CROI 2024 Abstract eBook

Abstract eBook

Oral Abstracts

164

Provisional Results From a 3-month Clofazimine/Rifapentine Containing Regimen for Drug-Sensitive TB John Metcalfe 1 , Isabelle Weir 2 , Kimberly K. Scarsi 3 , Samuel Pierre 4 , Austin Van Grack 5 , Cecilia Kanyama 6 , Maxwell Yohane 7 , Wadzanai Samaneka 8 , Neetal Nevrekar 9 , Jorge Leon-Cruz 2 , Alberto Mendoza- Ticona 10 , Melanie Goth 11 , Richard E. Chaisson 12 , for the ACTG A5362 CLO-FAST Study Team 1 University of California San Francisco, San Francisco, CA, USA, 2 Harvard TH Chan School of Public Health, Boston, MA, USA, 3 University of Nebraska Medical Center, Omaha, NE, USA, 4 GHESKIO, Port au-Prince, Haiti, 5 DLH Corporation, Bethesda, MD, USA, 6 University of North Carolina Project–Malawi, Lilongwe, Malawi, 7 Kamuzu University of Health Sciences-Johns Hopkins Research Project, Blantyre, Malawi, 8 University of Zimbabwe, Harare, Zimbabwe, 9 The Johns Hopkins University Baltimore-India Clinical Trials Unit, Pune, India, 10 Socios en Salud Sucursal Peru CRS, Lima, Peru, 11 National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA, 12 The Johns Hopkins University School of Medicine, Baltimore, MD, USA Background: Clo-Fast (ACTG A5362; NCT04311502) is a randomized, controlled, open-label phase IIc clinical trial evaluating the safety and efficacy of a 3-month rifapentine (P1200mg)/clofazimine (CFZ)- containing regimen versus 6-month standard of care (SOC) for drug-susceptible (DS) TB that stopped enrollment early due to lack of clinical efficacy. We present results from data through Sept 25, 2023, when the last participant completed study treatment. Methods: Adults enrolled at six sites in Malawi, Zimbabwe, South Africa, India, and Haiti. Randomization, stratified on HIV status and advanced disease on chest X-ray, was to: Arm 1 (13-week experimental regimen): 3PHZEC; Arm 2 (26-week SOC): 2RHZE/4RH; or Arm C (PK subgroup without CFZ load, then SOC): 1PHZEC/1RHZE/4RH. The primary outcomes were (efficacy) time to stable liquid culture conversion through week 12 and (safety) proportion experiencing an AE ≥ grade 3 through week 65 in Arms 1 and 2. The proportion with an unfavorable clinical/bacteriologic outcome in Arms 1 and 2 by week 65 was a key secondary outcome. Results: Between June 2021 and April 2023, when the trial was stopped for inefficacy per DSMB recommendation, we enrolled 58 of 110 planned participants to Arm 1, 31 of 55 planned participants to Arm 2, and 15 of 20 planned participants to Arm C. Most participants were male (79%), 29% were living with HIV (median baseline CD4+ 265 cell/mm 3 , IQR 185-379 cell/mm 3 ), 71% had radiographically advanced TB disease, and 25% were 3+ smear positive at entry. Median (IQR) follow-up on study was was 50.2 weeks (39.7, 57.6 weeks). By week 12, 89% (n=48) in Arm 1 and 90% (n=28) of participants in Arm 2 achieved stable culture conversion (adjusted HR 1.17, 90% CI, 0.79 to 1.73, adjusted for baseline HIV status and presence of advanced disease). The cumulative proportion of participants experiencing an AE ≥ grade 3 was higher in Arm 1 (46%) than Arm 2 (16%; difference 30%, 90% CI 14-45%), driven by change in creatinine clearance in Arm 1. The cumulative probability of an unfavorable outcome in Arm 1 was 49% (95% CI 34-67%) versus 34% (95% CI 19-58%) among Arm 2 participants (difference -15%; 95% CI -41% to 11%). The table describes the clinical/bacteriologic unfavorable outcome events. Conclusion: A 13-week regimen containing CFZ and rifapentine was not efficacious for treatment of DS-TB. The SOC arm also had a high rate of unfavorable events, despite high week 12 culture conversion.

165

Association of State-Level PrEP Coverage and State-Level HIV Diagnoses, US, 2012-2021 Patrick S Sullivan , Stephanie Dubose, Kamaria Brisco, Gordon Le, Marta Juhasz Emory University (Atlanta, GA, USA) Background: Pre-exposure prophylaxis (PrEP) is highly effective to reduce risk of HIV infection; the population-level impact of PrEP is predicted to depend on PrEP coverage (e.g., PrEP prescriptions among those with indications), adherence to prescribed PrEP, the extent to which PrEP is used by those at greatest risk for HIV infection, and the extent of viral suppression among community risk contacts. Methods: We used publicly available data on PrEP prescriptions and calculated PrEP coverage per 100 persons with indications in each state during each year. We calculated quintiles of mean PrEP coverage (e.g., proportion of PrEP users among people with an indication for PrEP) during 2012-2021 for 50 US states and the District of Columbia. For each quintile, we calculated the estimated annual percent change (EAPC) in HIV diagnosis rates from 2012-2021 with 95% confidence intervals using temporal trends models and calculated a p value for trend across state-specific quintiles of coverage. Because higher PrEP coverage in a state might be confounded by higher levels of viral suppression, we adjusted EAPC estimates for prior year state-level viral suppression. Results: The estimated state-specific EAPC in HIV diagnosis rates between 2012-2021 ranged from -11.9% (95% CI: -13.0%, -10.8% in Washington, DC) to +10.5% (95% CI: +5.1%, +16.2% in West Virginia). Mean PrEP coverage among states and the District of Columbia between 2012-2021 ranged from 3.8% (West Virginia) to 22.2% (New York). From 2012-2021, the quintile-specific change in HIV diagnosis rates ranged from a 1.7% increase (95% CI: -0.7% to +4.1%) in the lowest quintile of PrEP coverage to an 8.0% decrease (95% CI: -9.3% to -6.8%) in the highest quintile of PrEP coverage, after controlling for yearly changes in viral suppression rates (Figure; p value for trend across quintiles: 0.0077). Conclusion: In an ecologic analysis, increasing PrEP coverage was associated with decreasing new HIV diagnoses from 2012-2021 among US states, even controlling for differences in state-viral suppression. Our data suggest that PrEP coverage is a meaningful measure to assess the progress of PrEP programs. However, our analysis also documented stark differences in the trajectories of PrEP program among US states: there was an 8- fold difference between the extent to which PrEP needs were met between the lowest and highest performing states. PrEP coverage data is useful to monitor progress in state PrEP programs.

Oral Abstracts

42

CROI 2024