CROI 2019 Abstract eBook

Abstract eBook

Poster Abstracts

626 HEPATITIS B VIROLOGIC FAILURE OF TENOFOVIR-BASED THERAPIES IN PATIENTS WITH HIV/HBV Helen L. Zhang 1 , Meredith Mock 1 , Lane R. Bushman 2 , Peter L. Anderson 2 , Andrew J. Muir 1 , Jennifer J. Kiser 2 , Susanna Naggie 1 1 Duke University, Durham, NC, USA, 2 University of Colorado Anschutz Medical Campus, Aurora, CO, USA Background: A subset of patients coinfected with HIV and hepatitis B virus (HBV) exhibits persistent HBV viremia or viral breakthrough despite HIV suppression while on combination antiretroviral therapy (cART) that includes tenofovir (TFV). The current literature supports several etiologies for this phenomenon, most commonly suboptimal cART adherence. In this study, we determined tenofovir-diphosphate (TFV-DP) and emtricitabine-triphosphate (FTC-TP) concentrations in dried blood spots (DBS) as novel measures of cumulative and recent adherence, respectively, among HIV/HBV coinfected patients on TFV. Methods: In this ongoing case-control study, HIV/HBV coinfected adults on a stable tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF)- based cART regimen with 1) HBV breakthrough: HIV viral suppression (<50 copies/mL) for >6 months and prior HBV viral suppression (HBV DNA < lower limit of quantification [LLOQ]) with new HBV DNA >LLOQ or 2) persistent HBV viremia: HIV viral suppression for >24 months and failure to achieve HBV DNA 6 months and HBV viral suppression on most recent assay. A 3mm DBS punch obtained at time of consent was used for analysis. Simultaneous quantification of TFV-DP and FTC-TP levels in DBS were performed using validated liquid chromatography/tandemmass spectrometry methods. Bivariate analysis was performed using Wilcoxon rank-sum test. Results: To date, 6 men (83% Black) with persistent HBV viremia and 9 men (44% Black) with HBV viral suppression have enrolled (Table). Among those on TDF, TFV-DP levels were lower among unsuppressed (n=4) than suppressed (n=5) patients with median (range) levels of 516 (215-1176) and 1456 (1089- 3108) fmol/punch, respectively (p=0.03). Among those on TAF, TFV-DP levels were 84.4 and 428 among unsuppressed patients (n=2) and median (range) of 144 (55.7-279) fmol/punch among suppressed patients (n=4). FTC-TP levels were detectable among 4 of 6 unsuppressed and all suppressed patients. Conclusion: Median TFV-DP in DBS arising from TDF/FTC, reflecting cumulative drug exposure, was nearly 3-fold lower among HBV unsuppressed patients than suppressed patients. In contrast, the majority of both groups had detectable FTC-TP, reflecting recent adherence relative to the clinic visit. Interim findings of this ongoing study support the concern that poor long-term adherence to TFV therapy may underlie the phenomenon of concurrent HBV viremia and HIV viral suppression.

625 HIGH RATES OF HBV FUNCTIONAL CURE AMONG HIV/HBV-COINFECTED PATIENTS ON ART IN ZAMBIA Belinda V. Chihota 1 , Gilles Wandeler 2 , Roma Chilengi 1 , Lloyd Mulenga 3 , Raymond T. Chung 4 , Debika Bhattacharya 5 , Matthias Egger 2 , Michael J. Vinikoor 6 , for the IeDEA Southern Africa 1 Centre for Infectious Disease Research in Zambia, Lusaka, Zambia, 2 Institute of Social and Preventive Medicine, Bern, Switzerland, 3 University Teaching Hospital, Lusaka, Zambia, 4 Harvard Medical School, Boston, MA, USA, 5 University of California San Francisco, San Francisco, CA, USA, 6 University of Alabama at Birmingham, Birmingham, AL, USA Background: Hepatitis B virus (HBV) functional cure, defined as the loss of the hepatitis B surface antigen (HBsAg), is the desired goal of HBV therapy but occurs slowly (~1%/year) in HBV monoinfection. Novel immunomodulatory therapies to augment T-cell responses are under investigation to increase rates of functional cure. In a sentinel cohort of HBV patients with HIV coinfection in Zambia, we investigated the clinical correlates of HBV functional cure during HBV-active antiretroviral (ART). Methods: We enrolled HIV-HBV co-infected adults (≥18 years and HBsAg- positive) at two sites in Lusaka, Zambia, at start of tenofovir disoproxil fumarate-containing ART. At baseline we measured liver function tests, CD4+, and HBV DNA, and yearly thereafter we re-assessed HBV DNA and HBsAg. Negative HBsAg tests were repeated at 6 months along with surface antibody (HBsAb). After excluding those with <1 year follow-up, we analysed the proportion with HBsAg loss on ART and explored possible predictors including age, sex, baseline CD4+ categories (<200, 200-350, and >350 cells/mm³), HBV DNA (undetectable [<20], 20-20,000, and >20,000 IU/ml), baseline ALT elevation, and 1-year change in CD4+. Logistic regression and Cuzick’s non- parametric test for trend were used in statistical analyses. Results: Among 267 patients analysed, median age was 34 years (interquartile range [IQR], 27-45), 102 (38.2%) were women, and median baseline CD4+ count was 204 cells/mm³ (IQR, 99-341). During a median of 2.1 years on ART, 34 (12.7%) became HBsAg-negative. Most events (n=22) occurred in the initial year of therapy, 93.5%were confirmed with further testing, and 57.1%with HBsAg loss had detectable surface antibodies (HBsAb). With CD4+<200 at ART start there was a trend towards increased HBsAg loss compared to CD4+>350 cells/ mm3 (P=0.155), but we did not find an association with age, sex, ALT elevation, or CD4+ change. Patients with either baseline undetectable or DNA >20,000 had increased HBsAg loss compared to moderate HBV VL (20-20,000 IU/ml; P<0.01; Figure 1). Conclusion: A high proportion of HIV-HBV patients in Zambia experienced HBV functional cure on ART relative to what occurs in HBV monoinfection. Robust ART-induced immune reconstitution in the setting of high HBV antigen load may enhance anti-HBV immune responses in the liver. A better understanding of this mechanism could inform immunomodulatory therapies to increase HBV functional cure.

Poster Abstracts

CROI 2019 237