How Soon after Infection with HIV Does the Risk of Tuberculosis Start to Increase? A Retrospective Cohort Study in South African Gold Miners

Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, UK.
The Journal of Infectious Diseases (Impact Factor: 6). 02/2005; 191(2):150-8. DOI: 10.1086/426827
Source: PubMed


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.
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.
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.
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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Available from: Pam Sonnenberg
    • "In the recent times, AIDS epidemic has had an immense bearing on the clinical presentation, transmission and epidemiology of TB worldwide (Pawlowski et al., 2012). TB is predominantly caused by the pathogenic mycobacteria M. tuberculosis; however, non-tuberculous or attenuated strains of mycobacteria such as Mycobacterium avium, Mycobacterium kansasii, Mycobacterium fortuitum, Mycobacterium xenopi and Mycobacterium bovis Bacillus Calmette– Guérin (BCG) cause opportunistic infections in HIV patients (Juffermans et al., 1998; Smith et al., 2001; Bachmeyer et al., 2002; Karakousis et al., 2004; Serra et al., 2007; Singh et al., 2007; Azzopardi et al., 2009; Hesseling et al., 2009) even before T-cell depletion is apparent (Sonnenberg et al., 2005). More than 90 species of Mycobacterium had been reported to inhabit natural (air, water, soil or other organisms) and artificial (chlorinated municipal water) reservoirs (Primm et al., 2004). "
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    ABSTRACT: Environmental mycobacteria, highly prevalent in natural and artificial (including chlorinated municipal water) niches, are emerging as new threat to human health, especially to HIV infected population. These seemingly harmless non-pathogenic mycobacteria, that are otherwise cleared, establish as opportunistic infections adding to HIV associated complications. Though immune-evading strategies of pathogenic mycobacteria are known, the mechanisms underlying the early events by which opportunistic mycobacteria establish infection in macrophages and influencing HIV infection are unclear. Proteomics of phagosome-enriched fractions from M. bovis BCG mono- and HIV-M. bovis BCG co-infected THP-1 cells by LC-MALDI-MS/MS revealed differential distribution of 260 proteins. Validation of the proteomics data showed that HIV co-infection helped the survival of non-pathogenic mycobacteria by obstructing phagosome maturation, promoting lipid biogenesis and increasing intracellular ATP equivalents. In turn, mycobacterial co-infection up regulated purinergic receptors in macrophages that are known to support HIV entry, explaining increased viral titers during co-infection. The mutualism was re-confirmed using clinically relevant opportunistic mycobacteria, M. avium, M. kansasii and M. phlei that exhibited increased survival during co-infection, together with increase in HIV titers. Additionally, the catalogued proteins in the study provide new leads that will significantly add to the understanding of the biology of opportunistic mycobacteria and HIV coalition. This article is protected by copyright. All rights reserved.
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    • "The main feature of immunosuppression in AIDS patients is the manifest loss of CD4 þ T cells, in the blood, lymphoid tissues, and mucosa, which is obviously an important contributor to the increased risk of developing active TB (Moir et al. 2011). However, susceptibility to TB increases soon after HIV infection, far before the decrease of the CD4 þ T-cell counts below 500 cells/mL (Sonnenberg et al. 2005), clearly showing that the mechanisms underlying the increased susceptibility of HIV-infected individuals to active TB goes beyond the CD4 þ T-cell drop. In fact, the World Health Organization (WHO) recommends the initiation of antiretroviral therapy for any HIV-infected individual who develops TB, regardless of the CD4 þ T-cell counts (WHO 2013). "
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    • "Around the world, people living with HIV have a 20-fold higher risk than people without HIV of dying from tuberculosis (TB) [1]. Active TB disease can occur at any stage of HIV infection [2], [3] and, as such, routine screening for TB during HIV care provides important opportunities to prevent, diagnose, and promptly treat the disease. Given the vulnerability of people living with HIV, prevention is especially important. "
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