CROI 2015 Program and Abstracts

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Oral Abstracts

Results: We found that Gag+ cells were strongly (more than 100-fold) enriched for HIV DNA compared to Gag-negative cells in infected cultures. In addition to spliced HIV RNA forms, further evidence of nascent transcription included direct and indirect evidence of new synthesis of multiple HIV proteins by FACS. Read-through transcripts were detectable but present at low levels compared to gag RNA in both cells infected in vitro and in CD4 cells from ART patients. Stimuli such as IL-7 and Romidepsin preferentially induced gag usRNA over read-through transcripts. In contrast, SAHA induced both read-through and gag usRNA transcription two-fold. Notably, we show that low-level protein expression can occur in the absence of tat/rev using a viral vector with a deletion of tat/rev gene expression. Conclusions: Nascent LTR transcription occurs in HIV-infected resting CD4+ T cells. In vitro and in vivo data suggest that Gag is the predominant transcript (usRNA) and protein expressed in HIV infected individuals on ART. The relative contributions of replication competent and defective proviruses to viral protein expression in vivo remain undefined. 778 Obesity and Inflammation in Resource-Diverse Settings of ART Initiation Kristine M. Erlandson 1 ; Nikhil Gupte 2 ; Javier R. Lama 3 ; Patcharaphan Sugandhavesa 4 ;Thando Mwelase 5 ; Ashwin Balagopal 2 ; David Asmuth 6 ;Thomas B. Campbell 1 ; Amita Gupta 2 On behalf of the A5175 and NWCS319 study team 1 University of Colorado, Aurora, CO, US; 2 Johns Hopkins University, Baltimore, MD, US; 3 Impacta Peru Clinical Trials Unit, Lima, Peru; 4 Chiang Mai University, Chiang Mai, Thailand; 5 University of Witswatersrand, Johannesburg, South Africa; 6 University of California Davis, Sacramento, CA, US Background: The heightened inflammatory profile resulting from both HIV infection and obesity is of increasing importance in many HIV-related comorbidities. Little is known about the association between the change in body mass index (BMI) with antiretroviral (ART) initiation and the change in inflammatory markers, particularly in resource-limited settings. Methods: AIDS Clinical Trials Group study A5175 was a randomized trial comparing 3 ART regimens in resource-diverse international settings; the following is a country stratified random sub-cohort of 270 subjects; 246 subjects had stored samples. BMI (weight [kg]/height [m] 2 ) was categorized as underweight (UW, <18.5), normal weight (NW, 18.5-24.9), and overweight/obese (OW/OB, ≥ 25.0). Inflammatory markers were measured (TNF- α , IFN- γ , IL-6, IL-18, IP-10, CRP, sCD14) at weeks 0, 24, 48. Effect of baseline and change in BMI on changes in biomarkers was assessed using random effects models fitted for natural spline at BMI categories and adjusted for age, sex, country, log 10 HIV-1 RNA, and treatment arm. A separate model assessed the effect of change to OB BMI (>30 versus ≤ 30). Results: Of 246 participants, 50%were female, 53% black, with a median age 35 and CD4 count 179. 37%were assigned to ZDV/3TC+EFV, 33% to ATV+FTC+DDI, and 30% to TDF/FTC+EFV. At week 0, 8%were UW, 65% NW, 27% OW/OB including 7% OB; at week 48, 3%were UW, 60% NW, 37% OW/OB including 9% OB. In multivariate analyses, among baseline UW subjects, an incremental BMI increase was associated with decreased CRP ( β -9.32; p=0.001) and trend towards decreased sCD14 ( β -0.09; p=0.09). For baseline OW/ OB subjects, an increase in BMI was associated with increased sCD14 ( β 0.02; p=0.05). No significant associations were detected in the NW group or within other inflammatory markers (p>0.05). In multivariate analyses comparing OB vs not OB participants, OB was associated with an increase in sCD14 ( β 0.19; p=0.02) and trend towards higher IL-18 ( β 127.7; p=0.056); there were no associations with other markers. Conclusions: Among HIV-infected persons initiating ART in resource-diverse settings, weight gain among underweight persons may reduce inflammation. In contrast, weight gain among obese persons appeared to heighten inflammation. As sCD14 is a marker of mortality during HIV treatment, the data highlight the potential impact of obesity on treatment outcomes. Further investigation into the impact of obesity on HIV treatment outcomes in resource-limited settings is needed. 779 Body Composition Outcomes at 96Weeks in the SECOND-LINE RCT DXA Substudy Mark A. Boyd 1 ; Janaki Amin 1 ; PatrickW. Mallon 2 ; Jennifer F. Hoy 3 ; Samuel Ferret 4 ;Waldo Belloso 5 ; Praphan Phanuphak 6 ; Sean Emery 1 ; David A. Cooper 1 SECOND-LINE study group 1 University of New South Wales Australia, Sydney, Australia; 2 University College Dublin, Dublin, Ireland; 3 Monash University/Alfred Hospital, Melbourne, Australia; 4 Hopital Saint Louis, Paris, France; 5 Hospital Italiano, Buenos Aires, Argentina; 6 Thai Red Cross AIDS Research Centre, Bangkok, Thailand Background: Antiretroviral therapy (ART) should optimally cause minimal harm. Preferred N(t)RTI-backbones are associated with toxicities with poorly understood long term consequences. In the SECOND-LINE study we demonstrated non-inferiority (margin=12%) of ritonavir-boosted lopinavir (r/LPV) plus raltegravir (RAL-arm) compared to r/LPV plus 2-3N(t)RTI regimen (N(t)RTI-arm) after virological failure of standard NNRTI+2N(t)RTI first-line ART. The RAL-armwas associated with significantly less bone mineral density (BMD) loss. We hypothesised that the RAL-armwould be associated with a greater degree of limb fat gain at 96 weeks. Methods: We performed a DXA-substudy of SECOND-LINE at weeks 0, 48 and 96 at 8 sites in Argentina, India, Malaysia, South Africa and Thailand. Primary endpoint was the mean percent change from baseline in peripheral limb fat. Analysis was by intention to treat (ITT). We adjusted for baseline imbalances in sex, BMI and smoking. Multivariate linear copies/mL, CD4+ count 220 (167) cells/ m L, first-line ART duration 3.3 (1.9-5.9) years, 34%% and 48% on d4T and AZT respectively prior to initiating randomised ART. Eighty six percent and 42% N(t)RTI arm study participants received TDF and AZT respectively. After 96 weeks the mean (SD)% limb fat change from baseline was 16.8 (32.6)% in the N(t)RTI-arm and 28.0 (37.6)% in the RAL-arm, a mean difference (95% CI) of 10.2 (0.1-20.4)% (p=0.048). Baseline predictors of percent changes in limb fat mass over 96 weeks are shown in Table 1. regression was used to assess between-group differences and predictors of percent change in limb fat mass. Results are mean (SD) and median (IQR). Results: Baseline characteristics of the 210 enrolled participants: 110 (52%) female, age 38.6 (7.8) years, 52% Asian/43% African, HIV RNA 4.1 (1.0) log 10

Oral Abstracts

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CROI 2015