CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

958

Genetics of Plasma Rifapentine Clearance During Pulmonary Tuberculosis Treatment in Study 31/A5349 Ava Y. Xu 1 , Yuki Bradford 2 , Gustavo E. Velásquez 1 , Vincent K. Chang 1 , Marjorie Imperial 3 , Ekaterina V. Kurbatova 4 , Kia Bryant 4 , Phumla Sinxadi 5 , Marylyn Ritchie 2 , John A. Capra 1 , David W. Haas 6 , Radojka M. Savic 1 , for the Tuberculosis Trials Consortium (TBTC) Study 31/ACTG A5349 Study Team 1 University of California San Francisco, San Francisco, CA, USA, 2 University of Pennsylvania, Philadelphia, PA, USA, 3 Gilead Sciences, Inc, Foster City, CA, USA, 4 Centers for Disease Control and Prevention, Atlanta, GA, USA, 5 University of Cape Town, Cape Town, South Africa, 6 Vanderbilt University Medical Center, Nashville, TN, USA Background: Optimizing rifapentine (RPT) dosing is critical for improving tuberculosis (TB) treatment response. Study 31/A5349 (NCT02410772) compared two 4-month RPT-containing regimens — one with and one without moxifloxacin (MFX) — to the standard 6-month regimen. A key determinant of unfavorable TB outcomes in this trial was RPT exposure, with large interindividual variability. We hypothesized that host genetics contributed to variability in clearance (CL) of RPT and its metabolite, 25-O-desacetyl-RPT (des RPT) and evaluated an arylacetamide deacetylase ( AADAC ) variant rs1803155 reported to affect RPT exposure. Methods: Participants received 1200 mg RPT daily, with plasma samples collected for RPT and des-RPT assays between weeks 2 and 8. We imputed genetic variants from low-coverage whole-genome sequence data using GLIMPSE2. Associations with RPT and des-RPT CL were studied genome-wide, adjusting for 8 genetic principal components and NAT2 acetylator status. We assessed the impact of selected variants on RPT CL by pharmacokinetic (PK) modeling using NONMEM. Results: A total of 1094 participants had both PK and genetic data (560 in the RPT/MFX arm, 534 in the RPT arm), with a median age of 30 years (IQR 24, 41) and median weight of 53 kg (IQR 48, 59). There were 29% female, 75% Black, and 12% Asian participants. AADAC rs1803155 was associated with RPT CL in all participants (p=1.1E-11), the RPT/MFX arm (p=1.1E-9), and the RPT arm (p=4.3E-4). The GG genotype was associated with more rapid RPT CL and lower exposure. PK modeling showed that RPT CL increased by 0.266 L/h with AADAC GG and 0.059 L/h with AG compared to AA. AADAC rs1803155 was not associated with des-RPT CL. UGT1A1 rs887829 was associated with both RPT and des-RPT CL in all participants (p=6.3E-19 and p=3.7E-26), the RPT/MFX arm (p=4.5E-16 and p=6.2E-14), and the RPT arm (p=6.8E-6 and p=1.5E-14, respectively). Despite genome-wide significant associations of the UGT1A1 poor metabolizer T allele with more CL of both RPT and des-RPT CL, UGT1A1 only impacted des-RPT CL in PK modeling. Conclusions: In participants receiving 1200 mg RPT daily, the AADAC rs1803155 G allele was associated with increased RPT CL but not des-RPT at genome-wide significance, especially with concomitant MFX, and improved prediction of RPT CL in PK modeling. This helps to explain interindividual variability of RPT PK. Host genetics should be considered when evaluating the efficacy and safety of RPT-containing regimens.

efficient and scalable approach for bolstering the detection of both diseases in high-prevalence settings, but the potential effectiveness is unproven. Methods: A prospective, cross-sectional pilot study was conducted to evaluate a systematic HIV and TB case finding strategy among individuals at SDVs in two high HIV/TB burden communities in Lusaka, Zambia. Persons were eligible if they were age ≥18 years, an SDV patron or employee, not currently receiving TB treatment, willing to get tested for TB, and were without signs of intoxication. All participants underwent rapid HIV testing if they had a negative or unknown status and were evaluated for TB regardless of symptoms using sputum Xpert Ultra and culture. The diagnostic yield and associated number needed to test (NNT) were determined for new HIV and TB diagnoses. Results: Of 582 screened, 448 met eligibility criteria, and 443 had complete data and were included (median age 37 [IQR, 30-44], 71.8% male, 88.3% patrons, 96.8% had AUD (median AUDIT-C 8 [IQR, 8-12]). Overall, 95.9% (n=425) had been previously tested for HIV - 31.8% (n=135) reported being a person living with HIV (PWH), of which 94.1% (n=127) were currently receiving ART. Of 308 participants with an unknown or previously negative HIV status, 10 (3.2%) tested newly positive for HIV (NNT=31); thus, the overall HIV prevalence was 32.7% (n=145). 39.1% (n=173) of participants had previously been tested for TB, 16.3% (n=72) had a prior history of TB disease, and 4.7% (n=21) had newly microbiologically confirmed pulmonary TB (NNT=21). There was a trend toward a higher yield of new HIV diagnoses among patrons compared to employees (3.7% vs. 0%;p=0.29), while there was a higher yield of new TB diagnoses among employees compared to patrons (11.5% vs. 3.8%;p=0.026). Overall, 99.3% (n=443) were willing to participate in a similar program in the future if periodically offered by the Ministry of Health. Conclusions: A novel, integrated case finding strategy at social drinking venues shows substantial promise for increasing HIV and TB detection by delivering services directly to where people with alcohol use disorder gather. Larger studies are needed to confirm its effectiveness and implementability. Effectiveness of Portable Digital X-Ray Machine in Tuberculosis Case-Finding in Nigeria Ademola Adelekan, Aderonke Agbaje, Olugbenga Daniel, Babatunde Pedro, Patrick Dakum Institute of Human Virology Nigeria, Abuja, Nigeria Background: The high tuberculosis (TB) burden in Nigeria, particularly in hard-to-reach and underserved areas, has called for innovative approaches to enhance case-finding. The portable digital X-ray (PDX) machines offer an opportunity to improve TB detection in regions with limited resources and access to more complex diagnostic tools. This paper presents the effectiveness of PDX machines in TB case-finding in Nigeria under the USAID-funded TB-LON 3 project. Methods: This PDX intervention was carried out in purposively selected two (Oyo and Osun) States, Nigeria, from January 2022 to March 2024. The AI enhanced Fujifilm’s Xair and Delft Light Backpack PDX machines were deployed to screen the population of people in communities, schools, correctional centres and orphanages. Presumptive were evaluated using bacteriological laboratory tests and clinical radiology reviews. Data on screening coverage, presumptive TB identification, confirmed diagnoses and treatment initiation were collected and analysed. Results: Overall, 98,863 people were screened within the implementing period, and 52.57% of those screened were from Osun state. Oyo State, however, had a higher presumptive identification (53.07%) and TB diagnoses (53.17%) rate. The PDX machine identified 13.79% (13,630) of those screened as TB presumptive, and almost all (99.4%) were evaluated with other TB diagnostic methods. TB was diagnosed in 14.91% (2,020) of those evaluated, and 94.11% of them were started on treatment. Although more females (57.51%) were screened, the males had a higher proportion (54.11%) of TB diagnosed. Almost all clients screened were relatively distributed among those aged 5 to 65+ years; nonetheless, presumptive identification and case-finding were highest among those aged 65+. Conclusions: Implementing PDX machines significantly improved TB case identification and diagnoses in Osun and Oyo States. The machines effectively identified presumptive TB cases and enhanced TB diagnostic yield. Although AI-enhanced PDX machines have not shown effectiveness in this location as a diagnostic tool, the findings support that it should be adopted as a screening tool on a large scale, especially in resource-limited settings.

Poster Abstracts

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959

High Diagnostic Yield of a Novel HIV-TB Case Finding Strategy at Social Drinking Venues in Zambia Andrew Kerkhoff 1 , David Singini 2 , Solomon Chifwamba 2 , Lawrence Kushukila 2 , Benson Njobvu 2 , Minyoi Maimbolwa 2 , Mary Kagujje 2 , Monde Muyoyeta 2 1 University of California San Francisco, San Francisco, CA, USA, 2 Center for Infectious Disease Research in Zambia, Lusaka, Zambia Background: The high prevalence of alcohol use disorder (AUD) in sub Saharan Africa is strongly associated with HIV acquisition and a greater risk of tuberculosis (TB) disease. An integrated HIV and TB case finding strategy targeting persons with AUD at social drinking venues (SDVs) could be an

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