CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

Effect of Smoking on Longitudinal Interferon- ϒ Release Assay Results Among Tuberculosis Contacts Maria B Arriaga , Gustavo Amorim Vanderbilt University, Nashville, TN, USA Background: Diagnosis of M. tuberculosis (Mtb) infection in close tuberculosis (TB) contacts is critical for TB control. Interferon-gamma release assays (IGRAs) diagnose Mtb infection, but the test is limited by assay variability, including the conversion (negative to positive) and reversion (positive to negative) of IGRA responses that may not always reflect changes in Mtb infection status. Several studies have revealed that smoking is a risk factor for Mtb infection and TB disease but its effect on longitudinal IGRA results remains unknown. Methods: We conducted a multi-site prospective study in RePORT-Brazil between 2015-2019 among close contacts of adults with culture-confirmed pulmonary TB. IGRA testing was performed at baseline, month 6 and month 24-30 after enrollment. IGRA results were categorized as IGRA-positive (maintained from baseline to last visit), IGRA-conversion (from negative to positive at any time), IGRA-reversion (from positive to negative at any time), and IGRA-negative (maintained from baseline to last visit). Associations between IGRA results and smoking status at baseline (current/former vs never) in contacts were evaluated using propensity score-adjusted logistic regression models to avoid overfitting. More specifically, we first estimated the propensity of smoking using Lasso. Next, this estimated propensity score was used as a covariate in the main outcome model, which regressed the outcome (IGRA positive, IGRA-conversion, IGRA-reversion) on smoking status. Results: There were 430 close contacts of 139 TB cases. Of the contacts, 89 (21%) were IGRA-positive, 30 (7%) were converters, and 30 (7%) were reverters; 22 (5.1%) had an indeterminate result. The frequency of smoking among contacts was 26 (29.2%), 7 (23.3%) and 3 (10%) in IGRA-positive, IGRA conversion and IGRA-reversion groups, correspondingly. Smoking in contacts was associated with lower odds for IGRA-reversion (adjusted odds ratio=0.09; 95% confidence interval=[0.01;0.73]). We did not detect associations between smoking and IGRA-positive or IGRA-conversion at the 5% level. Conclusion: Contacts who reported smoking (past/former) had lower odds of reverting from an IGRA-positive to an IGRA-negative result. Our findings highlight the importance of smoking on longitudinal IGRA results. This has implications for clinical care and clinical trials in which IGRA status is monitored or used as an outcome, such as TB vaccine trials.

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Cryptococcal Meningitis as an Indicator for Monitoring HIV Treatment Program Success in Botswana James Milburn 1 , Ookeditse Ntwayagae 2 , Rachita Suresh 3 , Kebatshabile Ngoni 3 , Tony Chebani 4 , Tshepo B. Leeme 3 , David S. Lawrence 1 , Daniel Grint 1 , Mark W. Tenforde 5 , Ava Avalos 3 , Dinah Ramaabya 4 , Justus Ogando 6 , Margaret Mokomane 7 , Madisa Mine 8 , Joseph N. Jarvis 1 1 London School of Hygiene & Tropical Medicine, London, United Kingdom, 2 Botswana–University of Maryland School of Medicine Health Initiative, Gaborone, Botswana, 3 Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana, 4 Botswana Ministry of Health, Gaborone, Botswana, 5 Botswana–UPenn Partnership, Gaborone, Botswana, 6 Clinton Health Access Initiative, Nairobi, Kenya, 7 University of Botswana, Gaborone, Botswana, 8 National Health Laboratory, Gaborone, Botswana Background: Cryptococcal meningitis (CM) remains a frequent opportunistic infection among individuals living with advanced HIV disease (AHD) in much of Africa. Despite widespread expansion of ART programmes, modelled estimates indicate that the incidence of CM has not substantially decreased between 2014 and 2020, suggesting that the prevalence of AHD remains high in the region. CM incidence could provide a useful indicator for monitoring AHD rates and HIV program success, especially in the context of declining access to CD4 testing; most patients present to healthcare facilities with a well-defined clinical syndrome, and diagnosis can be made using low-cost and highly accurate rapid diagnostic tests. Very few countries collect reliable statistics on CM incidence, and the impact of WHO universal HIV treatment guidelines on the incidence of AHD is not known. Methods: We analyzed 8 years of national meningitis surveillance data (2015-2022) captured from electronic health records in Botswana. All laboratory records from cerebrospinal fluid samples analysed within government healthcare facilities in Botswana were extracted from a central online repository. Adjustments for missing data were made based on triangulation for underestimates using comprehensive prospective datasets. CM case frequency was enumerated using a case definition and incidence was calculated using national census data. Results: A total of 1,744 episodes of CM were identified. The estimated national incidence of CM in Botswana approximately halved between 2015 and 2022, from 15.0 cases/100,000 person years (PYO) (95% CI 13.5-16.7 cases/100,00) to 7.43 cases/100,000 PYO (95% CI 6.4-8.6 cases/100,000). Among all people living with HIV, the incidence of CM decreased from 92.0 cases/100,000 PYO (95% CI 82.2-102.6 cases/100,000 PYO) to 49.1 cases/100,000 PYO (95% CI 42.2-57.0 cases/100,000 PYO) between 2015 and 2022. There was no clear increase in the rate of decline following the introduction of universal treatment in 2016. The highest incidence was observed in men and individuals aged 40-44. The proportion of cases diagnosed through rapid cryptococcal antigen (CrAg) testing increased during the study period from 35.5% to 86.3%. Conclusion: CM incidence has decreased with expanded ART treatment but persists at a relatively high rate despite excellent reported ART coverage. Most cases are now diagnosed through the rapid CrAg lateral flow assay highlighting the potential of using CM as key indicator for programme success in the Treat All era.

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Poster Abstracts

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Viral Suppression Among Adults Receiving Dolutegravir-Based ART and 3-Months Isoniazid-Rifapentine Lelia H Chaisson 1 , Shafic Makumbi 2 , David Dowdy 3 , Carina Marquez 4 , Derek T. Armstrong 5 , Bishop Opira 2 , Patrick P. Phillips 4 , Fred C. Semitala 6 , Christina Yoon 4 1 University of Illinois at Chicago, Chicago, IL, USA, 2 Infectious Diseases Research Collaboration, Kampala, Uganda, 3 The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, 4 University of California San Francisco, San Francisco, CA, USA, 5 The Johns Hopkins University School of Medicine, Baltimore, MD, USA, 6 Makerere University College of Health Sciences, Kampala, Uganda Background: Prior studies have reported conflicting results regarding the safety and/or effectiveness of rifapentine-based tuberculosis (TB) preventive therapy with dolutegravir (DTG)-based ART. In an interim analysis, we previously found that co-administration of 3HP (3 months weekly isoniazid+rifapentine) with TDF/3TC/DTG (TLD) was safe for adults initiating routine ART, but that those who received 3HP+TLD were less likely to achieve 6-month viral suppression compared to those who received TLD alone. Here, we present an updated analysis of 1) safety of 3HP+TLD and 2) viral suppression among those initiating 3HP+TLD vs TLD alone. Methods: In an ongoing phase 3 randomized trial comparing two TB screening strategies among adults with HIV initiating routine ART in Uganda (NCT04557176), participants who screened negative for TB were assessed for

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