United Press International - Wednesday, October 14, 1998
Lori Valigra

Further, the researchers say, the different viruses seem to react differently to antiviral AIDS therapies,

This means it may no longer be sufficient to test for and treat viruses in the bloodstream of HIV carriers; the virus must also be identified and treated in semen. The discovery may lead to new strategies for treating AIDS.

The research, conducted at the University of North Carolina at Chapel Hill and St. Gall Cantonal Hospital in Switzerland, appears in the Oct. 22 issue of the AIDS journal, which is published in London. The work was supported by the U.S. National Institutes of Health, the Swiss National Science Foundation and others.

"This study is further evidence of the compartmentalization of HIV. It reinforces our concern about the persistence of virus reservoirs, even in the face of what would appear to be effective antiviral therapies," said Dr. Oren Cohen, assistant director for science policy at the National Institute of Allergy and Infectious Diseases of the NIH in Bethesda, Md.

Earlier studies used different measurement techniques and a more limited number of patients. Cohen said other studies indicate a similar situation exists in female blood and vaginal secretions.

The researchers studied blood and semen samples from 11 volunteers for three years. The volunteers had HIV-1 (a strain of the AIDS virus prevalent in western, industrialized nations) and they were on antiviral therapy. The researchers focused on special parts of the genetic makeup of the virus (reverse transcriptase and protease RNA) for the development of resistance to antiretroviral therapy. The HIV virus changes, or mutates, quickly as it replicates itself inside the body. The scientists looked for mutations of the virus that are resistant to AIDS drugs.

They found that the viruses of eight of the 11 volunteers had some sort of resistance in the blood and/or semen to one or another of the antiviral agents used as AIDS medications. In addition, they found that two of the patients whose blood viruses were resistant to anti-AIDS protease inhibitor drugs had semen viruses that did not develop such resistance. Protease inhibitors either did not penetrate the male reproductive organs or did so with great difficulty, the researchers said.

Another patient showed AZT resistance in his semen HIV viruses, and only later in his blood viruses.

The researchers said their wotk provides further evidence to previous studies that male reproductive organs and the bloodstream act as virtually independent compartments that may have to be dealt with separately when giving AIDS therapy. The viruses in the two compartments may not be attacked by drugs in the same way.

Drugs act in different concentrations and for different periods of time when absorbed into different parts of the body, said Dr. Myron Cohen, co-author of the AIDS study and chief of the division of infectious diseases at the University of North Carolina's department of medicine. This may result in different versions of the virus.

"When you take antiviral drugs, resistance can develop and the resistance mutations of the virus can be different in the blood than in the semen," Cohen said. "Drugs must be developed to eliminate HIV from both."

The researchers said their work may have substantial consequences for newly infected individuals and for public health. "Therapeutic strategies that fully suppress HIV-1 in the genital tract should be a public health priority," they wrote in the AIDS journal.

The authors are advocating therapeutic strategies that attack both the blood and semen HIV viruses, because HIV still is transmitted chiefly through unprotected sexual intercourse. They also said further study is needed to understand how much antiviral drug gets into the genital tract and how much virus it kills.

The danger, said Cohen of the University of North Carolina, is that a drug-resistant version may be transmitted to another person, lessening the effectiveness of antiviral drugs in that newly infected person.

Cohen of the National Institute of Allergy and Infectious Diseases said the study is a sober realism that drugs are not perfect. Said Cohen, "This was an anticipated result."

One future possibility, he said, is new drugs that specifically target each pocket of the virus in the body.

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