have rheumatoid arthritis. More fractures occurred in HIV+ than HIV- men at major osteoporosis sites (4.61 vs 3.50%, p<0.01) and hip (1.32 vs 0.85%, p<0.01). Estimated rates by the modified FRAX were also higher for HIV+ than HIV- men at major osteoporosis sites (2.85 ± 1.5 vs 2.71 ± 1.4%, p<0.01) and hip (0.29 ± 0.4 vs 0.24 ± 0.3%, p<0.01). Calibration for major osteoporotic fracture was worse in HIV+ than HIV- men (1.62 vs 1.29, p=0.028). Discrimination for modified FRAX was poor, but did not differ by HIV status (Table). Adding ‘secondary osteoporosis’ as a surrogate for HIV-infection risk in FRAX calculation improved calibration to level of HIV- men (O/E=1.20), but did not improve discrimination (AUC=0.600). Conclusions: In this study of older men, the modified FRAX score underestimates fracture rates more in HIV+ than HIV- men, and does not discriminate well between those at risk and not at risk for future fracture. Including ‘secondary osteoporosis’ as a surrogate risk factor may improve the performance of the modified FRAX in HIV+ patients. 142 Exposure to Antiretrovirals (ARVs) and Development of Chronic Kidney Disease (CKD) Amanda Mocroft 1 ; Jens D. Lundgren 2 ; Michael Ross 3 ; Christoph Fux 4 ; Peter Reiss 5 ; Olivier Moranne 6 ; Philippe Morlat 7 ; Antonella d’Arminio Monforte 8 ; Ole Kirk 2 ; Lene Ryom 2 On behalf of theThe Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) Study Group 1 UniversityCollegeLondon,London,UnitedKingdom; 2 CopenhagenHIVProgramme,Centre forHealthand InfectiousDiseasesNetwork,UniversityofCopenhagen,Denmark,Denmark; 3 DivisionofNephrology,Mount SinaiSchoolofMedicine,NewYork,NY,US; 4 Clinic for InfectiousDiseasesandHospitalHygiene,KantonsspitalAarau,Aarau,Switzerland; 5 AcademicMedicalCenter,Div.of InfectiousDiseasesandDept.ofGlobalHealth, UniversityofAmsterdam,Amsterdam,Netherlands; 6 UniversitédeBordeaux, InsermU897,Bordeaux,France; 7 PublicHealthDepartment,Nice,France; 8 IstitutoDiClinicaMalattie InfettiveeTropicale,Milan, Italy Background: Previous studies in persons with an initially normal eGFR have been underpowered to assess whether the incidence of CKD increases immediately after starting potentially nephrotoxic ARVs and then remains stable or continues to increase with duration of exposure. Methods: D:A:D study participants were followed frombaseline until earliest of CKD, last eGFR, 1/1/2013 or last visit plus 6 months. Baseline was defined as the first eGFR after 1/1/2004; persons with <2 eGFRs after baseline or where baseline eGFR<90 ml/min/1.73m 2 were excluded. CKDwas defined as confirmed (>3months apart) eGFR <60ml/min/1.73m 2

Oral Abstracts

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CROI 2015