The Impact of Anti-Retroviral Therapy on Tuberculosis Detection at the National Level in South Africa

Abstract

Human immunodeficiency virus/tuberculosis (HIV/TB) coinfection is particularly prevalent in South Africa, where TB has been the leading cause of death for more than a decade. The 2004-2008 national rollout of antiretroviral therapy (ART) provides a unique opportunity to examine the population-level impact of ART on the TB epidemic. We performed longitudinal regression analysis to follow the evolution of TB outcomes before and after the introduction of ART using a large data set from the National Health Laboratory Service. This is the first study to produce estimates of the impact of the ART rollout by exploiting staggered timing and geographic variation in the rollout. After ART became available in a health facility, 3.7% (P < 0.0001) more patients were tested for TB and 3.2% (P < 0.0001) more received repeat testing; however, there was a steep rise in testing before the introduction of ART. Although the number of TB-positive patients increased by 4.3% (P = 0.0002) in the first year post-ART, the TB rate among tested patients fell by 2 percentage points (8%, P = 0.001) after 2 years. Sputum smear testing declined relative to more technologically advanced diagnostics post-ART. Antiretroviral therapy availability increased the attention to TB screening and drew new patients into the health-care system. Small increases in the numbers of repeat patients are indicative of retention in care. The decline in TB rates post-ART suggests that the reduction in TB risk due to improved immune functioning and health-care contact likely outweighed the increased TB risk because of the longer lifespan of ART initiators.

Figure 1.

Number of patients tested for tuberculosis (TB) during quarters before (δ coefficients from equation 1) and after (γ coefficients from equation 1) antiretroviral therapy (ART) introduction relative to time = 0. Time (quarter) is calculated as quarter of observation minus quarter of ART introduction. Dotted lines indicate facility-clustered, heteroskedasticity-robust 95% confidence intervals (all TB tests N = 10,039, time 0 = 953; Repeat TB tests N = 5,098, time 0 = 42; TB tests in hospitals N = 5,268, time 0 = 193; TB tests in clinics N = 5,220, time 0 = 106). This figure appears in color at www.ajtmh.org.

Figure 2.

Number of tuberculosis (TB)-positive patients tested for TB during quarters before (δ coefficients from equation 1) and after (γ coefficients from equation 1) antiretroviral therapy (ART) introduction relative to time = 0. Time (quarter) is calculated as quarter of observation minus quarter of ART introduction. Dotted lines indicate facility-clustered, heteroskedasticity-robust 95% confidence intervals (All TB tests N = 10,039, time 0 = 215; Repeat TB tests N = 5,098, time 0 = 15). This figure appears in color at www.ajtmh.org.

Figure 3.

Proportion of tuberculosis (TB)-positive patients among patients tested for TB during quarters before (δ coefficients from equation 1) and after (γ coefficients from equation 1) antiretroviral therapy (ART) introduction relative to time = 0. Time (quarter) is calculated as quarter of observation minus quarter of ART introduction. Dotted lines indicate facility-clustered, heteroskedasticity-robust 95% confidence intervals (All TB tests N = 10,039, time 0 = 24%; Repeat TB tests N = 5,098, time 0 = 30%). This figure appears in color at www.ajtmh.org.

Figure 4.

Proportion of tuberculosis (TB) tests performed by sputum smear, culture and PCR among patients tested for TB during quarters before (δ coefficients from equation 1) and after (γ coefficients from equation 1) antiretroviral therapy (ART) introduction relative to time = 0. Time (quarter) is calculated as quarter of observation minus quarter of ART introduction. Dotted lines indicate facility-clustered, heteroskedasticity-robust 95% confidence intervals. N = 10,039 (Sputum smear time 0 = 79%, culture time 0 = 19%, PCR time 0 = 1%). This figure appears in color at www.ajtmh.org.

Figure 5.

Proportion of patients tested for tuberculosis (TB) who were female estimated during quarters before (δ coefficients from equation 1) and after (γ coefficients from equation 1) antiretroviral therapy (ART) introduction relative to time = 0. Time (quarter) is calculated as quarter of observation minus quarter of ART introduction. Dotted lines indicate facility-clustered, heteroskedasticity-robust 95% confidence intervals (All TB tests N = 10,039, time 0 = 53%; Repeat TB tests N = 5,098, time 0 = 50%). This figure appears in color at www.ajtmh.org.