Feb. 4, 2000 CHAPEL HILL -- AIDS patients may be at significantly greater risk of death when cytomegalovirus, CMV, circulates in their blood, new research at the University of North Carolina suggests.
The new findings will be presented in San Francisco Wednesday February 2 at the 7th Conference on Retroviruses and Opportunistic Infections. An issue raised by the study is whether or not people infected with HIV, especially those not benefiting from potent anti-retroviral therapy, should receive preemptive treatment with drugs against CMV, according to David Wohl, M.D., assistant professor of medicine, division of infectious diseases, at UNC-CH School of Medicine.
"CMV continues to be a severe opportunistic infection among persons with AIDS," he said. "It used to be devastating in this population. In 85% of these patients it involved the retina and often resulted in blindness."
Antibodies to CMV, a member of the herpes family of viruses, are estimated to occur in at least 60% of the adult population, indicating previous exposure to the virus. When active, CMV is more likely to cause end-organ disease in those with impaired immunity, including people with HIV and the elderly.
According to Wohl, an estimated 90 percent of AIDS patients at UNC have evidence of CMV exposure. "For men who have sex with men it's almost 100%." He notes that the recent decrease in CMV disease among AIDS patients is associated with the advent of newer HIV therapies. "But even with that decrease, some people still have CMV circulating in their blood. We wanted to see what the association was between having CMV in the blood and developing CMV disease or death from any other cause."
Using a variety of CMV tests, including several genetic assays, Wohl and his study collaborators determined that roughly one-quarter of HIV patients they tested at the UNC-NIH AIDS Clinical Trials Unit had CMV in their blood (CMV viremia). This cohort of 157 patients was followed-up for a median of two years.
When detected by one of the more sensitive tests (the CMV DNA PCR), a positive result for CMV in the blood was linked with an 11-fold increased risk of death.
"This test is different from other tests in that it looks for virus circulating in the blood outside the cells," Wohl explained. "That may be more meaningful than finding virus that's sequestered or hiding latent in some cells." The infectious disease specialist believes that CMV circulating in the blood may "rev up HIV, like throwing gasoline on a fire. And as a result you have people having a harder time who otherwise might have gained more control of their HIV infection."
The mainstays of current treatment for CMV involve intravenous injections of highly toxic antiviral drugs such as gancyclovir. These chemotherapies are toxic mainly to bone marrow and kidneys. However, according to Wohl, there is a treatment for eye infection that is more localized to that organ and without the systemic toxicity. It involves an ocular implant of gancyclovir pellets that slowly release the drug over 8-months. Wohl also notes that a potent oral version of gancyclovir may soon be available.
"In diverse clinic populations such as ours, a large component of patients have not benefited from HIV therapy, including those who choose not to accept treatment. Among the questions calling for more study are whether we should screen for CMV viremia in all AIDS patients, and will it be worthwhile to administer preemptive therapy to those who test positive?"
Along with Wohl, study collaborators from UNC are Susan Fiscus, Charles van der Horst, Jean Handy, William Pan, and David Rosen.
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