TB role in HIV disease gaining clarification

Importance of preventive therapy underscored

Several new studies on the impact of TB on HIV-positive patients help clarify the cause of rapid acceleration of the virus and underscore the importance of preventive TB therapy.

French researchers, studying 620 AIDS patients, found that length of survival was significantly shorter in 120 patients also infected with TB. The difference in survival was found despite the fact that TB did not appear to reduce CD4 count or increase the occurrence of opportunistic infection, according to an article published in the latest issue of the American Journal of Epidemiology.

The decline in survival was so strong that the authors state that TB may be a marker of advanced HIV, and "is a strong predictor of mortality, particularly in patients with CD4 counts of fewer than 200 cells. These findings provide an additional argument for greater use of tuberculosis preventive therapy in HIV-infected patients."

Half of NYC patients lost to follow-up

While TB preventive therapy has become more widespread in high-risk cities, a study presented by researchers from the Centers for Disease Control and Prevention at the Fourth Conference on Retroviruses and Opportunistic Infections in Washington, DC, found that completion rates in New York City were often compromised because nearly half of patients were lost to follow-up care. The researchers called for better strategies to ensure coordination of care and completion of preventive therapy.1

For several years now, researchers have known that tuberculosis increases replication of HIV. A new study, also presented at the conference, has gone a step further and shown that the activation of HIV is associated with high levels of pro-inflammatory cytokines, such as interleukin-10, tumor necrosis-alpha, and interleukin-6. Finding ways to suppress these cytokines may be useful in treating co-infected patients, they say.

"The delicate balance between pro-inflammatory and anti-inflammatory cytokines plays a major role in HIV replication induced by a common pathogen such as TB," says Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases in Bethesda, MD.

Suppressive cytokines block TB-induced HIV

NIAID researchers, lead by Delia Goletti, MD, PhD, a former NIAID researcher now working in Italy, found that when you add suppressive cytokines — interleukin-10 and transforming growth factor-beta — TB-induced increase in HIV replication can be blocked. These cytokines appear to inhibit the virus by blocking the activity of pro-inflammatory cytokines and by diminishing the proliferation and activation of HIV-infected cells.2

"Earlier, Goletti showed that for HIV-positive people who had TB, their viral load went up 20-fold during active TB," says Drew Weissman, MD, MPH, a senior fellow at NIAID. "Now we are trying to understand what regulates the virus. It appears that during TB disease cytokines are released, and if you can inhibit them, you can regulate viral replication."

How cytokines can be regulated in vivo is the next step in the research, he says. One potential blocker of proinflammatory cytokines is thalidomide, but so far the drug has not been shown to be effective, Weissman says.

References

1. Sackoff J, Torian L, Vavagiakis P, et al. TB preventive therapy in HIV-infected persons. Presented at the Fourth Conference on Retroviruses and Opportunistic Infections. Abstract # 648. Washington, DC; 1997.

2. Goletti D, et al. Exogenous and endogenous anti-inflammatory cytokines IL-10 and TGF-beta inhibit tuberculosis-induced HIV replication in CD8-depleted peripheral blood mononuclear cells from HIV-infected individuals. Presented at the Fourth National Conference on Retroviruses and Opportunistic Infections. Abstract # 121. Washington, DC; 1997.