A Deadly Synergy
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Christopher Whalen, M.D.
Credit: Dr. Whalen |
Tuberculosis weighs heavily upon the world and the poorest among us bear most of the burden. More than 80 percent of TB cases worldwide arise in only 22 countries, most of which are poor. Where malnutrition, substandard housing, and minimal health care are common, so too is TB. And where TB significantly impairs the health of many workers, entire economies are weakened.
The global crisis demands a global response. For decades, NIAID has supported research aimed at improving global health by lessening the burden of infectious disease. Key elements of NIAID’s global health research plan include
- Disease prevention and treatment strategies adapted to specific needs of developing countries
- Sustained development of individual countries’ research capacities
- Stimulation of scientific collaboration among individual researchers and initiation of partnerships among governmental and nongovernmental organizations.
When someone is infected with both Mycobacterium tuberculosis (M. tb), the organism that causes TB, and HIV, the virus that causes AIDS, the combination produces a deadly synergy that makes both diseases more destructive together than either is alone. Nowhere is this terrible synergy more apparent than in Africa where, according to the World Health Organization (WHO), TB cases are increasing 10 percent each year in the wake increasing levels of HIV infection. In October, 2004, the WHO estimated that some 8 million Africans were co-infected by HIV and M. tb.
“We must achieve a better understanding of the HIV/AIDS-TB interaction so that African nations can make headway in controlling both these diseases,” says Christopher Whalen, M.D., of Case Western Reserve University in Ohio.
While the exact mechanisms involved in the twin disease processes in people infected by both M. tb and HIV are unknown, it is possible that immune system chemicals released to fight reactivated TB also spur HIV replication, thus speeding the debilitating effects of AIDS.
In collaboration with Ugandan scientists in Kampala, Dr. Whalen is conducting clinical trials in HIV-positive people who are co-infected with TB. The overall aim of the research is to learn what mechanisms drive TB and HIV interactions.
One clinical trial tested the theory that a normal, robust immune response to TB infection has the undesirable effect of revving up the replication of HIV. The scientists gave trial participants a form of the common anti-inflammatory drug prednisone to blunt immune system activity against TB. They hoped the inexpensive drug would prevent TB reactivations. Although they could inhibit immune system activity that otherwise would spur on TB, the scientists also saw a rise in the amount of HIV circulating in the participants’ blood. This finding, and the fact that prednisone is too toxic to give on a long-term basis, leads Dr. Whalen to believe that steroids like prednisone will not typically be part of the TB- and HIV-fighting arsenal for most co-infected individuals. Nevertheless, he adds, immune system modulators of some kind probably will pay dividends in improved health for those infected with both M. tb and HIV.
In 2005, Dr. Whalen and his co-investigators in Uganda began enrolling patients in a new clinical trial. The scientists will test whether it is possible to delay the onset of full-blown AIDS in HIV-TB co-infected individuals by providing volunteers with antiretroviral drugs (that work against HIV) simultaneously with the normal 6-month-long regimen of TB drugs. As Dr. Whalen notes, if a course of antiretroviral drugs given before full-blown AIDS develops keeps HIV levels low enough that co-infected people can perform normal activities, the burden on the community’s healthcare systems would be lightened. In addition to answering basic scientific questions about the interactions between HIV and M. tb, the Uganda trial could also help clinicians more effectively treat HIV-TB co-infected people.
“It’s important to continue to study HIV/AIDS and TB,” notes Dr. Whalen, “because the better we are at containing HIV, the better will become at containing TB. There will certainly be positive effects on both epidemics.”
References
Mayanja-Kizza, H. et al. Immunoadjuvant prednisolone therapy for HIV-associated tuberculosis: A phase 2 clinical trial in Uganda. J Infect Dis. 2005 Mar 15;191(6):856-65. Epub 2005 Feb 8.
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