Creative Commons Attribution LicenseKarat, Aaron S.Tlali, MphoFielding, Katherine L.Charalambous, SalomeChihota, Violet N.Churchyard, Gavin J.Hanifa, YasmeenJohnson, SuzanneMcCarthy, KerriganMartinson, Neil A.Omar, TanvierKahn, KathleenChandramohan, DanielGrant, Alison D.Isaakidis, Petros2020-01-172020-01-172017-03-23Karat, A. S., Tlali, M., Fielding, K. L., Charalambous, S., Chihota, V. N., Churchyard, G. J., Hanifa, Y., Johnson, S., McCarthy, K., Martinson, N. A., Omar, T., Kahn, K., Chandramohan, D. & Grant, A. D. (2017) Measuring mortality due to HIV-associated tuberculosis among adults in South Africa: Comparing verbal autopsy, minimally-invasive autopsy, and research data. PLOS One, 12(3).1932-6203https://eresearch.qmu.ac.uk/handle/20.500.12289/10432https://doi.org/10.1371/journal.pone.0174097Aaron S. Karat - ORCID 0000-0001-9643-664X https://orcid.org/0000-0001-9643-664XBackground The World Health Organization (WHO) aims to reduce tuberculosis (TB) deaths by 95% by 2035; tracking progress requires accurate measurement of TB mortality. International Classification of Diseases (ICD) codes do not differentiate between HIV-associated TB and HIV more generally. Verbal autopsy (VA) is used to estimate cause of death (CoD) patterns but has mostly been validated against a suboptimal gold standard for HIV and TB. This study, conducted among HIV-positive adults, aimed to estimate the accuracy of VA in ascertaining TB and HIV CoD when compared to a reference standard derived from a variety of clinical sources including, in some, minimally-invasive autopsy (MIA).Methods and findings Decedents were enrolled into a trial of empirical TB treatment or a cohort exploring diagnostic algorithms for TB in South Africa. The WHO 2012 instrument was used; VA CoD were assigned using physician-certified VA (PCVA), InterVA-4, and SmartVA-Analyze. Reference CoD were assigned using MIA, research, and health facility data, as available. 259 VAs were completed: 147 (57%) decedents were female; median age was 39 (interquartile range [IQR] 33±47) years and CD4 count 51 (IQR 22±102) cells/μL. Compared to reference CoD that included MIA (n = 34), VA underestimated mortality due to HIV/AIDS (94% reference, 74% PCVA, 47% InterVA-4, and 41% SmartVA-Analyze; chance-corrected concordance [CCC] 0.71, 0.42, and 0.31, respectively) and HIV-associated TB (41% reference, 32% PCVA; CCC 0.23). For individual decedents, all VA methods agreed poorly with reference CoD that did not include MIA (n = 259; overall CCC 0.14, 0.06, and 0.15 for PCVA, InterVA-4, and SmartVA-Analyze); agreement was better at population level (cause-specific mortality fraction accuracy 0.78, 0.61, and 0.57, for the three methods, respectively).Conclusions Current VA methods underestimate mortality due to HIV-associated TB. ICD and VA methods need modifications that allow for more specific evaluation of HIV-related deaths and direct estimation of mortality due to HIV-associated TB.en© 2017 Karat et al.http://creativecommons.org/licenses/by/4.0/Article