CROI 2016 Abstract eBook

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Oral Abstracts

150 Hepatitis B and C, Alcohol, and CD4 Drive End-Stage Liver Disease in HIV+ Adults

Keri N. Althoff 1 ; Amy C. Justice 2 ; Joseph J. Eron 3 ; Lisa Jacobson 4 ; Gregory D. Kirk 4 ; Marina B. Klein 5 ;Vincent Lo Re 6 ; Sonia Napravnik 3 ; Michael J. Silverberg 7 ; Richard Moore 4 1 Johns Hopkins Bloomberg Sch of PH, Baltimore, MD, USA; 2 Yale Univ, New Haven, CT, USA; 3 Univ of North Carolina at Chapel Hill, Chapel Hill, NC, USA; 4 Johns Hopkins Univ, Baltimore, MD, USA; 5 McGill Univ Hlth Cntr, Montreal, QC, Canada; 6 Univ of Pennsylvania, Philadelphia, PA, USA; 7 Kaiser Permanente Northern California, Oakland, CA, USA Background: The increased burden of end-stage liver disease (ESLD) in HIV-infected adults is likely driven by both HIV-related and ESLD risk factors. Our objective was to estimate the population attributable fractions (PAF) for hepatitis C (HCV) and B (HBV) infection, at-risk alcohol use, and other ESLD risk factors, interpreted as the proportion of ESLD that could be avoided in HIV-infected adults if all were unexposed to the modifiable risk factor of interest. Methods: We included adults (>=18 years) participating in one of 11 contributing cohorts to the NA-ACCORD with validated ESLD diagnosis from 1 Jan 2000 to 31 Dec 2009 were included. HCV, HBV, smoking, CD4 <200 cells/mm 3 , HIV RNA ≥400 copies/mL, and a past clinical AIDS diagnosis were examined for their relationship with ESLD. HCV and HBV were measured at study entry; all other variables were time-dependent. A sub-group analysis was conducted restricting to participants with alcohol data; at-risk alcohol use was measured at study entry, defined as ≥3 drinks on any day or ≥7 drinks per week for females and ≥4 drinks on any day or ≥14 drinks per week males. Cox proportional hazard models with piecewise constant baseline hazard functions were used to estimate adjusted hazard ratios, which were used to determine adjusted PAFs for the modifiable risk factors of interest. Results: 35,044 adults contributed 134,315 person-years and 387 incident ESLD diagnoses; median follow up was 3.1 years. At baseline, participants who developed ESLD were older, more likely to be male and white, and had greater proportions with HCV, HBV, at-risk alcohol use, smoking, a CD4 <200 cells/mm 3 , and a past AIDS diagnosis compared to those who did not develop ESLD. The PAFs from the primary and sub-group analyses are shown in Figure 1. In the sub-group analysis of 12,158 adults with alcohol data, the PAF for at-risk alcohol use was 33%; there were no substantial differences in PAF estimates for other risk factors. Conclusions: Preventing HCV and HBV could avoid up to 31% and 16% of ESLD in HIV-infected adults, respectively. HCV treatment provision with newly available direct-acting agents may have a notable effect on preventing ESLD in HIV-infected patients. Prevention programs for at-risk alcohol use could avoid up to 33% of ESLD. A quarter of ESLD events may be averted with strong immune function further supporting early and consistent ART use for non-HIV disease prevention.

Oral Abstracts

151 Antiretroviral Therapy Reduces Intrahepatic Hepatitis C in HIV-1/HCV Coinfection Jeffrey Quinn 1 ; Abraham J. Kandathil 1 ; Jennifer Shellenberger 1 ; Ramy El-Diwany 1 ; Merve Gurakar 2 ; Mark Sulkowski 1 ; Ruy M. Ribeiro 3 ; Alan S. Perelson 3 ; David L.Thomas 4 ; Ashwin Balagopal 1 1 Johns Hopkins Univ, Baltimore, MD, USA; 2 Virginia Commonwealth Univ, Richmond, VA, USA; 3 Los Alamos Natl Lab, Los Alamos, NM, USA; 4 Johns Hopkins Univ Sch of Med, Baltimore, MD, USA Background: HIV-1 worsens hepatitis C virus (HCV) replication in co-infected patients, and we and others have recently reported that antiretroviral therapy (ART) initiation reduces plasma HCV RNA levels (Sherman, Sci Trans Med, 2014; Balagopal, Hepatology, 2014). We now test the hypothesis that HIV-1 control with ART decreases intrahepatic HCV replication. Methods: We obtained paired plasma samples and liver biopsies before and >12 weeks after ART initiation in four HIV-1/HCV co-infected persons who had high pre-ART plasma HIV-1 RNA levels. Liver biopsies were snap-frozen in liquid N 2 until processing, then lightly fixed on polyethylene naphthalate membrane slides. Single hepatocytes were isolated by laser capture microdissection as we have done previously (Kandathil, Gastroenterology , 2013); RNA was extracted from each cell separately, and HCV RNA was quantified by realtime PCR and compared to levels of 7sl, an abundant intracellular molecule. Plasma HIV-1 and HCV RNA levels were separately quantified in batch. Results are presented as median (range). Results: The median age was 53.7 (43.7-60.6) years, 1/4 (25%) subjects were female, and 3/4 (75%) were black. The median pre-ART plasma HIV-1 levels and CD4+ T cell count were 5.06 (4.69-5.21) log 10 cp/mL and 246 (203-302) cells/μL, respectively. The median interval between liver biopsies was 196 (168-217) days. CD4+ T cell counts increased by a median (range) of 84 (-35 - 243) cells/μL. HCV RNA levels decreased from a median of 7.06 (6.05-7.29) IU/mL to 6.01 (4.45-6.51) IU/mL. Four hundred separate hepatocytes were laser captured from each liver biopsy, obtained before and after ART, for a total of 2473 separate cells. The proportion of HCV-infected hepatocytes declined from a median of 44.5% (5.7%-55.3%) pre-ART to 16.9% (0.6%-29.7%) after HIV-1 suppression (p<0.05; Figure). Conclusions: In four intensively studied HIV-1/HCV co-infected persons who initiated ART, decreases in plasma HCV RNA levels were associated with a reduction in the proportion of HCV-infected hepatocytes. These results provide rationale for the recommendation to treatment of HIV infection prior to the initiation of HCV therapy in persons with HIV/HCV coinfection.

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CROI 2016