Tuberculosis risk before and after highly active antiretroviral therapy initiation: does HAART increase the short-term TB risk in a low incidence TB setting?

To evaluate the short-term and long-term effects of highly active antiretroviral therapy (HAART) on tuberculosis (TB) risk compared with risk without HAART in a low TB incidence setting.

An observational cohort study among HIV-infected persons in care at the Comprehensive Care Center (Nashville, TN) between January 1998 and December 2008.

A marginal structural model was used to estimate the effect of HAART on short-term (≤180 days) and long-term (>180 days) TB risk, with CD4⁺ lymphocyte count incorporated as a time-updated covariate.

Of 4534 HIV-infected patients, 34 developed TB (165 per 100,000 person-years; 20,581 person-years of follow-up). Seventeen cases occurred among persons not on HAART or >30 days after HAART discontinuation (212 per 100,000 person-years; 8019 person-years of follow-up). Seventeen occurred among persons on HAART (135 per 100,000 person-years; 12,562 person-years of follow-up); 10 in the first 180 days (402 per 100,000 person-years; 2489 person-years of follow-up); and 7 after more than 180 days (69 per 100,000 person-years; 10,073 person-years of follow-up). After adjusting for the most recent CD4⁺ lymphocyte count, the risk of TB in the first 180 days of HAART exposure relative to no HAART was 0.68 (0.14-3.22, P = 0.63).

In this low TB incidence setting, the TB rate in the first 180 days of HAART was almost twice as high as persons not on HAART. However, after adjusting for most recent CD4⁺ count, there was no significant difference in TB risk between these 2 groups. This suggests that low recent CD4⁺ lymphocyte count influences TB risk during the first 180 days of HAART.