CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

Methods: People living with HIV (PLWH) who had switched to a 2DR since 2018 were enrolled in this retrospective cohort, provided they had discontinued ≥1 anti-HBV drug and that their anti-HBV core (HBc) status was known. Rates of liver function test increase (LFTI) above the upper limit of normality were determined using Kaplan-Meier estimates and compared between those with and without OHBVI. Cox regression, adjusting for potential confounders, and random-effects linear regression with repeated measures were also used. All analyses were conducted separately according to the type of 2DR used (including 3TC or without any active HBV-agents). Results: 162 patients switched to a 2DR containing 3TC while 105 to a regimen without 3TC and TFV. Their characteristics are shown in Fig 1. Among those on 3TC, incidence of LFTI was 13.3 and 16.8 per 100 person-years in those with and without OHBVI, respectively (IRR 0.79; 95%CI 0.36-1.64; p=0.514). Uni and multivariable Cox regression showed no significant association between OHBVI and LFTI (HR 0.8; 95%CI 0.4-1.6; p=0.583), after adjusting for possible confounders. No association between ALT levels and OHBVI was observed using a random-effects linear regression, adjusted for time and baseline ALT (coeff -0.39;95%CI -2.3-1.5). Among those with no anti-HBV agents in the regimen, LFTI rates were 13.9 and 13.9 per 100 patient-years in those with and without OHBVI, respectively (IRR 0.99; 95% CI 0.31-3; p=0.998). Using Cox regression, no significant association between OHBVI and LFTI was found (HR 1.33, p=0.568). Adjusted models for potential confounders yielded similar findings. Similarly, OHBVI was not significantly associated to ALT levels at linear regression analysis (coeff -0.87; 95%CI -3.8-2.1). No clinical HBV reactivations nor acute infections were observed. Conclusion: Presence of OHBVI infection was not significantly associated with transaminase elevation among PLWH treated with 2DR lacking anti-HBV agents. This real-life observation provides reassurance regarding the safety of Hepatitis B Reactivation in PLWH With Anti-Core Antibody After Switch to an Anti-HBV Sparing Regimen Giulia Morsica 1 , Riccardo Lolatto 1 , Sara Diotallevi 1 , Valentina Svicher 2 , Costanza Bertoni 3 , Alessia Siribelli 3 , Hamid Hasson 1 , Sabrina Bagaglio 1 , Tommaso Clemente 3 , Arianna Forniti 4 , Romina Salpini 2 , Caterina Uberti-Foppa 3 , Antonella Castagna 3 , Nicola Gianotti 1 1 San Raffaele Scientific Institute, Milan, Italy, 2 University of Rome Tor Vergata, Rome, Italy, 3 Vita Salute San Raffaele University, Milan, Italy, 4 University of Florence, Florence, Italy Background: Anticore antibody (antiHBc) in absence of hepatitis B surface antigen (HBsAg) is defined as an isolated antiHBc status that may be associated with HBV reactivation. We decided to investigate HBV reactivation in antiHBc PLWH (with isolated anti-HBc or with anti-HBc and anti-HBsAg) after the switch from ART including drugs active on both viruses (tenofovir disoproxil fumarate, TDF and tenofovir alafenamide, TAF) to an antiHBV sparing regimen (antiHBVsr) because in PLWH the loss of HBsAg with or without anti-HBsAg seroconversion is probably consequent to ART treatment including drugs active on both viruses (HIV/HBV) rather than past HBV infection. Additionally, HBV reactivation has been described in immunocompromised anti-HBsAg positive people. Methods: HBV reactivation in antiHBc-PLWH was assessed by an alteration of alanine aminotransferase (ALT) above the upper limit of the normal range after the switch to antiHBVsr dolutegravir/rilpivirine (DOL/RPV) or long acting therapy cabotegravir/rilpivirine (CAB/RPVLA). Forty-one individuals with antiHBc and at least 2 ALT values available after the switch to antiHBVsr: (DOL/ RPV, (number, N=15), CAB/RPVLA(N=26) were evaluated. Data were collected as part of routine clinical care and recorded into the database of the Division of Infectious Diseases of the San Raffaele Hospital (CSLHIV Cohort). Data freezing was 29 August 2023. Results: Main characteristics of antiHBc-PLWH at antiHBVsr according to antiHBsAg status (antiHBsAg positive N=34 or negative, N=7) are described in Table 1. All variables analyzed were similarly distributed in the two groups. Overall, the median post-switch follow-up was 8.91 months (interquartile range, IQR 6.78 - 24.14): 8.96 months (IQR 6.78 - 24.14) in anti-HBsAg positive PLWH and 6.97 months (IQR 5.56 - 43.22) in anti-HBsAg negative PLWH, P=0.742. Interestingly, 1/7(14.3%) PLWH with isolated antiHBc showed an increase of ALT (about 20-fold the normal values) about 3 months after switch to CAB/RPVLA, with also appearance of HBV-DNA at high levels (4.8 x107 IU/ mL) and HBsAg seroconversion. He was infected by HBV genotype A that was transitioning to dual therapy in patients with reactive anti-HBc. The figure, table, or graphic for this abstract has been removed.

also identified in plasma sample obtained during HBV chronic infection phase, before any ART treatment. Conclusion: The HBV reactivation is unlikely in antiHBc-PLWH with anti-HBsAg positivity after switch to anti-HBVsr, while close monitoring of ALT and possibly HBV-DNA in PLWH with antiHBc alone, after switch to anti-HBVsr is necessary.

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Circulating HBsAg-Specific B-Cells Are Partially Rescued After Achieving Functional Cure Shuqin Gu 1 , Libo Tang 2 , Guofu Ye 2 , Ling Guo 3 , Shihong Zhong 2 , Xiaoyi Li 2 , Nikolai Novikov 4 , Simon P. Fletcher 4 , Sarah Valencia 1 , M. Anthony Moody 1 , Yongyin Li 2 1 Duke Human Vaccine Institute, Durham, NC, USA, 2 Southern Medical University Nanfang Hospital, Guangzhou, China, 3 Southern Medical University Nanfang Hospital, Guangzhou, Guangdong, China, 4 Gilead Sciences, Inc, Foster City, CA, USA Background: Hepatitis B surface antigen (HBsAg) loss defines a functional cure for chronic hepatitis B infection. Herein, we aimed to characterize circulating HBsAg-specific B cells and identify B-cell epitopes directly associated with HBsAg loss. Methods: Seventy-eight treatment-naïve patients with chronic HBV infection were classified into 4 groups according to the EASL guidelines (2017): hepatitis B e antigen (HBeAg) negative chronic infection (n=21), HBeAg-positive chronic infection (n=20), HBeAg-negative chronic hepatitis (n=17), and HBeAg-positive chronic hepatitis (n=20). Forty-six patients who achieved HBsAg loss (n=24) or seroconversion (n=22) following antiviral treatment and 16 hepatitis B vaccinees with normal alanine aminotransferase levels were enrolled. HBsAg specific B cells phenotypes and function were analyzed by flow cytometry. ELISpot assay was used to measure the ability of B cells to secrete antibodies. HBsAg specific B-cell epitopes associated with functional cure were mapped by ELISA. Results: The classical resting memory B cell population (RM, CD21+CD27+) in HBsAg-specific B cells was reduced while the proportion of atypical memory B cells (AtM, CD21-CD27-), a functionally exhausted subset, was expanded in chronically HBV-infected patients. An increased proportion of RM B cells and a deceased proportion of AtM B cells were observed in patients after achieving functional cure. There was no correlation between total HBsAg-specific B cells and virological parameters, but we found an inverse correlation between HBsAg levels and HBsAg-specific RM B-cell frequency. Moreover, HBsAg-specific B cells expressed lower levels of CD32 and higher levels of IL-6 upon stimulation in patients with HBsAg loss. Intriguingly, the frequency of HBsAb-secreting B cells was significantly increased after achieving functional cure. Sera from patients with HBsAg loss mainly reacted with peptides S60, S61, and S76, suggesting that they are dominant linear B-cell epitopes relevant for functional cure. Notably, an expansion of HBsAg-specific B cell was detected in S76-reactive subjects, accompanied by lower PD-1 expression. Conclusion: HBsAg-specific B cells were partially restored in patients after achieving functional cure. Functional cure-related epitopes are promising targets of therapeutic vaccine development for chronic HBV infection to increase the functional cure rate. Monthslong HBV Suppression by TFV Double Ester Prodrugs Srijanee Das , Weimin Wang, Samiksha Raut, Murali Ganesan, Grace A. Bybee, Nam Thai Hoang Le, Howard E. Gendelman, Natalia A. Osna, Larisa Poluektova, Benson Edagwa University of Nebraska Medical Center, Omaha, NE, USA Background: Tenofovir (TFV) prodrugs [TFV disoproxil-/TFV alafenamide- fumarates (TDF/TAF)] are recommended daily oral treatments for chronic hepatitis B (HBV) infection. Given the growing popularity of long-acting (LA)

Poster Abstracts

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CROI 2024 218