Oct. 16, 1998 CHAPEL HILL -- A study by the University of North Carolina at Chapel Hill confirms the presence of mutated, drug-resistant human immunodeficiency virus in the semen of men taking antiviral medications for HIV infection.
A report of the study, to appear Oct. 22 in the journal AIDS, carries important personal and public health implications for treating and controlling the spread of the disease, according to Dr. Joseph J. Eron, lead author and associate professor of medicine at the UNC-CH School of Medicine.
"This paper is important because it clearly documents that sexual fluids or genital secretions do contain resistant virus, so the fear that there is some spread of resistant HIV is founded on logical scientific evidence," he says.
The mutated HIV strains include those less susceptible to suppression by a spectrum of front-line AIDS medications including ziduvodine (ZDV), didanosine (ddi), and lamivudine (3TC) .
Eron, a UNC infectious disease specialist, points to a case report last summer in The New England Journal of Medicine of infection with a strain of HIV that was resistant to multiple antiviral medications. "Our study shows how this can happen," he says. "It is also the first to demonstrate that if men, and presumably women, do not have adequate suppression of their virus, as measured by levels of the virus in their blood, they are very likely to shed drug-resistant strains of HIV in their genital secretions. And that is virus that's available for transmission."
Previous research at Carolina and other centers has shown that effective treatment with a potent "cocktail" of antiviral medications typically is associated with suppression of the virus both in blood and semen to below detectable levels. "But the men studied in this new report continued to have detectable virus within their blood and semen, even in the face of what we intended to be effective therapy. These men shed resistant virus and the virus became more resistant over time," Eron says.
The new study focused on 11 HIV-infected men in North Carolina and Switzerland, most with a history of having sex with men, but not exclusively. Five of the 11 had never taken drugs for HIV. Six had received previous treatment with reverse transcriptase (RT) drugs, which are designed to block HIV from delivering its DNA into the cell. All subjects were identified with detectable levels of the AIDS virus both in their blood and semen when the study began.
At the beginning of the study and periodically up to 58 weeks, the researchers measured the amount of HIV in the men's blood and semen while they received a new program of antiviral therapy. The therapy included a variety of antiviral AIDS drugs. "And what we showed was that men who had previous treatment already had evolved virus in their blood and genital tract that contained mutations known to decrease the susceptibility of that particular virus strain to the available drugs," Eron explains.
Moreover, when men with drug-resistant HIV in blood and semen were followed over time, "they continued to acquire higher levels of resistance while receiving antiviral therapy," Eron says.
Three of the six patients with previous RT experience showed evidence of RT-resistant HIV in their semen and continued to do so as treatment went on. And eight of 10 whose HIV was genetically analyzed as the study continued showed "new resistance mutations" in their blood or semen or both.
"We need to emphasize not only for personal health, but for public health, that the goal of treatment should be to get the virus to immeasurable levels, both in the blood and other biological compartments, specifically the genital tract," Eron says. "We also need to understand more about our drugs. In other words, do our drugs get into the genital tract both in men and women? Is there some block to that, and are they getting in at levels high enough to suppress the virus? The better we understand these issues, the better we'll be at trying to prevent the spread HIV."
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