CROI 2016 Abstract eBook

Abstract Listing

Oral Abstracts

40 Efavirenz Is AssociatedWith Higher Bone Mass in South African ChildrenWith HIV Stephen M. Arpadi 1 ; Stephanie Shiau 1 ; Renate Strehlau 2 ; Faeezah Patel 2 ; Louise Kuhn 3 ; Ashraf Coovadia 2 ; Don McMahon 1 ; Jonathan J. Kaufman 4 ; MichaelT.Yin 1 ; for the CHANGES Bone StudyTeam 1 Columbia Univ Med Cntr, New York, NY, USA; 2 Univ of the Witwatersrand, Johannesburg, South Africa; 3 Columbia Univ, New York, NY, USA; 4 Mount Sinai Sch of Med, New York, NY, USA Background: Ritonavir-boosted lopinavir (LPV/r) is recommended as the first line regimen for HIV-infected children but has limitations for long term use. A randomized clinical trial was undertaken in Johannesburg, South Africa to evaluate the safety and efficacy of pre-emptive switching to efavirenz (EFV) vs. remaining on LPV/r in children initially suppressed on LPV/r. The primary results of the trial have been previously reported but here we investigate whether the switch to EFV is associated with beneficial outcomes in terms of bone development. HIV infection affects bone accrual but there are limited data on how to optimize antiretrovirals to improve bone outcomes in children. Methods: 220 HIV-infected children aged 5-10 years (mean 6.4) were enrolled 1-4 years (mean 2.1) after randomization in the trial. 180 similarly-aged HIV-uninfected children were recruited at the same site in Johannesburg for comparison. Physical activity (PA) and dietary intake were assessed by questionnaire. Bone mineral content (BMC), fat mass, and lean body mass of the whole body (WB) were was assessed by DXA (Hologic Discovery W). Sex-specific BMC-for-height Z-scores for the infected children were generated using the BMC-for-height distribution of the uninfected controls. Children with HIV currently receiving EFV were compared to those on LPV/r. Results were adjusted for age, fat mass, lean mass, vigorous PA, and dietary vitamin D and calcium, CD4, and viral load. Analyses were also stratified by sex. Intent-to-treat analyses based on the original assigned regimen were also done. Results: Among HIV-infected children 110 were on EFV and 110 LPV/r at the time of assessment. All children were also on 2 NRTIs, including 3TC and ABC, AZT, or d4T. None were on TDF. The BMC Z score was -0.49 in the EFV group and -1.07 in the LPV/r group. This association remained significant (p<0.001) and of a similar magnitude (Z-score difference 0.58) after adjustment for age, fat mass, lean mass, vigorous PA, dietary vitamin D and calcium, CD4, and viral load. Sex-stratified analysis showed similar size effects in both boys and girls. In intent-to-treat analyses based on the originally assigned regimen, results were similar. Higher fat and lean body mass were also independently associated with better bone mass outcomes. Conclusions: Accrued bone mass is positively associated with switching to EFV-based ART (compared to remaining on LPV/r). Use of bone friendly drugs may be beneficial for bone health in children with HIV. 41 Early Antiretroviral Therapy Does Not Improve Vascular Function: A START Substudy Jason V. Baker 1 ; Katherine Huppler Hullsiek 2 ; NicoleWyman Engen 2 ; Daniel Duprez 2 ; for the INSIGHT START (StrategicTiming of AntiRetroviralTreatment) Arterial Elasticity SubStudy Team 1 Hennepin County Med Cntr, Univ of Minnesota, Minneapolis, MN, USA; 2 Univ of Minnesota, Minneapolis, MN, USA Background: Both HIV infection and antiretroviral therapy (ART) may increase cardiovascular disease (CVD) risk. Assessments of vascular function can be used to study the pathogenesis and progression of CVD. We compared the effect of early ART initiation (CD4 counts >500 cells/mm 3 ) with untreated HIV/deferred ART (until CD4 < 350 cells/mm 3 ) on small and large arterial elasticity (SAE and LAE) among a subset of ART-naïve adults in the START trial. Methods: Radial artery waveforms were recorded non-invasively using a tonometer at baseline, months 4, 8, 12, and then annually. SAE and LAE were derived from analysis of the diastolic pulse waveform (CR2000, HDI). Randomized treatment groups (early vs. deferred ART) were compared with linear models at each visit and longitudinal mixed models overall. Additional analyses included censoring deferred group participants who started ART and for protocol-specified subgroups. Results: Among 332 participants at 21 sites in 8 countries on 6 continents: mean (SD) age was 35 (10), 70%male, 66% non-white, 30% smokers, 5% taking BP-lowering therapy, 3% taking lipid lowering therapy, and median [IQR] duration of HIV diagnosis 1.3 years [0.4, 3.1], CD4 count 625 cells/mm 3 [562, 729], HIV RNA 4.2 log10 copies/mL [3.7, 4.7], and 10-year Framingham risk score for coronary heart disease 1.2% [0.3, 4.2]. Mean (SD) SAE and LAE values at baseline were 7.3 (2.9) mL/mmHg x100 and 16.6 (4.1) mL/mmHg x10, respectively. Median follow-up was 40 months. Median time on ART was 30 and 7 months in the early and deferred ART groups, respectively. Neither treatment group demonstrated significant within-person changes in SAE or LAE over follow-up. Differences in SAE and LAE between early and deferred ART over time are shown in the table. The lack of significant differences persisted in comparisons restricted to ≤1 (or >1) year of follow-up, after censoring participants in deferred group who started ART, and among subgroups defined by CVD and HIV risk factors. Conclusions: Among a diverse global population of HIV+ persons with high CD4 counts, early ART initiation did not improve arterial elasticity. These randomized data suggest that early ART treatment may not have a substantial influence vascular function among younger HIV+ individuals with preserved immunity.

Oral Abstracts

42 Comparing Cardiovascular Disease Risk Scores for Use in HIV-Infected Individuals

Heidi M. Crane 1 ; Robin Nance 1 ; Joseph A. Delaney 2 ; Daniel Drozd 1 ; Susan Heckbert 1 ; RebekahYoung 1 ; Matthew J. Feinstein 3 ; Richard Moore 4 ; Michael S. Saag 5 ; Mari M. Kitahata 1 1 Univ of Washington, Seattle, WA, USA; 2 Univ of Washington Sch of PH, Seattle, WA, USA; 3 Northwestern Univ, Feinberg Sch of Med, Chicago, IL, USA; 4 Johns Hopkins Univ, Baltimore, MD, USA; 5 Univ of Alabama at Birmingham, Birmingham, AL, USA Background: While cardiovascular disease (CVD) risk stratification tools exist for use in the general population, they may not accurately estimate risk in persons living with HIV (PLWH). Examining the performance of CVD risk scores in PLWH requires large studies with comprehensive clinical data and well-validated outcomes. Methods: We developed a state-of-the-art screening algorithm and central adjudication protocol for the validation of incident myocardial infarction (MI) in the CFAR Network of Integrated Clinical Systems (CNICS), which harmonizes comprehensive clinical data on PLWH in routine care at multiple US sites. Among PLWH enrolled between 1996-2014, we compared the performance of 3 CVD risk scores developed in the general population (Framingham, ATP-3, and 2013 ACC/AHA ASCVD) and one developed for use in PLWH (D:A:D) using area under the curve (AUC). The Universal Definition of MI classifies MI by type. Type 1 MI (T1MI) result spontaneously from atherosclerotic plaque instability, whereas type 2 MI (T2MI) occur secondary to oxygen demand/supply mismatch of any cause such as sepsis. We compared the AUC for risk scores for T1MI, T2MI, and all MIs combined. Beginning in 2007, CNICS patients completed clinical assessments every 4-6 months that included tobacco use. We repeated analyses among this subset to ensure smoking status was updated for those who quit or started smoking.

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CROI 2016