CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

747

Predictors of HIV Drug Resistance to Dolutegravir in 4 PEPFAR-Supported Countries Juliana D. Da Silva 1 , Sherri Pals 1 , Newton L. Kalata 2 , Nellie Wadonda 2 , Mariama Tejan 1 , Clement Zeh 1 , Maria Liulchuk 3 , Nalia Ismael 4 , Nilesh Bhatt 5 , Gillian Massamha 1 , Christine Watera 6 , Grace Namayanja 7 , Elliot Raizes 1 , for the CADRE Surveillance Network 1 Centers for Disease Control and Prevention, Atlanta, GA, USA, 2 US Centers for Disease Control and Prevention Lilongwe, Lilongwe, Malawi, 3 Center for Public Health of Ukraine, Kyiv, Ukraine, 4 Instituto Nacional de Saúde, Maputo, Mozambique, 5 Elizabeth Glaser Pediatric AIDS Foundation, Washington, DC, USA, 6 Uganda Virus Research Institute, Entebbe, Uganda, 7 US Centers for Disease Control and Prevention Kampala, Kampala, Uganda Background: Dolutegravir-based regimens (DBR) represent >92% of drugs dispensed in PEPFAR-supported programs. Monitoring emergence of and characterizing the risk factors for dolutegravir (DTG) drug resistance (DR) acquisition is a key priority to ensure the continued efficacy and durability of these regimens. We report risk factors for DTG DR identified in a large cohort of patients conducted in four PEPFAR-supported programs. Methods: Adults on a DBR in Malawi, Ukraine, Mozambique, and Uganda whose remnant viral load (VL) samples were successfully genotyped from 2020-2022 were included in the analysis. We defined DTG DR as levels 3-5 (low, intermediate, or high) by Stanford HIV Drug Resistance Database. We fit an exact logistic regression model with DTG DR as the outcome and clinical and sociodemographic variables as covariates. SAS was used to fit the model and produce adjusted odds ratios (aOR) and 95% confidence intervals (CI). Results: A total of 965 specimens were included; 83 had DTG DR. About 9 in 10 individuals were transitioned to DBR from another regimen. Median age was 36.2 years (95%CI 28-43), median time on a DBR was 1.5 years IQR:0.80-2.14), and nearly 60% of individuals in the cohort were female. Male sex [aOR 1.90 (95% CI 1.30, 2.78)]; age 30-39 years [aOR: 2.43 (95%CI 1.41, 4.20)] and 40 to 49 years [aOR: 2.44 (95%CI 1.38, 4.31)]; time on DTG 1-2 years [aOR: 3.09 (95%CI 1.64, 5.82)] and above 2 years [aOR: 3.85 (95%CI 2.02, 7.33)]; VL between 10,000 and 100,000 copies/ml [aOR 1.93 (95%CI 1.13, 3.30)]; any nucleoside reverse transcriptase inhibitor (NRTI) [aOR: 51.6 (95%CI 9.42, 282.2)]; or non- nucleoside reverse transcriptase inhibitor (NNRTI) resistance [aOR: 2.57 (95%CI 1.32, 4.99)] were identified as risk factors to DTG DR. Conclusions: In this multicounty cohort, male sex, ages 30-49 years, VL between 10,000 and 100,000 copies/ml, time on DTG of >1 year and presence of NRTI or NNRTI DR were risk factors for DTG DR. Notably, the duration on DTG showed a dose-response effect, with longer use linked to higher DR rates. The presence of NRTI DR had a large effect that has been previously observed; although NRTI recycling in 2nd-line is supported by data, the presence of NRTI DR may make DTG more vulnerable to DR emergence. In settings where genotypic testing is not widely available, these findings could help programs develop screening algorithms to correctly identify, test and switch those with DR to an effective regimen.

748

Safety and Efficacy of 8 Week Glecaprevir/Pibrentasvir for Acute HCV in People Living with HIV Barbra Cave 1 , Kimberly Workowski 2 , Pablo Ryan 3 , John Smith 4 , Thomas Lutz 5 , Patrick Lank 1 , Linda Fredrick 1 , Anne Welhaven 1 , Dimitri Semizarov 1 , John Marcinak 1 , Joseph S. Doyle 6 1 AbbVie, Inc, North Chicago, IL, USA, 2 Emory University, Atlanta, GA, USA, 3 Hospital Universitario Infanta Leonor, Madrid, Spain, 4 Capital Digestive Care, Norfolk, VA, USA, 5 Infektiologikum, Frankfurt, Germany, 6 Monash University, Melbourne, Australia Background: Globally there are up to 2.3 million people living with HIV (PLHIV) and hepatitis C virus (HCV) co-infection. PLHIV with HCV co-infection are at high risk for liver-related morbidity and mortality. There are currently no approved direct acting antivirals (DAA) for acute HCV infection; however, glecaprevir/pibrentasvir (G/P) has been well studied in chronic HCV infection. Treating acute HCV could reduce onward transmission, accelerating the path to HCV elimination. The objective of this analysis was to examine the efficacy and safety of G/P in PLHIV with acute HCV, and to explore the safety of co administration of HIV therapies with G/P. Methods: M20-350, a phase 3b, multicenter, single-arm, open-label study, evaluated the efficacy and safety of 8-weeks of G/P for acute HCV infection in people who had not previously been treated for the current infection. Efficacy endpoints included the proportion of subjects achieving sustained virologic response 12 weeks after the last dose of G/P (SVR12) evaluated in the intention to-treat (ITT) set (all subjects receiving ≥1 doses of G/P) and the modified ITT (mITT) set (excluding those who did not achieve SVR12 for reasons other than virologic failure). Safety endpoints included changes from baseline in alanine aminotransferase (ALT) and total bilirubin during treatment, treatment emergent (TE) hepatic decompensation, TE serious adverse events (TESAE), and TEAE leading to G/P discontinuation. Exploratory analysis described the concomitant HIV medications taken with G/P. Results: Of 286 subjects, 144 had acute HCV mono-infection and 142 had HIV/acute HCV infection. Table 1 provides demographics and baseline characteristics. The co-infection group SVR12 rate was 97.2% (138/142) in ITT and 100% (138/138) in mITT, with no virologic failures or virologic relapses, and one reinfection (0.7%). All PLHIV and HCV were receiving HIV medication, and 87.3% had HIV-1 RNA <20 copies/mL at baseline. No PLHIV and HCV experienced on-treatment ALT>3x ULN that worsened from baseline, hepatic decompensation, a TESAE that was deemed related to G/P, or a TEAE leading to G/P discontinuation. There were no deaths. The most common HIV treatment contained bictegravir (59/144, 41.0%). No PLHIV had two consecutive HIV-1 RNA levels ≥200 copies/mL while on G/P. Conclusions: An 8-week treatment with G/P was safe and effective in PLHIV with acute HCV infection. Concomitant HIV antiretrovirals maintained HIV suppression and were safe to use with G/P.

Poster Abstracts

749

AA Initiation Among People With HIV and HCV in North America: Factors Driving the Treatment Gap Raynell Lang 1 , Leila Borowsky 2 , Brenna C. Hogan 3 , Elizabeth Humes 4 , Asya Lyass 5 , Arthur Y. Kim 2 , Gregory Kirk 3 , Frank Palella 6 , Michael Silverberg 7 , Edward Cachay 8 , Hyang Nina Kim 9 , Catherine Lesko 4 , Richard Moore 4 , Virginia Triant 2 , Keri N. Althoff 4 , for the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) of IeDEA 1 University of Calgary, Calgary, Canada, 2 Massachusetts General Hospital, Boston, MA, USA, 3 The Johns Hopkins University, Baltimore, MD, USA, 4 The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, 5 Boston University, Boston, MA, USA, 6 Northwestern University, Chicago, IL, USA, 7 Kaiser Permanente Northern California, Oakland, CA, USA, 8 University of California San Diego, La Jolla, CA, USA, 9 University of Washington, Seattle, WA, USA Background: People with HIV (PWH) are at increased risk of coinfection with worse outcomes from hepatitis C virus (HCV) and are a key group targeted for treatment with direct-acting antivirals (DAA). Not all PWH eligible for DAA

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