Tuberculosis Incidence Rates during 8 Years of Follow-Up of an Antiretroviral Treatment Cohort in South Africa: Comparison with Rates in the Community

Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.
PLoS ONE (Impact Factor: 3.23). 03/2012; 7(3):e34156. DOI: 10.1371/journal.pone.0034156
Source: PubMed


Although antiretroviral therapy (ART) is known to be associated with time-dependent reductions in tuberculosis (TB) incidence, the long-term impact of ART on incidence remains imprecisely defined due to limited duration of follow-up and incomplete CD4 cell count recovery in existing studies. We determined TB incidence in a South African ART cohort with up to 8 years of follow-up and stratified rates according to CD4 cell count recovery. We compared these rates with those of HIV-uninfected individuals living in the same community.
Prospectively collected clinical data on patients receiving ART in a community-based cohort in Cape Town were analysed. 1544 patients with a median follow-up of 5.0 years (IQR 2.4-5.8) were included in the analysis. 484 episodes of incident TB (73.6% culture-confirmed) were diagnosed in 424 patients during 6506 person-years (PYs) of follow-up. The TB incidence rate during the first year of ART was 12.4 (95% CI 10.8-14.4) cases/100PYs and decreased to 4.92 (95% CI 3.64-8.62) cases/100PYs between 5 and 8 years of ART. During person-time accrued within CD4 cell strata 0-100, 101-200, 201-300, 301-400, 401-500, 501-700 and ≥700 cells/µL, TB incidence rates (95% CI) were 25.5 (21.6-30.3), 11.2 (9.4-13.5), 7.9 (6.4-9.7), 5.0 (3.9-6.6), 5.1 (3.8-6.8), 4.1 (3.1-5.4) and 2.7 (1.7-4.5) cases/100PYs, respectively. Overall, 75% (95% CI 70.9-78.8) of TB episodes were recurrent cases. Updated CD4 cell count and viral load measurements were independently associated with long-term TB risk. TB rates during person-time accrued in the highest CD4 cell count stratum (>700 cells/µL) were 4.4-fold higher that the rate in HIV uninfected individuals living in the same community (2.7 versus 0.62 cases/100PYs; 95%CI 0.58-0.65).
TB rates during long-term ART remained substantially greater than rates in the local HIV uninfected populations regardless of duration of ART or attainment of CD4 cell counts exceeding 700 cells/µL.

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    • "While continued scale-up of antiretroviral therapy programs is important, multiple studies have suggested that tuberculosis incidence among persons on antiretroviral therapy and with high CD4 counts still exceeds incidence in the HIV-negative population [23]–[25]. Therefore, additional interventions will be necessary if the disparity in tuberculosis incidence between persons with and without HIV is to be addressed. These include identification of all persons living with HIV, early initiation of antiretroviral therapy, routine symptom-based screening for tuberculosis disease, and provision of tuberculosis preventive therapy to prevent development of tuberculosis disease. "
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    • "Previous studies attributed the great reduction of TB incidence, in the short term, to cART initiation [21-23]. In our study, we demonstrate a significant decrease in TB incidence density rate also among patients who never started cART during the second year. "
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    • "Despite these promising short-term observations, the long-term impact of ART scale-up on TB incidence rates at the population level remains unknown and will depend on a number of factors. TB rates after 8 years of follow-up in a South African ART cohort remained several-fold higher than those in non-HIV-infected people in the same community, even among those with the greatest CD4 cell count recovery [10]. Longer-term responses to ART are unknown but as ART services have expanded over time, reports from the region describe increasing rates of programme loss to follow-up and virological failure [11], [12]. "
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