CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

303

Factors Associated With Detectable Viral Load Among PLHIV in Serodiscordant Partnerships in Tanzania Abbas Ismail 1 , Damian Damian 1 , Emilian Karugendo 2 , Fahima Issa 3 , Deogratias Kakiziba 4 , Ahmed Khatib 5 , Lilian S. Shija 1 , Rebecca Laws 6 , George S. Mgomella 1 , Alexander Kailembo 1 , Mahesh Swaminathan 1 , Sarah Porter 1 1 US Centers for Disease Control and Prevention Dar es Salaam, Dar es Salaam, Tanzania, 2 National Bureau for Statistics (NBS), Dodoma, Tanzania, 3 Office of Chief Government Statistician (OCGS), Zanzibar, Tanzania, 4 ICAP at Columbia University in Tanzania, Dar es Salaam, Tanzania, 5 Zanzibar AIDS Commission (ZAC), Zanzibar, Tanzania, 6 Centers for Disease Control and Prevention, Atlanta, GA, USA Background: People living with HIV (PLHIV) with undetectable HIV viral load (VL) cannot sexually transmit HIV to others. Forthcoming clinical guidelines in Tanzania define full HIV VL suppression as <50 copies/mL. PLHIV with detectable VL (DVL) in serodiscordant (SD) marriages or cohabiting relationships (SD-PLHIV) are at increased risk of transmitting HIV to their partner without HIV. Using data from a Tanzania population-based survey, we report prevalence of, and factors associated with DVL among SD-PLHIV. Methods: The Tanzania HIV Impact Survey (THIS) 2022-2023, completed March 2023, is a nationally representative, cross-sectional household survey. Consenting participants aged ≥15 years responded to a questionnaire including items on relationship status, sociodemographic data, and HIV risk behaviors, and were offered household HIV testing. HIV VL was measured for PLHIV. We defined DVL as HIV VL ≥50 copies/mL, and we defined SD-PLHIV as a participant with a positive THIS HIV test result, and whose most recent sexual partner had a recorded negative THIS HIV test result; and among those whose marital status was defined as married or cohabiting with a partner. Binary logistic regression accounting for complex survey design and sampling weights was used to assess prevalence and correlates of DVL among SD-PLHIV. Results are reported as weighted estimates (%) and adjusted odds ratios (aOR) with 95% confidence internals (CI). Results: Among 1,850 PLHIV identified in THIS, 51.6% (48.6-54.7%) were married or cohabiting. Of those, 61.4% (57.0-65.5%) had a recent sexual partner with a recorded THIS HIV test result, and 46.1% (39.7-52.7%) of those partners had a negative HIV test result. Of 261 SD-PLHIV analyzed, median age was 39 years (interquartile range: 31-48), and 51.3% (42.9-59.5%) were female. Overall, 42.8% (35.2-50.9%) of SD-PLHIV had DVL (Table). Prevalence of DVL decreased by age). Sex, education, and residence were not associated with DVL. Conclusions: We observed high prevalence of DVL among SD-PLHIV in our analysis. Programs focused on improving awareness of HIV prevention interventions for serodiscordant married or cohabiting partners and tailored interventions focusing on PLHIV 15-34 years might improve HIV viral load suppression among SD-PLHIV.

attachment inhibitor and is thought to stabilize a native state of HIV Env, the state recognized by most broadly neutralizing antibodies, while also influencing Env glycosylation and proteolytic cleavage. However, the precise mechanism(s) by which TMR affects Env processing and conformation, particularly on cell associated versus virus-incorporated forms of Env, remains unclear. Methods: In this study, we measured the impact of FTR on antibody binding to Env using a cell-based assay in two systems: a tetherin-high system presenting Env on virus particles and a tetherin-low system presenting cell-surface Env. Using this system, we examined binding with and without TMR across various HIV-1 Env forms, including lab-adapted and primary strains, using several bNAbs targeting CD4, V2, and V3 regions. Additionally, we assessed bNAb binding to wildtype, hypercleavable (RR), and uncleaved (RS) Env mutants of QH0692 HIV-1 T/F strain over time. Results: TMR increased V3 region recognition of bnAbs for wildtype viruses (YU2, T/F QH0692), with more pronounced effects on cell-associated (CA) versus virus-incorporated (VI) forms of Env. For the uncleavable Env QH0692 RS mutant an overall reduction of bnAbs binding was observed, whereas bnAb binding specifically to the V3 region, was dramatically enhanced. While this effect was observed for CA and VI forms of Env, enhancement was more marked on CA forms, suggesting a more pronounced effect on cell-associated forms of gp160 Env. Additionally, enhancement of V3 directed bnAb binding after 15 mins of TMR treatment with the RS mutant (gp160), suggests that TMR may directly influence Env conformation rather than indirectly affecting it through processing or glycosylation inhibition. Conclusions: These data indicate that FTR does not primarily affect all strains by decreasing Env expression, and may be used in combination with certain V3 bnAb treatments to potentially enhance the effectiveness of bnAb-based therapies. CXCR4-Using HIV-1 Variants Evolve in the Presence of and Co-Exist With CCR5-Using Variants Shuntai Zhou 1 , Nathan Long 1 , Ean Spielvogel 1 , Michelle Floris-Moore 1 , Catalina Ramirez 1 , Andrew Edmonds 1 , Yijia Li 2 , Ighovwerha Ofotokun 3 , Seble Kassaye 4 , Kathryn Anastos 5 , Margaret Fischl 6 , Stephen Gange 7 , Christina Ochsenbauer 8 , Alan Landay 9 , Jack Dehovitz 10 1 University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, 2 University of Pittsburgh, Pittsburgh, PA, USA, 3 Emory University, Atlanta, GA, USA, 4 Georgetown University, Washington, DC, USA, 5 Albert Einstein College of Medicine, Bronx, NY, USA, 6 University of Miami, Miami, FL, USA, 7 The Johns Hopkins University, Baltimore, MD, USA, 8 University of Alabama at Birmingham, Birmingham, AL, USA, 9 University of Texas Medical Branch, Galveston, TX, USA, 10 State University of New York Downstate Medical Center, Brooklyn, NY, USA Background: HIV-1 uses either CCR5 (R5 virus) or CXCR4 (X4 virus) as a coreceptor to enter host cells. X4 variants, usually seen in the late stage of infection, are associated with more rapid disease progression. However, the triggering event that allows the evolution of X4 variants and the dynamics of X4 and R5 variants following the emergence of X4 variants are unclear. Methods: We identified 21 women with HIV in the Women’s Interagency HIV Study (WIHS) whose: 1) CD4 T+ cell counts declined from >600 to <100 cells/ µl in the absent of effective antiviral therapy while in the study, and 2) plasma samples were available during the period of CD4+ T cell decline with HIV-1 RNA quantification. Multiplexed Primer ID NGS targeted HIV-1 gag , pol and env (V1/V3) of longitudinal specimens collected every 6 months. X4 variants were inferred using the Geno2Pheno coreceptor algorithm; X4 lineages were defined as having a false positive rate below 2% and comprising at least 0.3% of the intra-host viral population. Results: A median of 4 years follow-up were studied for each participant. X4 variants were identified in 16 participants, with a median CD4+ T cell level of 620 cells/µL at the time of detection. At the time point when X4 first emerged, these variants constituted a median of 11% of the intra-host population. X4 variants co-existed with the R5 variants in longitudinal follow-up. At the final time point, the X4 population made up a median of 19% of the intra-host quasispecies. The emergence of X4 variants accelerated disease progression, evidenced by an increased CD4+ T cell decline rate of 206 cells/ µl/year (95% CI: 31 to 382, p =0.025) following their emergence. The X4 Env V3 sequences were linked with specific Env V1/V2 lineages, suggesting genetic compartmentalization of X4 variants. In some participants, multiple X4 lineages with distinct V3 sequences were identified at the same time point, suggesting diverse origins of X4 variants. X4 and R5 variants continued to evolve over time. The emergence of X4 did not increase the viral diversity in Env V1/V3.

Poster Abstracts

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Enhanced Recognition of V3 bNAb Epitopes Induced by Fostemsavir on Cell-Associated Primary HIV-1 Env Raymond A. Alvarez, Eric Acosta, Svenja Weiss, Dania Figueroa Acosta, Benjamin Chen Icahn School of Medicine at Mount Sinai, New York, NY, USA Background: Fostemsavir (FTR), approved by the FDA in July 2020, is a first-in-class small molecule for treating multi-drug resistant HIV-1 infection. It is the prodrug of its active form, temsavir (TMR). TMR is classified as an

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CROI 2025