The effect of HIV in a general population

The effect of HIV in a general population cohort in Malawi.

The aim of the study was to estimate rates of recurrent tuberculosis due to reinfection and relapse, by HIV status, in a general population. A long-term cohort study was conducted in Karonga district, rural Malawi. All tuberculosis patients with culture-proven disease in Karonga district were followed up after treatment. HIV testing was offered and all Mycobacterium tuberculosis isolates were fingerprinted using IS6110 RFLP. Fingerprints from initial and recurrent disease episodes were compared to distinguish relapse and reinfection: a second episode was considered a relapse if the fingerprint was identical or differed by only 1-4 bands and was the first occurrence of that pattern in the population. Rates of and risk factors for recurrence, reinfection disease, and relapse were estimated using survival analysis and Poisson regression. Five hundred and eighty-four culture-positive episodes of tuberculosis were diagnosed and treatment was completed during 1995-2003 in patients with known HIV status; 53 culture-positive recurrences occurred by May 2005. Paired fingerprints were available for 39 of these. Reinfections accounted for 1/16 recurrences in HIV-negative and 12/23 in HIV-positive individuals. Rates of relapse were similar in HIV-positive and HIV-negative individuals. Using multiple imputation to allow for missing fingerprint information, the rate of reinfection disease in HIV-positive individuals was 2.2/100 person-years, and in HIV-negative individuals 0.4/100 person-years. HIV increases the rate of recurrent tuberculosis in this setting by increasing the rate of reinfection disease, not relapse.

It appears from this and other studies that a second bout of tuberculosis (TB) in an HIV-negative person in most settings is most likely to be due to relapse and may reflect overall programme effectiveness in treating TB. Relapse rates following successful completion of treatment are highest in the first 6 months off treatment. Although numbers were small, relapse rates in this study were encouragingly similar for HIV-negative and HIV-positive people. The story was much different for re-infection with a rate ratio of 6.3 (1.3-31.5, p=0.02) comparing HIV-positive and HIV-negative individuals. That re-infection occurs at all among HIV-negative people begs the question: if natural infection does not always prevent re-infection, is there still hope for a TB vaccine, at least for some people? The higher risk of re-infection in HIV-positive people, none of them on antiretroviral treatment, suggests that HIV may directly influence the risk of re-infection, increase the risk of development of disease, and/or increase the risk of exposure to other TB strains in health care settings. It is important to untangle the contribution of each of these and to see if antiretroviral treatment scale-up to all HIV-positive patients with TB, along with environmental controls in TB and HIV clinics, can reduce the risk of re-infection and associated high mortality for people living with HIV.