Recurrent Tuberculosis Risk Among HIV-Infected Adults in Tanzania With Prior Active Tuberculosis

Heimbeck reported in 1930 that student nurses in Oslo with latent tuberculosis infection before starting work in a tuberculosis hospital had a decreased risk of subsequent active tuberculosis compared with classmates with a negative baseline skin test [1]. More recently, Andrews and colleagues estimated that individuals with latent tuberculosis who were newly tuberculosis exposed had a 79% lower risk of active tuberculosis compared to subjects without prior latent tuberculosis [2]. These studies indicate that among immunocompetent persons, latent tuberculosis infection without progression to active tuberculosis is associated with protection from subsequent active tuberculosis on reexposure. In contrast, subjects who have developed active tuberculosis disease once and then have been successfully treated exhibit a 4-fold increased risk of subsequent tuberculosis disease [3]. Taken together, these data in human immunodeficiency virus (HIV)–negative subjects show that although immunologic protection against tuberculosis is generated by infection that does not progress to tuberculosis, persons who fail to contain tuberculosis infection once are at risk to develop active tuberculosis. HIV infection increases the overall risk of active tuberculosis disease developing after latent tuberculosis infection with a risk of active tuberculosis disease ranging from 3.7 to 16.2 cases per 100 years [4–9]. The risk of active tuberculosis also appears to be increased by a prior episode of active tuberculosis: a study in HIV-infected South African miners with at least 1 episode of active tuberculosis showed that the risk of subsequent active tuberculosis disease was 19.7 cases per 100 years compared with 3.7 cases per 100 years among a similar but distinct cohort of HIV-infected miners without known prior active tuberculosis [9]. However, to our knowledge, no studies among HIV-infected adults have compared the incidence of subsequent active tuberculosis between subjects with and without prior active tuberculosis in a single cohort to calculate of the impact of prior active tuberculosis on the hazard of subsequent tuberculosis. The DarDar Trial was a 7-year, randomized placebo-controlled phase 3 efficacy trial of a novel tuberculosis booster vaccine in HIV-infected adults [10]. At baseline, 80 (8.2%) subjects reported treatment for prior active tuberculosis. Here we evaluate the hazard of subsequent active tuberculosis among DarDar Trial placebo recipients with and without prior active tuberculosis.