CROI 2025 Abstract eBook

Abstract eBook

Oral Abstracts

Results: We enrolled 305 (80%) of 383 patients diagnosed with pre-XDR or XDR TB. Median age was 36 years (IQR 30-44), 137 (45%) were female, and 216 (73%) were HIV-positive. TB isolates were sequenced for 253 (83%) participants; 141 (56%) were genotypically linked. Only 13 (9%) genomically clustered participants were linked by close contact. An additional 81 (57%) were linked through casual contact, and 47 (33%) had no identifiable epi link. Casual contact links were found through same named outpatient clinics (n=56, 40%), proximate home or community locations (≤500 meters) (n=39, 28%), or a same named community location (n=10, 7.0%). Inclusion of casual contact in network analysis increased the median degree from 1 (IQR 0-2) to 10 (IQR 5-19) and reduced median shortest path length to 3 (IQR 2-3) among clustered participants. Conclusions: Although a majority of participants were genomically clustered, close contact explained only 9% of links. Casual contact in community locations, including clinics and proximate locations, explained an additional 57% of potential transmission. Future efforts to curb TB transmission will require a greater understanding of unrecognized infectiousness and social mixing in community settings. DOLPHIN-Moms: Pharmacokinetics of Dolutegravir and HIV Viral Suppression With 1HP or 3HP in Pregnancy Jyoti Mathad 1 , Sylvia LaCourse 2 , Belen P. Solans 3 , Jayajothi Moodley 4 , Vaneshree Govender 4 , Tumelo Moloantoa 5 , Marije Van Schalkwyk 6 , Ethel Weld 7 , Letha Varughese 7 , Kelly E. Dooley 8 , Amita Gupta 7 , Radojka M. Savic 3 , Gavin Churchyard 4 , Richard E. Chaisson 7 , for the DOLPHIN-Moms Study 1 Weill Cornell Medicine, New York, NY, USA, 2 University of Washington, Seattle, WA, USA, 3 University of California San Francisco, San Francisco, CA, USA, 4 The Aurum Institute, Johannesburg, South Africa, 5 Perinatal HIV Research Unit, Soweto, South Africa, 6 Stellenbosch University, Cape Town, South Africa, 7 The Johns Hopkins University School of Medicine, Baltimore, MD, USA, 8 Vanderbilt University Medical Center, Nashville, TN, USA Background: The World Health Organization endorses 3 months of weekly isoniazid and rifapentine (3HP) as TB preventive therapy (TPT) in people with HIV (PWH) on once-daily dolutegravir (DTG)-based antiretroviral treatment (ART). Optimal dosing of DTG to maintain HIV viral suppression in pregnancy while taking 3HP or 1 month of daily isoniazid and rifapentine (1HP) has not been studied. Methods : DOLPHIN-Moms (NCT95122026) is an open-label phase II trial in South Africa investigating the safety and pharmacokinetics of DTG in pregnant PWH initiated on 1HP or 3HP. Pregnant PWH at 20-34 weeks’ gestation with HIV viral suppression on DTG-based ART were randomized 1:1 to receive 1HP or 3HP. All initiated twice-daily DTG prior to starting 1HP or 3HP on day 1. Twenty-five participants in each arm had sparse DTG PK sampling on days 1 (pre-HP) and 17 (11h and 12h post DTG dose). DTG dosing was considered acceptable if 5th percentile DTG troughs were >158 ng/mL. HIV viral load was measured at screening, delivery, and TPT completion (1HP: week 4, 3HP: week 12). We estimated population PK of DTG using non-linear mixed effects modeling and performed Monte Carlo simulations of daily DTG dosing with 1HP and 3HP. Results: Among 50 pregnant PWH, at entry, the median age was 33 years (IQR 31–37), gestational age 26.8 weeks (IQR 23–30), and CD4 696 cells/mm 3 (IQR 459–864). All had HIV viral suppression. On day 1, there were no significant differences in median DTG troughs between 1HP and 3HP (2730 vs 2890 ng/ mL, p=0.91). On day 17, median (5th-95th percentile) troughs were 871 ng/mL (391–1754) in the 1HP arm and 1890 ng/mL (843–4764) with 3HP (p<0.01). At day 17, one participant per arm had DTG troughs <64ng/mL (Fig 1A): both had documented nonadherence and received counseling; one had detectable viral load at delivery (6697 copies/mL) and viral suppression at 12 weeks postpartum (3HP arm); the other remained virally suppressed throughout. Excluding these two participants, simulations of once-daily DTG predicted median (5th–95th percentile) DTG troughs of 88ng/mL (28–212) with 1HP and 436ng/mL (209–781) with 3HP. Conclusions: In pregnant PWH, 1HP and 3HP administered with twice-daily DTG yields therapeutic DTG troughs and viral suppression among participants with adherence. Simulations predict once-daily dosing will achieve target DTG concentrations with 3HP but not 1HP. The next phase of the trial (confirming PK and virologic outcomes of once-daily DTG with 3HP in pregnant PWH) is ongoing.

the standard arm (difference 4.1%; 95%CI -2.2% - 10.4%; p=0.204). None of the early deaths were attributed to drug-induced liver injury. Clinical hepatitis events within 14 days occurred in 15 participants in the intensified arm and 21 in the standard arm. Conclusions: Intensified TB treatment was associated with higher 2-week mortality, which has not been observed in prior trials of higher dose rifamycins and fluoroquinolones in TB. Reasons for higher 2-week mortality are currently unclear. Interaction with prednisone will be explored when that randomization is unblinded. Strategies involving higher dose rifamycins and fluoroquinolones should be used with caution in critically ill inpatients with HIV and disseminated TB.

Oral Abstracts

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Casual Contact in Community Settings Explains Majority of TB Transmission in South Africa Neel R. Gandhi 1 , Hikari Yoshii 1 , Kogieleum Naidoo 2 , Keeren Lutchminarain 3 , Linrui Tang 4 , Melanie Chitwood 5 , Shaheed V. Omar 6 , Fay Willis 1 , Angie Campbell 1 , Theodore Cohen 5 , Barun Mathema 4 , James C. M. Brust 7 , Sarita Shah 8 , for the CONTEXT Study Team 1 Emory University, Atlanta, GA, USA, 2 Centre for the AIDS Programme of Research in South Africa, Durban, South Africa, 3 University of KwaZulu-Natal, Durban, South Africa, 4 Columbia University, New York, NY, USA, 5 Yale University, New Haven, CT, USA, 6 National Institute for Communicable Diseases, Johannesburg, South Africa, 7 Albert Einstein College of Medicine, Bronx, NY, USA, 8 Rollins School of Public Health, Atlanta, GA, USA Background: Transmission is the primary driver of drug-resistant (DR) TB epidemics; however, where and between whom spread occurs is poorly understood. Although TB is transmitted through shared air between individuals, numerous studies have demonstrated that <30% of genomically clustered individuals were household or other close contacts. We evaluated the role of casual contact in DR-TB transmission in the Durban metropolitan area in South Africa. Methods: We conducted a prospective study of all XDR and pre-XDR TB patients diagnosed in 2019-2022. Participants were interviewed about homes, hospitals, clinics, and community locations visited regularly, in the 2 years before TB diagnosis. GPS coordinates were collected at all locations. TB isolates underwent whole genome sequencing; a SNP difference of ≤12 was considered genomically clustered. Person-to-person links and overlapping hospital admissions were defined as close contact. Casual contact was based on clinics or community locations named in common or proximate to each other (≤500 meters). Genomic, social network, and spatial analyses were performed to determine the proportion of transmission due to close versus casual contact.

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CROI 2025