Tuberculosis incidence rates during 8 years of follow-up of an antiretroviral treatment cohort in South Africa: comparison with rates in the community

Ankur Gupta, Robin Wood, Richard Kaplan, Linda-Gail Bekker, Stephen D Lawn, Ankur Gupta, Robin Wood, Richard Kaplan, Linda-Gail Bekker, Stephen D Lawn

Abstract

Background: 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.

Methodology/principal findings: 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).

Conclusions/significance: 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.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Patient enrolment and outcomes during…
Figure 1. Patient enrolment and outcomes during follow-up.
Figure 2. Proportions of person-time accrued in…
Figure 2. Proportions of person-time accrued in updated CD4 cell count strata by duration of antiretroviral therapy (months) for the whole study cohort.
Figure 3. Graph comparing tuberculosis (TB) rates…
Figure 3. Graph comparing tuberculosis (TB) rates and 95% confidence intervals for the study cohort, local population and South Africa national notification rates.
TB rates (cases/100 person-years, [95% CI]) for patients on long-term ART >5 years (4.92, [3.64–8.62]), during person-time accrued with updated CD4 cell counts >700 cells/µL (2.70, [1.73–4.47]), the HIV uninfected population (0.62, [0.58–0.65]) and overall population (1.01, [0.97–1.04) of the local community in 2009, and the South Africa national TB notification rates in 2009 (0.68, [0.678–0.682]).

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Source: PubMed

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