Implications of the Increased Risk of Tuberculosis (TB) During the Course of HIV Infection

The increased risk of tuberculosis (TB) early during the course of HIV infection has several important implications for predicting the impact of HIV on the global tuberculosis (TB) epidemic. Following are excerpts from an editorial by Srikantiah and others in the January 15, 2004 Journal of Infectious Diseases (JID) that comments on the implications of the study by Sonnenberg and others appearing in the same issue of JID.

Although it is difficult to generalize the magnitude of the increase in incidence found in this highly specialized population of gold miners and to apply it to the rest of the developing world, it is likely that some significant increase in incidence does occur during the first year after HIV seroconversion.

Although current models that estimate the global burden of TB acknowledge the strong association between TB incidence and adult HIV prevalence, they do not account for the increased risk of TB early during the course of HIV infection. Reframing these models in the context of these new data is likely to affect the calculated burden of TBand not just for HIV-positive persons, but for the general community as well.

The increased risk of TB early during the course of HIV infection also has important implications for the prevention of TB in HIV-positive persons. Potential methods include the use of antiretroviral drugs and chemoprophylaxis for latent TB infection. Data from South Africa suggest that the use of highly active antiretroviral therapy is effective in reducing the incidence of HIV-associated TB in persons with CD4 cell counts <350 cells/L. If persons who develop TB early during the course of HIV infection represent rapid progressors with low CD4 cell counts, then determination of CD4 cell counts may be all that is necessary to identify the subset of persons who are at highest risk.

Alternatively, if most persons who develop TB early during the course of HIV infection have high CD4 cell counts and no indications for antiretroviral therapy, then the treatment of latent M. tuberculosis infection may be the most feasible way to reduce the risk of TB. Data from Uganda suggest that treatment of latent M. tuberculosis infection can provide protection against TB in HIV-positive persons; the duration of protection was lengthened to 3 years by use of treatment regimens that combined isoniazid with rifampicin.

However, defining and implementing optimal preventive therapy for TB in Africa is a challenging endeavor. The optimal duration of treatment and the optimal regimens are unknown and are currently under investigation. Preventive therapy programs also require the exclusion of active TB, which may be difficult in resource-constrained settings.

Perhaps the most immediate and universal implication of these important data from Sonnenberg et al.'s study is the need to expand reliable and affordable HIV testing services in areas where TB is endemic.

The accurate identification of undiagnosed HIV infection is the necessary first step in the implementation of prevention measures that aim to curtail the spread of M. tuberculosis and HIV coinfection. The timely and reliable evaluation of TB in HIV-positive persons is another key component that needs to be further strengthened to curb the epidemic.

The ProTEST initiative that has been established in 3 sub-Saharan African countries by the World Health Organization aims to develop a more coherent response to TB in settings where HIV prevalence is high by combining improved access to high-quality HIV counseling and rapid testing services with intensified screening for TB.

Preliminary reports from these sites indicate that such collaborative efforts between HIV/AIDS and TB control programs are feasible and effective. Improvement of the links between the HIV and TB clinical and public-health services will be critical to effectively handling the challenges of this co- epidemic.

Center for AIDS Prevention Studies, Division of Infectious Diseases, and HIV/AIDS Division, San Francisco General Hospital, University of California at San Francisco, San Francisco.

01/05/05

Reference
P Srikantiah, E Charlebois, and D V Havlir. Rapid Increase in Tuberculosis Incidence Soon after Infection with HIVA New Twist in the Twin Epidemics (editorial). Journal of Infectious Diseases 191(2): 147-149. January 15, 2005.