CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

Conclusions: By maintaining the control over viral reservoir and microbial translocation, 12-month switch to INSTI-based dual cART contribute to T-cell activation containment, and yet fails to revert cellular stress as measured by circulating mitochondrial DNA. The effects of longer 2DR to contain the enduring HIV-driven cell stress needs further investigation. The figure, table, or graphic for this abstract has been removed. ALLIANCE OLE: Switch to B/F/TAF in People With Both HIV-1 and HBV Anchalee Avihingsanon 1 , Chee Loon Leong 2 , Chien-Ching Hung 3 , Sasisopin Kiertiburanakul 4 , Man-Po Lee 5 , Khuanchai Supparatpinyo 6 , Sharline Madera 7 , Hongyuan Wang 7 , Jason T. Hindman 7 , Taisheng Li 8 1 HIV-NAT, Thai Red Cross AIDS and Infectious Disease Research Centre, Bangkok, Thailand, 2 Hospital Kuala Lumpur, Kuala Lumpur, Malaysia, 3 National Taiwan General Hospital Yunlin, Yunlin, Taiwan, 4 Mahidol University, Bangkok, Thailand, 5 Queen Elizabeth Hospital, Hong Kong, Hong Kong, 6 Chiang Mai University, Chiang Mai, Thailand, 7 Gilead Sciences, Inc, Foster City, CA, USA, 8 Peking Union Medical College Hospital, Beijing, China Background: In treatment-naïve adults with HIV-1 and hepatitis B virus (HBV) co-infection, the ALLIANCE study showed that bictegravir/emtricitabine/ tenofovir alafenamide (B/F/TAF) was noninferior for HIV-1 RNA suppression and superior for HBV DNA suppression compared to dolutegravir + emtricitabine/ tenofovir disoproxil fumarate (DTG+F/TDF) at Week [W] 48. Suppression rates were maintained through W96, after which DTG+F/TDF participants switched to B/F/TAF for an additional 48W of open-label extension (OLE). Here, we report efficacy and safety of those who switched. Methods: ALLIANCE (NCT03547908) was a randomized, double-blind, active-controlled Phase 3 study of B/F/TAF vs DTG+F/TDF in adults with HIV-1 and HBV. This analysis presents data from OLE baseline (BL) through OLE W48 for participants who switched to B/F/TAF from DTG+F/TDF after the 96W randomized phase. We report: OLE BL demographics/characteristics; HIV-1 RNA <50 copies (c)/mL, HBV DNA <29 IU/mL, HBV e-antigen/surface antigen (HBeAg/HBsAg) loss/seroconversion, alanine aminotransferase (ALT) normalization per 2018 American Association for the Study of Liver Diseases (AASLD) criteria at OLE W48 (missing=excluded [M=E]); and study drug– related treatment-emergent adverse events (TEAEs) up to OLE W48. Results: At OLE BL (N=89), 97.8% of participants were male at birth, 94.4% were Asian, median (range) age was 34 (22-61) years, 30.3% had ALT levels above the upper limit of normal (ULN), 58.4% were HBeAg positive, 96.6% had HIV-1 RNA <50 c/mL, and 83.1% had HBV DNA <29 IU/mL. In total, 88 participants (98.9%) who switched to B/F/TAF completed 48 W of OLE. At OLE W48, 95.4% had HIV-1 RNA <50 c/mL and 86.6% had HBV DNA <29 IU/mL ( Table ). HBeAg loss/seroconversion was 17.0%/12.8%; HBsAg loss/ seroconversion was 4.3%/0%; ALT normalization was 52% ( Table ). Up to OLE W48, 17 (19.1%) participants experienced a study drug-related TEAE (none serious), of which 3 (3.4%) were Grade 3 or 4; no participants experienced a TEAE that led to discontinuation and none died. Conclusions: B/F/TAF maintained high rates of HIV-1 and HBV viral suppression following switch from DTG+F/TDF, with further improvements in key clinical outcomes including HBeAg loss/seroconversion, HBsAg loss, and ALT normalization through 48W of open-label B/F/TAF treatment. Overall, B/F/TAF was well tolerated, with no study drug discontinuations due to TEAEs. These results demonstrate the efficacy and safety of B/F/TAF in people with both HIV-1 and HBV who switched from DTG+F/TDF.

of viral reservoirs forms the major obstacle to an HIV cure. HIV reservoirs persist mainly through cellular longevity and proliferation, but replenishment by residual virus replication despite ART has been proposed as a potential mechanism of HIV persistence. In recent years, there has been a clear trend towards ART regimens that include fewer drugs (e.g., dual instead of triple therapy). In this study, we evaluated the possible increase in viral replication and reservoir replenishment in blood and tissue upon ART simplification and the impact of simplification on chronic immune activation and inflammation. Methods: Thirty-six people living with HIV, who received a triple therapy consisting of Dolutegravir (DTG), Abacavir (ABC) and Lamivudine (3TC) and had been fully suppressed for at least 2 years, were enrolled in a phase 3 randomised clinical trial. Half of them were switched to a dual therapy (DTG/3TC). Peripheral blood mononuclear cells (PBMCs), plasma and rectal biopsies were longitudinally collected over 1 year. We quantified total HIV DNA and cell associated unspliced (US) HIV RNA in PBMCs and rectal tissue. Ultrasensitive single-copy HIV RNA assay was performed to determine residual plasma viremia. Expression of immune activation (HLA-DR, CD38) and exhaustion (PD-1, TIGIT) markers and the levels of inflammatory plasma biomarkers including sCD14, IL-6, IL-1β, IL-17α, IFN-γ, and TNF-α were quantified. Results: There were no significant differences in the longitudinal dynamics of total HIV DNA and unspliced HIV RNA in PBMCs between the two groups. In the simplified group, we observed a transient increase in residual viremia at month 9 of the study that returned to baseline by month 12. Similarly, we observed a transient decrease in the CD4/CD8 ratio that returned to baseline by the end of the study. A significant reduction in the percentages of CD4+TIGIT+ T cells and in levels of 5 plasma inflammation markers was also observed. In the control group, we observed a significant decrease in the total HIV DNA in tissue and a significant decrease in CD4+TIGIT+ T cells. Conclusions: Switching to DTG/3TC maintained plasma viral load suppression, didn’t measurably impact HIV persistence markers in blood or tissue, and reduced systemic inflammation. These findings support the use of DTG/3TC in people living with HIV. Effect of 12-Month Switch to Dual cART on T-Cell Homeostasis, Gut and Mitochondrial Damage Valeria Bono, Camilla Tincati, Matteo Augello, Roberta Rovito, Sabrina Marozin, Chiara Orlandi, Anna Casabianca, Giulia Marchetti University of Milan, Milan, Italy Background: Residual immune activation/inflammation is a hallmark of treated HIV. Dual (2DR) regimens are efficacious in maintaining viral suppression, however, their effect on T-cell homeostasis and mitochondrial damage, is ill-defined. Methods: PLWH switching from viro-suppressive, three drug (3DR) cART to an INSTI-based 2DR with sample availability (at switch and approximately 12 months from switch) were studied. We evaluated T-cell surface maturation (CD127/CD45RA) and activation (CD38/CD45RO) by flow cytometry, plasma gut barrier dysfunction (E-cadherin, I-FABP) and microbial translocation (sCD14, LBP, ELISA;16S rDNA, qPCR). In an unselected subgroup of 16 PLWH, we also assessed total intracellular HIV DNA, and circulating cell-free mitochondrial DNA (ccf-mtDNA, qPCR). Wilcoxon test for statistics. Results: We enrolled 60 PLWH (Table1). Switching to 2DR led to significant CD4 increases (32% [27-39] vs 35% [30-40]; p=0.0001), reduction in CD8 (40% [34-45] vs 37% [30-42]; p<0.0001) and rise in CD4/CD8 (0.83 [0.65- 0.91] vs 0.96 [0.76-1.3]; p=0.0007). Moreover, switch to 2DR resulted in a decrease of naïve T cells (CD4/CD45RA: 11% [8-17] vs 10% [6-13], p<0.0001; CD8/CD45RA: 18% [15-22] vs 17% [12-20], p=0.002), and significant expansion of central memory phenotypes (CD4/CD127: 28% [24-33] vs 32% [26-37], p<0.0001; CD8/CD127: 30% [24-34] vs 32% [26-36], p=0.01). We also observed a marked reduction in activation (CD8/CD38: 5% [4-8] vs 3% [2-5], p<0.0001, Fig1A; CD8/CD45RO: 7% [4-11] vs 6 [3-8], p=0.03); CD8/CD38/CD45RO: 1% [0-1] vs 0% [0-1], p<0.0001). No changes in markers of intestinal damage, microbial translocation, bacterial 16S rDNA and total HIV DNA were detected, whereas a significant increase in ccf mtDNA was noted after the switch (Fig.1B). The same trend was observed when the two ccf-mtDNA genes were analysed separately (ND-1 gene: 5,87E+06 cp/ ml [8,52E+05-3,18E+07] vs 2,55E+07 cp/ml [2,75E+06-9,90E+07], p=0.03; D-Loop gene: 6,21E+06 cp/ml [8,75E+05-3,16E+07] vs 2,80E+07 cp/ml [3,46E+06-7,97E+07], p=0.03). No correlations were found between ccf mtDNA and T-cell activation (pre-switch: r=0.02, p=0.9; post-switch: r=0.03, p=0.8).

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