CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

potential to enhance adherence, minimize treatment interruptions, improve completion rates, and extend protection against tuberculosis. Methods: We conducted a cross-sectional in-person survey among patients in two high-burden TB countries to evaluate preferences, and concerns about LA formulations for TPT. The survey compared oral medication to long-acting injections; implants; and microneedle patches. An online survey of healthcare providers (HCP) in low- and middle-income countries (LMIC) assessed attitudes toward and perceived feasibility of implementing LA formulations of TPT. Data are summarized by descriptive statistics. Results: We recruited 409 patients (India, n = 209; South Africa, n = 200) and 94 HCPs from 25 LMIC. Mean age of patient respondents was 40; 35% were male, and 26% reported a history of TPT. Injectable TPT was the most preferred modality, followed by pills, implants, and lastly microneedle patches (Figure 1a). Notably, 304 patients (75%) expressed a strong willingness to try injectable TPT, particularly among those with prior use of injectable medication compared to those without (73% versus 27%; p <0.001). 207 (68%) of patients thought injectable TPT would be the most effective. Among parents and guardians, 75% (132 of 176) of those with children <12 years and 79% (127 of 161) of those with children ≥12 years were willing to have their child receive injectable TPT. For adults, the perceived benefits of injectables compared to pills included ease of administration (79%) and perceived efficacy (75%). However, 45% of patients expressed concern about the potential ineffectiveness and prolonged side effects of injections (40%). 90% (73/81) of providers were willing to prescribe LA TPT if efficacy, safety, and cost are comparable to oral medication. Among providers, 43% (34/79) favoured injectables, while 18% (14/79) favoured implants and 13% (10/79) patches (Figure 1b). Cost emerged as a significant factor influencing providers’ willingness to adopt LA TPT, with 75% willingness if cost is comparable to oral medication compared to 25% if cost were doubled. Conclusions: Injectable TPT was the preferred LA TPT formulation among patients and providers in our survey. At scale, injectable TPT may be highly acceptable and feasible if concerns of cost and safety are addressed.

PBMCs were stained for markers of T cell lineage (CD3, CD4, CD8), activation, and differentiation (PD1, CD45RA, HLA-DR, Ki-67, TIM3, CD38, CD153, CD95). Intracellular cytokine staining for TNF-α, IFN-γ, and IL-2 was performed to assess function. Samples were then analyzed via flow cytometry. Primary analyses investigated changes (Δ) in Mtb -specific T cell phenotype and cytokine responses from pre-TPT to post-TPT. We also explored these changes by TPT treatment arms. Results: Samples in 27 participants from 4 countries were included. Overall, Mtb -specific CD4 and CD8 T cell phenotype, differentiation, and functional attributes were similar pre- and post-TPT. The frequency of WCTBL-specific TNF-α+ CD8 T cells increased post-TPT, compared with pre-TPT (n=27, median Δ +0.17%, p=.006). Compared to pre-TPT, the percentage of activated (CD38 HLA-DR+) WCTBL- and ESAT-6/CFP-10-specific CD8 T cells decreased post-TPT (n=16, Δ -3.8%, p=.044; n=9; Δ -8.1%, p=.039, respectively). The percentage of CD153+ ESAT-6/CFP-10-specific CD8 T cells also decreased post-TPT (n=9, Δ -5.9%, p=.012). Pre- and post-TPT comparisons between INH/RPT and INH treatment arms showed no consistent differences. Conclusions: TPT had little effect on Mtb -specific CD4 and CD8 T cell phenotypic and functional profiles, although modest changes were observed in CD8 T cell activation and TNF-α production post-TPT. Our results suggest that TPT does not substantially modify TB-specific T cell responses in PWH and LTBI, thus supporting a need for novel TB vaccine strategies to boost TB immunity regardless of TPT. Uptake of New Guidelines for Cryptococcal Meningitis in Botswana, Malawi, Uganda, and Zimbabwe Jane Gakuru 1 , Eltas Nyirenda Dziwani 2 , Tshepo Leeme 3 , Constantine Mutata 4 , David B. Meya 1 , Mosepele Mosepele 5 , Henry Mwandumba 2 , Chiratidzo Ndhlovu 4 , Síle Molloy 6 , Thomas S. Harrison 6 , Joseph N. Jarvis 7 , David S. Lawrence 7 1 Infectious Diseases Institute, Kampala, Uganda, 2 Malawi Liverpool Wellcome Trust, Blantyre, Malawi, 3 University of Botswana, 4 University of Zimbabwe, Harare, Zimbabwe, 5 Botswana Harvard AIDS Institute Partnership, Gabarone, Botswana, 6 St George's University of London, London, UK, 7 London School of Hygiene & Tropical Medicine, London, UK Background: WHO guidelines for HIV-associated cryptococcal meningitis were updated in June 2022 recommending single, high-dose liposomal amphotericin with 14 days of flucytosine and fluconazole. The AMBITION team who defined that regimen lead the Single High-dose AmBisome to Reduce Mortality from CM (SHARE-CM) project aiming to maximise the impact of the regimen in routine care. The project engages key stakeholders, trains healthcare workers, increases patient health-related literacy, and undertakes M&E of impact. We report progress after the first 3 years of this 5-year project. Methods: We identified personnel at Ministries of Health and a purposively selected sample of healthcare facilities in Botswana, Malawi, Uganda and Zimbabwe. We administered national level surveys to understand current treatment guidelines, drug registration status, and drug availability. We administered facility level surveys to determine the availability of key commodities and ascertain which treatment regimens are most administered to patients. Surveys were completed online and data described. Results: Four national surveys and 60 facility surveys (Botswana: 13, Malawi: 13, Zimbabwe 14, Uganda: 20) were completed between June 2023 - July 2024. The AMBITION regimen was first-line in each country guideline; timing of guideline dissemination varied. Key antifungals were available in each country, initially via Unitaid/CHAI funding and recently via the Global Fund. CD4 testing was available all or most of the time in 88% (53/60) of facilities; cryptococcal antigen 100% (60/60); lumbar puncture needles 63% (38/60) and manometers 25% (15/60). Liposomal amphotericin was available all or most of the time in 68% (41/60) of facilities; flucytosine 55% (33/60) and fluconazole 82% (49/60). The AMBITION regimen was the most administered regimen overall in 47% (28/60) of facilities with significant intercountry variability ranging from 15% (2/13) in Botswana to 75% in Uganda (15/20). Conclusions: In the two years since WHO guidelines were updated, there has been rapid adoption of the AMBITION regimen in high-incidence settings. Antifungals are available in country but not always at facility level, highlighting the need to improve in-country supply chains. The AMBITION regimen was the most administered overall, with intercountry variability likely explained by different timing of guideline dissemination. Ongoing monitoring and evaluation can support improved uptake of the AMBITION regimen.

Poster Abstracts

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Effect of Tuberculosis Preventive Therapy on Mtb-Specific T-Cell Profile in the A5279/BRIEF TB Trial Pablo C. Alarcon 1 , Xinyu Du 2 , Manuel G. Feria 1 , Ashley McKhann 2 , Michelle A. Kendall 2 , Michael L. Freeman 3 , Susan Swindells 4 , Amita Gupta 5 , Gavin Churchyard 6 , Richard E. Chaisson 5 , Cheryl Day 7 , Moises Huaman 1 1 University of Cincinnati Medical Center, Cincinnati, OH, USA, 2 Harvard TH Chan School of Public Health, Boston, MA, USA, 3 Case Western Reserve University, Cleveland, OH, USA, 4 University of Nebraska Medical Center, Omaha, NE, USA, 5 The Johns Hopkins University School of Medicine, Baltimore, MD, USA, 6 The Aurum Institute, Johannesburg, South Africa, 7 Emory University, Atlanta, GA, USA Background: People with HIV (PWH) have impaired Mycobacterium tuberculosis (Mtb) -specific T cell responses, making induction of effective immunity challenging. Whether TB preventive therapy (TPT) modifies Mtb -specific T cell profile in PWH is unknown. We interrogated Mtb antigen-specific T cell responses in PWH with latent TB infection (LTBI) pre- and post-TPT within the ACTG A5279 clinical trial, a phase III trial of PWH comparing 4 weeks of daily isoniazid/rifapentine (INH/RPT) to 9 months of daily INH. Methods: Cryopreserved PBMCs were obtained pre-TPT (week 0) and post-TPT (week 48) from A5279 participants with LTBI (TST+ or IGRA+) on stable antiretroviral therapy, HIV viral load <200 copies/mL, and CD4 count >100 cells/mm 3 at study entry. PBMCs were thawed and stimulated overnight with CMV pp65 peptide pool, Mtb ESAT-6/CFP-10 peptide pool, and whole cell Mtb lysate (WCTBL). Cells incubated in media alone served as a negative control.

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