Quantifying missed opportunities for tuberculosis among people with HIV in the US President's Emergency Plan for AIDS Relief

The US President's Emergency Plan for AIDS Relief (PEPFAR) is the largest HIV program globally, serving roughly 58% of the estimated 28.7 million people with HIV (PWH) on antiretroviral therapy (ART) in 2021 [1,2]. Tuberculosis (TB) remains the leading cause of death among PWH; an estimated 46% of TB cases are undiagnosed at the time of death, emphasizing the challenge of TB detection among this population [3]. The WHO four-symptom screen at every clinical encounter is the primary TB case finding strategy implemented in PEPFAR. Recent program data show 87% of PWH were screened for TB symptoms and, among those, only 2.7% screened positive and were referred for further TB evaluation [2]. Although the expected rate of TB symptom positivity among PWH is debated, PEPFAR's yield is not yet optimal compared with reports from the literature ranging from 30% to 67% [4]. Poor case detection leads to PWH with undiagnosed, untreated, and unreported TB, which contributes to subsequent TB-attributable mortality among PWH. The extent of gaps in case detection and mortality have been difficult to quantify. We estimated the number of missed TB/HIV diagnoses and TB-attributable deaths in the populations PEPFAR serves using data from PEPFAR, WHO, and the Joint United Nations Programme on HIV/AIDS (UNAIDS) [1,5]. Data was analyzed for 2018–2021, reflecting data from before the COVID-19 pandemic through the most recently available year. WHO and UNAIDS reporting periods were aligned with PEPFAR data wherever possible. Country-level data was analyzed by year for the 32 countries where PEPFAR operated and reported TB data. All datasets were downloaded in April 2023 and analyzed in Tableau, version 2022.1. As PEPFAR support in countries is not always nationwide, we divided the number of PWH who received ART through PEPFAR by the national number reported to UNAIDS for each country to calculate annualized program coverage; coverage was capped at 100%. We applied this proportion to the estimated TB/HIV incidence from WHO to approximate the number of PWH with TB in PEPFAR-supported populations (irrespective of ART status). We then subtracted the number of PWH with TB that PEPFAR reported to approximate missed TB diagnoses. We used WHO data to estimate TB-attributable mortality among PWH and applied this to the estimated number of PWH with TB in PEPFAR-supported populations, calculated above. In 2021, we estimated that 386 862 PWH had TB in PEPFAR-supported countries. In the same year, PEPFAR reported 144 146 PWH with TB were detected and initiated on TB treatment; thus, we estimated 242 716 (63%) TB diagnoses were missed. We estimate that 106 967 PWH suffered TB-attributable mortality in 2021. Although PEPFAR has an indicator on mortality, reporting is not mandatory and, therefore, data are considered incomplete. For example, PEPFAR's most recent data reported only 1645 TB-attributable deaths among nearly 18 million PWH program beneficiaries. Our estimates suggest that while the number of missed TB diagnoses among PWH has decreased since last year, there has been an overall increase since 2018 (Fig. 1). Mortality estimates have been steadily decreasing since 2018.Fig. 1: Trends in missed tuberculosis diagnoses and tuberculosis-attributable mortality among persons with HIV, the United States President's Emergency Plan for AIDS Relief, 2018–2021.These approaches are limited by the quality of data reported to PEPFAR and UNAIDS and the accuracy of WHO estimates. TB diagnosis and treatment information for PWH who received ART in PEPFAR may not have been entered into PEPFAR-reporting systems, resulting in an underrepresentation of TB diagnoses. Additionally, national TB/HIV incidence and mortality estimates are not available by ART status. ART is known to have a strong preventive effect on TB incidence. Meta-analyses estimated a 67% risk reduction for TB among PWH who received ART compared with those who did not receive ART [6,7]. Our missed TB diagnoses and mortality estimates therefore may be more accurate for countries where ART coverage was high, leading to more uniform incidence and mortality rates among PWH. Among the PEPFAR-supported countries included in this analysis, the median national ART coverage was 80% (range: 20–60%) as estimated by UNAIDS [1]. Despite these limitations, our analyses provide more refined reference points when discussing missed TB diagnoses and TB/HIV mortality in PEPFAR programming that have been lacking to date. Renewed urgency and implementation of the latest recommended screening and diagnostic strategies will be critically important in our global efforts to further reduce the TB burden among PWH [8,9]. This analysis also highlights the challenges in developing estimates and quantifying gaps related to HIV-associated TB, particularly at subnational levels. Further progress is possible with improved coordination between national data systems for TB and HIV and the standardization of data collection and collation into global data systems in PEPFAR, WHO, and UNAIDS. Acknowledgements The findings and conclusions in this article are those of the authors and do not necessarily represent the official position of the author's agencies, namely USAID, CDC, WHO, and the Stop TB Partnership. Funding: Data collection and analysis has been supported by the President's Emergency Plan for AIDS Relief (PEPFAR) through the US Agency for International Development (USAID) and Centers for Disease Control and Prevention (CDC). Conflicts of interest There are no conflicts of interest.