CROI 2020 Abstract eBook

Abstract eBook

Oral Abstracts

Methods: We examined 3 calendar periods: early- (1996-2000), mid- (2001- 2005), and modern- ART (2006-2015). HCC diagnoses were identified and validated through cancer registries or medical records. HBV and HCV infection were confirmed by serologic and/or virologic test and categorized as ever, never infected, or missing. CD4 counts were measured at entry of each calendar period or the beginning of cohort-specific cancer diagnosis ascertainment. HIV RNA viral load (vl) was measured two years before HCC diagnosis or before the end of cancer diagnosis ascertainment. Poisson regression models estimated HCC incidence rates (IR) and rate ratios (aIRR), adjusted for age, sex, race, and viral hepatitis infection. Age-related cumulative incidence of HCC by calendar periods were calculated. Results: Of 109,283 HIV patients with 723,441 person-years (pys) of follow-up, 20%were HCV co-infected, 6% HBV co-infected, 2% triple-infected, 451 developed HCC. PWH who had HBV and/or HCV co-infection were more likely than HIV-monoinfected PWH to develop HCC and did so at earlier ages. From 1996 to 2015, HCC IR increased from 0.28 to 0.75/1000 pys. As compared to HIV- monoinfected persons, PWH co-infected with HBV and/or HCV had substantially greater age-related cumulative incidence of HCC in all 3 periods (Figure). Higher HIV vl (≥500 copies/ml) and lower CD4 counts (≤500 cells/mL) were associated with higher HCC risk (aIRR: 1.8, 95% confidence interval (CI): 1.4-2.4 and aIRR: 1.3, 95% CI: 1.0-1.6, respectively). People who injected drugs had higher HCC risk compared with men who had sex with men (aIRR: 2.0, 95% CI: 1.3-2.9), even after controlling for viral hepatitis co-infection. Conclusion: HCC rates among PWH increased significantly over time. Patients with viral hepatitis co-infection, lower CD4, higher HIV vl, or HIV transmission through injection drug use had higher HCC risk. These findings suggest the importance of HIV viral suppression and treatment of viral hepatitis among PWH in the ART era in order to reduce HCC risk.

plasma HCV RNA levels (r=0.89, 0.88). The median (range) percent change in proportion of infected hepatocytes within the first week was -89.4% (-70.0, -97.7). There were no differences in plasma or liver HCV kinetics between HIV+ and HIV- at baseline or later. Median (range) IP-10 levels at baseline were 369 pg/mL (175, 479) and did not differ significantly by HIV status; however, day 1 and day 14 IP-10 levels were significant higher among HIV+ participants (p<0.05 for both). Conclusion: HIV/HCV co-infected persons have rapid clearance of intrahepatic HCV, similar to HCV mono-infected persons, despite having abundant infection. However, residual immune activation appears to persist despite virologic suppression of both viruses. While this may not have different implications for virologic cures, there may be persistent effects on liver disease progression in HIV/HCV co-infection.

Oral Abstracts

128 CLINICAL PREDICTORS OF LIVER FIBROSIS PRESENCE & PROGRESSION IN HIV-ASSOCIATED NAFLD Lindsay T. Fourman 1 , Takara L.Stanley 1 , Meghan Feldpausch 1 , Julia Purdy 2 , Isabel Zheng 1 , Chelsea S. Pan 1 , Julia Aepfelbacher 2 , Colleen Buckless 1 , Andrew Tsao 1 , Kathleen E. Corey 1 , Raymond T. Chung 1 , Martin Torriani 1 , David E. Kleiner 2 , Colleen Hadigan 2 , Steven K. Grinspoon 1 1 Massachusetts General Hospital, Boston, MA, USA, 2 NIAID, Bethesda, MD, USA Background: Nonalcoholic fatty liver disease (NAFLD) – ranging from steatosis to steatohepatitis to fibrosis – is a major cause of liver disease in HIV. While simple steatosis is regarded as relatively benign, hepatic fibrosis has been linked to all-cause and liver-specific mortality. The natural history of NAFLD in HIV, including which patients are likely to develop clinically overt disease, is not well known. In the current study, we leverage liver biopsy samples from a clinical trial of HIV-associated NAFLD to identify predictors of fibrosis presence and progression. Methods: We recently completed a randomized trial of the growth hormone- releasing hormone analogue tesamorelin to treat NAFLD in HIV. In this study, we found that tesamorelin reduced liver fat and prevented fibrosis progression. Sixty-one participants with HIV and NAFLD were randomized to tesamorelin or placebo for 12 months. NAFLD was defined as hepatic fat fraction (HFF) ≥ 5% by magnetic resonance spectroscopy in the absence of active hepatitis B or C or excess alcohol consumption. Individuals with cirrhosis were excluded. Participants underwent liver biopsy at baseline and 12 months; histologic evaluation was performed by a single expert pathologist blinded to treatment and biopsy order. Results: Among 58 participants with baseline biopsies, 43% had hepatic fibrosis (stage 1, 36%; stage 2, 40%; stage 3, 24%). Fibrosis was associated with greater visceral fat content at baseline (284 ± 91 cm 2 vs. 212 ± 95 cm 2 , P = 0.005), but not subcutaneous fat or BMI. While HFF did not differ between groups, individuals with fibrosis had higher NAFLD Activity Score (3.6 ± 2.0 vs. 2.0 ± 0.8, P < 0.0001), ALT (41 ± 30 U/L vs. 23 ± 8 U/L, P = 0.002), and AST (44 ± 27 U/L vs. 24 ± 10 U/L, P = 0.0003). Among 24 participants randomized to placebo with paired liver biopsies, 38% had progression of fibrosis over 12 months. Higher visceral fat content at baseline (306 ± 119 cm 2 vs. 212 ± 89 cm 2 , P = 0.04) was the only clinical predictor of fibrosis progression, which remained significant upon adjusting for BMI, HFF, and NAS Score. Age, sex, race, duration of HIV, and CD4 count did not relate to fibrosis presence or progression. Conclusion: High rates of liver fibrosis presence and progression were observed in a cohort with HIV and NAFLD. Individuals with greater visceral fat content at baseline were more likely to have baseline fibrosis and progression of fibrosis, suggesting that these patients should be closely monitored and targeted for intervention.

127 HIV/HCV VS HCV: PLASMA AND LIVER VIRAL DYNAMICS AND IP-10 LEVELS Ashwin Balagopal 1 , Jaiprasath Sachithanandham 2 , Julia Leep-Lazar 2 , Jeffrey Quinn 1 , Kenneth Bowden 2 , Kathleen M. Ward 1 , Stephanie Katz 1 , Mark Sulkowski 1 1 Johns Hopkins University School of Medicine, Baltimore, MD, USA, 2 Johns Hopkins University, Baltimore, MD, USA Background: HIV/HCV co-infected people have worse liver disease progression than HCV mono-infected people. Interferon-free therapies have yielded high rates of sustained virologic response after 12 weeks, but shorter therapy has not been uniformly successful in HIV/HCV co-infection. We compared how quickly the liver is cleared of infection with interferon-free therapy in HIV/HCV co-infection and HCV mono-infection. Methods: We enrolled 10 people with chronic genotype 1a HCV infection without cirrhosis in a clinical trial of Sofosbuvir and Velpatasvir for 12 weeks; 5 people had virologically suppressed HIV on antiretrovirals. Participants underwent liver biopsies at baseline and on day 4 or 7 after treatment initiation; single-cell laser capture microdissection was performed to quantify the proportion of infected hepatocytes. Plasma viral kinetics and IP-10 levels were measured over the first two weeks. Results: The median (range) age of participants was 55.5 (28, 66), 5/10 were female, and 8/10 were Black. The median (range) liver stiffness was 6.5 kPa (4.1, 8.6). The median (range) baseline plasma HCV RNA levels was 6.36 log 10 IU/mL (5.68, 7.93). The median (range) proportion of HCV-infected cells was 8% (1%, 87%) at baseline and 1% (<0.3%, 7%) at second biopsy: baseline proportions and the change in proportion of infected cells correlated closely with baseline

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CROI 2020