Abstract
BackgroundAlthough 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.Methodology/Principal FindingsProspectively 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).Conclusions/SignificanceTB 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.
Highlights
As the 2015 end-point for the Millennium Development Goals approaches, HIV-associated tuberculosis (TB) remains a substantial challenge to global health, accounting for 13% (1.1 million) of new TB cases and approximately 25% of global deaths from HIV/AIDS [1]
The large size of this cohort, prolonged follow-up, high rates of microbiological diagnosis and frequent CD4 count and viral load measurements allowed us to calculate with greater precision than existing studies how long-term TB incidence rates vary according to duration of antiretroviral therapy (ART) and degree of CD4 cell count recovery
Beyond the first year of ART, TB incidence rates remained fairly constant, ranging between 6.71 and 4.92 cases/ 100PYs, and TB risk was not associated with increasing duration of ART in multivariate analysis
Summary
As the 2015 end-point for the Millennium Development Goals approaches, HIV-associated tuberculosis (TB) remains a substantial challenge to global health, accounting for 13% (1.1 million) of new TB cases and approximately 25% of global deaths from HIV/AIDS [1]. 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
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