CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

and Interleukin (IL)-6, IL-7, and IL-15. In the cART-E group, IBs were measured at study entry, 2 years and 6 years. We stratified the 3 IB samples by number of years receiving continuous cART. We used the Kruskal-Wallis test of medians to compare IB levels from the cART-E vs. the cART-N and HNC groups. Results: Over the 10 years following initiation of ART, IB levels in the cART-E group were significantly higher vs. those of HNCs (p < 0.05) excepting IL-7 which was not significantly different (NS) vs. HNCs. In the first 4-5 years IB levels in the cART-E groups initially rose and then declined to levels below those of the cART-N group but the differences were NS with the exception of MIP-1 alpha that was lower for the last 3 years and IL-6, IL-15, and MCP-1 that were lower in year 10 (p < 0.05, for all). For each year, there were no significant differences in IBs in the PI vs. NNRTI groups.

Conclusions: After 10 years of cART, levels of IBs decline but remain elevated vs. HNCs. There were no significant differences in levels seen with PI vs. NNRTI based cART. 313 Persistently High IL-18 and sCD14 Are Independently AssociatedWith Clinical Failure Ashwin Balagopal 1 ; Nikhil Gupte 1 ; James Hakim 2 ; Mina C. Hosseinipour 3 ; Nagalingeswaran Kumarasamy 4 ; Andrea Cox 1 ; Ian Sanne 7 ; David Asmuth 5 ;Thomas Campbell 6 ; Amita Gupta 1 On behalf of the ACTG 1 Johns Hopkins University School of Medicine, Baltimore, MD, US; 2 University of Zimbabwe, College of Health Sciences, Harare, Zimbabwe; 3 University of North Carolina, Chapel Hill, NC, US; 4 Y.R.G. Care, Chennai, India; 5 University of California San Diego, San Diego, CA, US; 6 University of Colorado, Denver, CO, US; 7 ACTG, Washington, DC, US Background: Inflammation drives clinical progression in HIV-infected persons. Antiretrovirals (ARV) partially reduce inflammation. We studied the effect of persistent inflammation on clinical failure during ARV among multi-country ACTG 5175 trial participants. Methods: In a nested case-control study, cases were clinical failure, defined as incident WHO stage 3/4 HIV disease or death fromweeks 24 to 96 weeks; controls were without clinical failure and randomly selected. IL-6, IP-10, IL-18, TNF α , IFN γ and sCD14 levels were measured pre-ARV and at week 24 of ARV (ARV24). Persistent inflammation was defined as highest quartile levels (>Q3) pre-ARV and at ARV24 for IL-6(>48.3pg/mL),IP-10(>2856pg/mL),IL-18 (>774pg/mL), sCD14 (>6.4log 10 pg/mL), TNF α (>28.4pg/mL), and IFN γ (>48pg/mL), compared to lower quartiles( ≤ Q3). Poisson regression analysis was used to estimate RRs, adjusting for baseline age, sex, treatment, country, CD4, log 10 HIV RNA, prevalent TB, and viral suppression at ARV24 (HIV RNA<400 cp/ml). Results: Of 99 cases and 233 controls, available samples were tested ( Figure ). Median age was 34 years; 160 (48%) were females. Median (IQR) CD4 was 181 (96-229) cells/ μ L and median (IQR) HIV RNA level was 5 (4.5-5.5) log 10 cp/mL. At ARV24, 276 (87%) persons were virologically suppressed; median (IQR) CD4+ T cell count was 290 (197-388) cells/ μ L. Persistently high levels of IL-18 and sCD14 at ARV24 were independently associated with clinical failure [IL-18 RR (95%CI) 3.59 (1.48–8.74), p<0.05; sCD14 RR (95%CI) 2.21 (1.01–4.80), p<0.05]. High levels of IFN γ were independently associated with decreased risk of clinical failure [RR (95%CI) 0.08 (0.01–0.66), p<0.05]. Other markers at ARV24 were not associated with clinical failure. Restricting the analysis to subjects who were virologically suppressed at ARV24 maintained associations with IL-18 and IFN γ [IL-18 RR (95%CI) 3.10 (1.08–9.02), p<0.05; IFN γ RR (95%CI) 0.07 (0.01 – 0.64), p<0.05]; the association with sCD14 diminished in significance [RR (95%CI) 2.0 (0.77 – 5.25), p=0.16].

Poster Abstracts

Figure. Kaplan-Meier survival estimates of HIV-infected persons initiating ARV in multi-national settings and their rate of developing clinical failures in persons with high (>Q3) compared to low ( ≤ Q3) inflammatory marker levels.

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CROI 2015