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How soon after infection with HIV does the risk of tuberculosis start to increase? A retrospective cohort study in South African gold miners.
Sonnenberg P, Glynn JR, Fielding K, Murray J, Godfrey-Faussett P, Shearer S.
J Infect Dis
2005 Jan 15;191(2):150-8.
Abstract
BACKGROUND: Infection with human immunodeficiency virus (HIV) increases the risk of tuberculosis (TB), but no study has assessed how this risk changes with time since HIV seroconversion. METHODS: The incidence of pulmonary TB was estimated in miners with and those without HIV infection in a retrospective cohort study. HIV test results were linked to routinely collected TB, demographic, and occupational data. The rate ratio (RR) for the association between HIV status and TB was estimated by time since HIV seroconversion, calendar period, and age. RESULTS: Of the 23,874 miners in the cohort, 17,766 were HIV negative on entry, 3371 were HIV positive on entry, and 2737 seroconverted during follow-up (1962 had a seroconversion interval of < or =2 years). A total of 740 cases of TB were analyzed. The incidence of TB increased with time since seroconversion, calendar period, and age. TB incidence was 2.90 cases/100 person-years at risk (pyar) in HIV-positive miners and was 0.80 cases/100 pyar in HIV-negative miners (adjusted RR, 2.9 [95% confidence interval {CI}, 2.5-3.4]). TB incidence doubled within the first year of HIV infection (adjusted RR, 2.1 [95% CI, 1.4-3.1]), with a further slight increase in HIV-positive miners for longer periods, up to 7 years. CONCLUSION: The increase in the risk of TB so soon after infection with HIV was unexpected. Current predictive models of TB incidence underestimate the effect of HIV infection in areas where TB is endemic.
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Reviewed by
Susa Coffey, MD
Comment
It is well appreciated that HIV infection greatly increases the risk of developing tuberculosis (TB). While the risk of TB increases substantially with declining immune status, even HIV-infected persons with relatively high CD4 cell counts have significantly higher risk of tuberculosis than HIV-uninfected persons. In people recently infected with HIV, however, the incidence of TB generally has been assumed to be relatively low, and large, well-controlled studies to define the risk of TB in recent HIV infection had not been performed.
This study, a retrospective analysis of the incidence of TB in a large cohort (n=24,874) of South African gold miners with recent HIV seroconversion, determined that
the risk for developing pulmonary TB increased very soon after HIV infection: it doubled in the first year and increased by four times by 2 years
. Several sensitivity analyses performed to take into account various possible confounders showed similar increases in the risk of pulmonary TB in the first year after seroconversion, with the risk continuing to increase in the following years.
This surprising finding begs the question of why vulnerability to pulmonary TB increases so soon after infection with HIV, at a time when CD4 count numbers generally are relatively high. The editorial that accompanies this article speculates on the possible reasons, including early immune system dysregulation due to HIV infection, and rapid progression of HIV disease.(1) Both the article and the editorial briefly address the provocative implications of this study for TB prevention in HIV-infected people.
Taken together, this article, the accompanying editorial, and a related review of immune responses to TB give an excellent overview of current understanding of the interactions of TB and HIV infection.(2)
See also
Lawn, Bekker, Wood
References
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