Antiretroviral therapy for control of the HIV-associated tuberculosis epidemic in resource-limited settings

Abstract

Great progress has been made over the past few years in HIV testing in patients who have tuberculosis (TB) and in the scale-up of antiretroviral therapy. More than 3 million people in resource-limited settings were estimated to have started antiretroviral therapy by the end of 2007 and 2 million of these were in sub-Saharan Africa. However, little is known about what impact this massive public health intervention will have on the HIV-associated TB epidemic or how antiretroviral therapy might be used to best effect TB control. This article provides an in-depth review of these issues.

Fig. 1

Estimated TB incidence rates by country for 2006. (Reproduced from World Health Organization. Global Tuberculosis Control. Surveillance, planning, and financing. WHO/HTM/TB/2008.393. Geneva (Switzerland): World Health Organization; 2008; with permission.)

Fig. 2

TB incidence (cases per 100 person-years) among patients who were HIV-infected in Cape Town, South Africa, who were or were not receiving antiretroviral therapy. Patients were stratified according to baseline CD4 cell count and WHO stage of disease. Overall, TB rates were approximately 80% lower among those receiving ART, which was observed across a broad spectrum of baseline immunodeficiency. (Data from Badri M, Wilson D, Wood R. Effect of highly active antiretroviral therapy on incidence of tuberculosis in South Africa: a cohort study. Lancet 2002;359(9323):2059–64).

Fig. 3

TB incidence rates during ART. The graph shows data from studies included in (see Table 2) in which changing TB incidence rates were calculated according to increasing duration of ART. The two lowest curves present data from studies conducted in high-income countries. The remaining four studies are from South Africa (diamonds and inverted triangles¹⁴), a range of resource-limited countries (circles¹⁵), and Uganda (squares¹⁶).

Fig. 4

Decreasing TB incidence rates (cases/100 person-years, white squares) and rising median CD4 cell counts (cells/μL, black diamonds) during the first 3 years of ART. These data are from a community-based ART cohort in a township in Cape Town, South Africa. (Data from Refs.^13,19,56).

Fig. 5

Relationship between updated CD4 cell-count measurements made every 4 months during 4.5 years of ART in a treatment cohort in a township in Cape Town, South Africa. Observed rates are shown as diamonds together with 95% confidence intervals indicated by bars. A logarithmic trend line is overlaid (R² = 0.97). TB incidence rates are seen to fall substantially as CD4 cell counts increase during ART. (Data from Lawn SD, Myer L, Edwards D, et al. Short-term and long-term risk of tuberculosis associated with CD4 cell recovery during antiretroviral therapy in South Africa. AIDS 2009;23(13):1717–25.)