Background:  Although the risk of tuberculosis (TB) among HIV-infected individuals decreases greatly during the first 1 to 2 years of HAART, it remains substantially higher than the risk among individuals without HIV. As a result, modeling calculations have estimated that HAART may have little effect on TB incidence rates in low-income countries. However, we hypothsized that TB incidence rates may continue to decrease during long-term HAART and that modifiable risk factors for TB during HAART may also exist.

Methods:  Microbiologically or histologically confirmed cases of incident TB were identified in a prospective hospital-based cohort of 346 patients receiving HAART between 1996 and 2005 in Cape Town, South Africa.

Results:  During 1107 person-years of observation, 27 cases of incident TB occurred. The TB incidence density rate was 3.5 cases/100 person-years in the first year and significantly decreased during follow-up (p trend = 0.002), reaching a rate of 1.01 cases/100 person-years in the fifth year of treatment. TB incidence was highest among patients with baseline CD4 cell counts <100 cells/uL and those with World Health Organization (WHO) clinical stage 3 or 4 disease (5.71 and 3.88 cases/100 person-years, respectively). Risk of TB was independently associated with CD4 cell count <100 cells/mL (adjusted risk ratio [ARR] = 2.38; 95%CI 1.01 to 5.60; p = 0.04), WHO stage 3 or 4 disease (ARR = 3.60; 95%CI 1.32 to 9.80; p = 0.01), and age <33 years (ARR = 2.86; 95%CI 1.29 to 6.34; p = 0.01). Risk of TB was not independently associated with plasma viral load, previous history of TB, low socioeconomic status or sex. Despite similar virological responses to HAART, blood CD4 cell count increases were much smaller among patients who developed TB compared to those who remained TB-free.

Conclusions:  TB incidence continued to decrease during the first 5 years of HAART, with a 3.5-fold reduction occurring beyond the first year of treatment. HAART may therefore contribute more to TB control in low-income countries than has previously been estimated. Patients with advanced pre-treatment immunodeficiency had persistently increased risk of TB during HAART and TB occurred among those with poor immunological recovery during HAART. Advanced immunodeficiency among patients accessing HAART in low-income countries may limit immune recovery and lead to chronically heightened risk of TB.