CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

Conclusion: At Year 2, B/F/TAF was associated with significantly higher rates of HBeAg loss/seroconversion and numerically higher rates of HBsAg loss/ seroconversion and ALT normalization compared with DTG+F/TDF in people with HIV-1/HBV. This analysis suggests that the treatment difference of TAF- vs. TDF-based therapy for some or all HBV treatment outcomes may be greater for certain subgroups, such as people <30 years of age, or with baseline HBV DNA <8 log 10 IU/mL, HBV genotype B/C or baseline ALT levels above normal.

quantity of granulocytic MDSCs (gMDSCs) in the human liver was analyzed by immunofluorescence assay. Wild-type C57BL/6 mice were used to establish a hydrodynamic injection HBV mice model. Results: The frequency of circulating MDSCs in patients infected with chronic HBV was higher than that in the HC group. The circulating MDSCs frequency was negatively correlated with the serum levels of ALT and AST. The number of CD15 and CD66b double-positive cells indicating gMDSCs in CHB patients was higher than that in IT and IC patients. Exogenous IL-21 promoted MDSCs differentiation into M2-like macrophages while also increasing their expression of Arginase I. IL-21 also enhanced the suppressive activity of MDSCs in inhibiting the expression of IFN-γ in T cells. Hydrodynamic injection HBV mice model injected with IL-21 plasmid showed lower ALT concentration and higher production of Arginase I in MDSCs than mice injected with blank plasmid. Conclusion: Our study highlights the robust immune-suppressive activity of MDSCs, which can be enhanced by exogenous IL-21, and their potential role in protecting against liver inflammation in chronic HBV infection. These findings provide a novel perspective on the involvement of IL-21 in the negative regulation of intrahepatic inflammation and have implications for the development of immunotherapeutic strategies to optimize the available anti inflammatory hepatinica in chronic HBV infection. Factors Associated With HBV Response to B/F/TAF vs DTG + F/TDF at W96 in People With HIV-1 and HBV Anchalee Avihingsanon 1 , Hongzhou Lu 2 , Chee Loon Leong 3 , Chien-Ching Hung 4 , Sasisopin Kiertiburanakul 5 , Man-Po Lee 6 , Khuanchai Supparatpinyo 7 , Fujie Zhang 8 , Jason Hindman 9 , Hongyuan Wang 9 , Hui Liu 9 , Taisheng Li 10 1 HIV-NAT, Bangkok, Thailand, 2 Shanghai Public Health Clinical Center, Shanghai, China, 3 Hospital Kuala Lumpur, Kuala Lumpur, Malaysia, 4 National Taiwan University Hospital, Yunlin, Taiwan, 5 Mahidol University, Bangkok, Thailand, 6 Queen Elizabeth Hospital, Hong Kong, Hong Kong, 7 Chiang Mai University, Chiang Mai, Thailand, 8 Beijing Ditan Hospital, Beijing, China, 9 Gilead Sciences, Inc, Foster City, CA, USA, 10 Peking Union Medical College Hospital, Beijing, China Background: The Phase 3 ALLIANCE study investigated the efficacy and safety of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) vs. dolutegravir + emtricitabine/tenofovir disoproxil fumarate (DTG+F/TDF) in people initiating therapy for HIV-1 and HBV. Over 96 weeks (W), B/F/TAF showed significantly higher rates of HBeAg loss/seroconversion, and numerically higher rates of HBsAg loss/seroconversion and ALT normalization, vs. DTG+F/TDF. Overall, rates of HBeAg and HBsAg loss/seroconversion and ALT normalization at W96 were substantially higher in ALLIANCE than in TDF or TAF studies for HBV monoinfection, especially with B/F/TAF, but the mechanism behind this difference is unclear. Here, we explore factors associated with HBV treatment response with B/F/TAF vs. DTG+F/TDF through W96. Methods: Adults with HIV-1/HBV from 46 sites internationally (N=243) were randomized 1:1 to B/F/TAF or DTG+F/TDF plus corresponding placebos. This subgroup analysis compares the percentages of participants with HBe/sAg loss/ seroconversion or ALT normalization with B/F/TAF vs. DTG+F/TDF at W96 (Year 2) according to baseline demographics, HBV genotype, and markers of HIV-1/ HBV disease severity. Results: There were significantly higher rates of HBeAg loss and seroconversion with B/F/TAF vs. DTG+F/TDF in participants who were <30 years of age, or with baseline HBV DNA <8 log 10 IU/mL, HBV genotype B/C, or baseline ALT levels above normal (Table), and in those who were Asian, or with ≥95% study drug adherence, baseline HIV-1 RNA ≤100,000 c/mL, baseline CD4 ≥200 cells/µl, or asymptomatic HIV-1 (HBeAg loss only) at baseline. There were also significantly higher rates with B/F/TAF vs DTG+F/TDF for: HBsAg loss/seroconversion in participants with HBV genotype B/C; HBsAg loss and ALT normalization in those with baseline HBV DNA <8 log 10 IU/mL; HBsAg loss in those who were Asian or who had ≥95% study drug adherence; ALT normalization in those who were HBeAg negative at baseline.

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Novel Biomarkers as Determinants of HBsAg Loss in Persons With HIV/ HBV on Tenofovir Lorin Begré 1 , Anders Boyd 2 , Marie-Laure Plissonnier 3 , Barbara Testoni 3 , Charles Béguelin 1 , Franziska Suter-Riniker 4 , Caroline Scholtes 3 , Juergen K. Rockstroh 5 , Karine Lacombe 6 , Lars Peters 7 , Massimo Levrero 3 , Andri Rauch 1 , Fabien Zoulim 3 , Gilles Wandeler 1 1 University Hospital of Bern, Bern, Switzerland, 2 Public Health Service Amsterdam, Amsterdam, Netherlands, 3 L’Université Claude Bernard Lyon 1 , Lyon, France, 4 University of Bern, Bern, Switzerland, 5 Bonn University Hospital, Bonn, Germany, 6 Assistance Publique–Hôpitaux de Paris, Paris, France, 7 University of Copenhagen, Copenhagen, Denmark Background: HBsAg loss is associated with improved clinical outcomes in persons with hepatitis B virus (HBV) infection. The association between novel biomarkers, including circulating HBV RNA and hepatitis B core-related antigen (HBcrAg), and this outcome has not been studied in persons with HIV/HBV. We aimed to evaluate rates of HBsAg loss and associated risk factors in Euro-B, a multi-cohort collaboration including participants from the Swiss HIV Cohort Study and EuroSIDA. Methods: We included participants with a positive HBsAg and ≥6 months of follow-up on tenofovir-containing antiretroviral therapy (ART), who had quantitative HBsAg (qHBsAg), HBV DNA, HBcrAg and HBV RNA measured at tenofovir start. We evaluated rates of HBsAg loss, defined as a negative qualitative test or qHBsAg <0.05 IU/mL, after 2 years of tenofovir therapy and at the last follow-up visit. We assessed risk factors for HBsAg loss on tenofovir overall and in HBeAg-stratified analyses using multivariable logistic regression. Due to collinearity between HBcrAg and HBV RNA, we evaluated risk factors in two separate multivariable logistic regression models. Results: Of 304 participants included, 23.0% experienced HBsAg loss during a median follow-up time of 11 years (IQR 6-15). After two years, 37/265 (14.0%) participants had experienced HBsAg loss. At tenofovir start, median age was 41 years (IQR 36-46), 61/304 (20.1%) were female at birth, 152/304 (50.0%) were ART-naïve, median CD4 count was 325 cells/mm 3 (IQR 210-482), and 109/233 (46.8%) were HBeAg positive. At tenofovir start, 72/304 (23.7%) participants had a qHBsAg <1000 IU/mL, 79/304 (26.0%) had HBV DNA <20 IU/ mL, 72/304 (23.7%) had HBcrAg ≤3 log 10 U/mL and 140/304 (46.1%) had HBV RNA <10 copies/mL. In both models, only qHBsAg <1000 IU/mL at baseline was associated with HBsAg loss (model with HBcrAg: OR 12.6, 95% CI 5.4-29.5; model with HBV RNA: OR 9.6, 95% CI 4.3-21.4). In HBeAg-positive participants, HBV RNA (OR 0.5 for 1 log 10 increase, 95% CI 0.3-0.8) was associated with HBsAg loss. In HBeAg-negative participants, only qHBsAg <1000 IU/mL (OR 10.8, 95% CI 3.1-36.9) was associated with this outcome. Conclusion: We found high rates of HBsAg loss among persons with HIV/HBV, with 14% of events occurring during the first two years of treatment. Baseline qHBsAg levels were strongly associated with HBsAg loss in HBeAg-negative participants, whereas HBV RNA may be an independent predictor of HBsAg loss in HBeAg-positive persons with HIV/HBV.

Poster Abstracts

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CROI 2024 216