Antiretroviral therapy for tuberculosis control in nine African countries

Abstract

HIV has increased the incidence of tuberculosis (TB) by up to sevenfold in African countries, but antiretroviral therapy (ART) reduces the incidence of AIDS-related TB. We use a mathematical model to investigate the short-term and long-term impacts of ART on the incidence of TB, assuming that people are tested for HIV once a year, on average, and start ART at a fixed time after HIV seroconversion or at a fixed CD4(+) cell count. We fit the model to trend data on HIV prevalence and TB incidence in nine countries in sub-Saharan Africa. If HIV-positive people start ART within 5 y of seroconversion, the incidence of AIDS-related TB in 2015 will be reduced by 48% (range: 37-55%). Long-term reductions depend sensitively on the delay to starting ART. If treatment is started 5, 2, or 1 y after HIV seroconversion, or as soon as people test positive, the incidence in 2050 will be reduced by 66% (range: 57-80%), 95% (range: 93-96%), 97.7% (range: 96.9-98.2%) and 98.4% (range: 97.8-98.9%), respectively. In the countries considered here, early ART could avert 0.71 ± 0.36 [95% confidence interval (CI)] million of 3.4 million cases of TB between 2010 and 2015 and 5.8 ± 2.9 (95% CI) million of 15 million cases between 2015 and 2050. As more countries provide ART at higher CD4(+) cell counts, the impact on TB should be investigated to test the predictions of this model.

Fig. 1.

(Left) HIV prevalence (red line), annual incidence (blue), annual mortality (black), and prevalence in adults aged 15–49 y (red dots) (6). (Center) TB notification rates per 100,000 population per year (red dots) (1), fitted estimate (red line), and notifications in HIV-negative people (blue line). (Right) , TB incidence rate ratio in HIV-positive compared with HIV-negative people. Note the different vertical scales.

Fig. 2.

, the TB incidence rate ratio for HIV-positive people on ART compared with those not on ART in 2015 (A) and 2050 (B) plotted against , the TB incidence rate ratio for HIV-positive adults compared with HIV-negative people. People start ART if they have been infected for more than 5 y (black), 2 y (red), 1 y (blue), or immediately (green). The dots indicate countries (left to right): Botswana, Lesotho, South Africa, Swaziland, Malawi, Ghana, Zambia, Gabon, and Tanzania. The lines are exponential trend lines fitted to the data. Error bars show the systematic uncertainty in the overall estimates.

Fig. 3.

Impact of ART on the TB notification rate per 100,000 population per year. In all cases, we assume that people are tested once a year, on average. The columns (left to right) show the impact of starting ART when the CD4⁺ cell count is 200, 350, or 500 cells/μL or starting immediately irrespective of CD4 cell count. The rows (top to bottom) show the model estimates for Botswana, Ghana, and South Africa. Dark blue lines indicate HIV-negative people, pink lines indicate HIV-positive people not on ART, light blue lines indicate HIV-positive people on ART, red lines indicate total, and red dots indicate data (6).