Incidence of self-reported tuberculosis treatment with community-wide universal testing and treatment for HIV and tuberculosis screening in Zambia and South Africa: A planned analysis of the HPTN 071 (PopART) cluster-randomised trial

Background HIV is a potent risk factor for tuberculosis (TB). Therefore, community-wide universal testing and treatment for HIV (UTT) could contribute to TB control, but evidence for this is limited. Community-wide TB screening can decrease population-level TB prevalence. Combining UTT with TB screening could therefore significantly impact TB control in sub-Saharan Africa, but to our knowledge there is no evidence for this combined approach. Methods and findings HPTN 071 (PopART) was a community-randomised trial conducted between November 2013 to July 2018; 21 Zambian and South African communities (with a total population of approximately 1 million individuals) were randomised to arms A (community-wide UTT and TB screening), B (community-wide universal HIV testing with treatment following national guidelines and TB screening), or C (standard-of-care). In a cohort of randomly selected adults (18 to 44 years) enrolled between 2013 and 2015 from all 21 communities (total size 38,474; 27,139 [71%] female; 8,004 [21%] HIV positive) and followed-up annually for 36 months to measure the population-level impact of the interventions, data on self-reported TB treatment in the previous 12 months (self-reported TB) were collected by trained research assistants and recorded using a structured questionnaire at each study visit. In this prespecified analysis of the trial, self-reported TB incidence rates were measured by calendar year between 2014 and 2017/2018. A p-value <= 0.05 on hypothesis testing was defined as reaching statistical significance. Between January 2014 and July 2018, 38,287 individuals were followed-up: 494 self-reported TB during 104,877 person-years. Overall incidence rates were similar across all arms in 2014 and 2015 (0.33 to 0.46/100 person-years). In 2016 incidence rates were lower in arm A compared to C overall (adjusted rate ratio [aRR] 0.48 [95% confidence interval (95% CI) 0.28 to 0.81; p = 0.01]), with statistical significance reached. In 2017/2018, while incidence rates were lower in arm A compared to C, statistical significance was not reached (aRR 0.58 [95% CI 0.27 to 1.22; p = 0.13]). Among people living with HIV (PLHIV) incidence rates were lower in arm A compared to C in 2016 (RR 0.56 [95% CI 0.29 to 1.08; p = 0.08]) and 2017/2018 (RR 0.50 [95% CI 0.26 to 0.95; p = 0.04]); statistical significance was only reached in 2017/2018. Incidence rates in arms B and C were similar, overall and among PLHIV. Among HIV-negative individuals, there were too few events for cross-arm comparisons. Study limitations include the use of self-report which may have been subject to under-reporting, limited covariate adjustment due to the small number of events, and high losses to follow-up over time. Conclusions In this study, community-wide UTT and TB screening resulted in substantially lower TB incidence among PLHIV at population-level, compared to standard-of-care, with statistical significance reached in the final study year. There was also some evidence this translated to a decrease in self-reported TB incidence overall in the population. Reduction in arm A but not B suggests UTT drove the observed effect. Our data support the role of UTT in TB control, in addition to HIV control, in high TB/HIV burden settings. Lily Telisinghe and co-workers study self-reported tuberculosis incidence among communities in Zambia and South Africa in the PopART trial of universal HIV testing and treatment and tuberculosis screening. Author summary Why was this study done? Tuberculosis (TB) is a leading cause of sickness and death worldwide. In sub-Saharan Africa, TB is mainly driven by the HIV-epidemic. Between 2013 and 2018, the HPTN 071 cluster-randomised trial was conducted in 21 Zambian and South African communities. There were 3 study arms: (1) arm A which received universal testing and treatment for HIV (UTT) and TB screening; (2) arm B which received universal HIV testing (with antiretroviral therapy (ART) according to national guidelines) and TB screening; and (3) arm C the control. As part of the trial, a cohort of 38,474 adults aged 18 to 44 years were enrolled from all communities at the start and followed-up annually over 36 months. What did the researchers do and find? All cohort members were asked if they had been started on TB treatment in the last 12 months (self-reported TB), at each annual visit (maximum of 4 visits). We investigated the effect of the interventions on self-reported TB incidence. We found a decrease in self-reported TB incidence among people living with HIV in arm A compared to arm C. There was also some evidence this translated to a decrease in self-reported TB incidence overall in the population in arm A compared to arm C. Self-reported TB incidence was similar in arms B and C, overall in the population and among people living with HIV. We could not determine the effect of the interventions on self-reported TB incidence among those who were HIV negative, due to the small number of events. What do these findings mean? The decrease in self-reported TB incidence in arm A (which received community-wide UTT and TB screening) but not arm B (which received community-wide HIV testing with ART according to national guidelines and TB screening) suggests the UTT component of the intervention drove the changes observed in arm A. Our data support the role of UTT in TB control in sub-Saharan Africa.