Jefferson Scientists Find Evidence Of Potentially Infectious HIV In Semen, Despite Inability To Detect Active Virus In Blood

December 16, 1998

Can the AIDS virus still be dangerous even if it can't be detected in the body?

Apparently so. Scientists at Jefferson Medical College have found that the AIDS virus, HIV, is still present in an inactive 'latent'--and potentially infectious--form in the semen of infected men undergoing treatment with powerful, new antiretroviral therapies, even if no measurable virus can be detected in the blood.

"It suggests that even if you don't have detectable virus in your blood and are on highly active retrovirals, you should consider yourself potentially contagious sexually and practice safe sex," says Roger J. Pomerantz, M.D., professor of medicine, biochemistry and molecular pharmacology, and chief of the division of infectious diseases at Thomas Jefferson University in Philadelphia, who led the work.

The researchers report their findings Dec. 17 in The New England Journal of Medicine.

"It suggests that potential eradication of the virus may be hampered by this finding," says Dr. Pomerantz, who also directs Jefferson's Center for Human Virology. "Some scientists have suggested that if you give enough and proper drugs to a patient, you can eradicate the virus. That still may be possible--we don't know enough yet."

Dr. Pomerantz and his colleagues examined seven men, all of whom were taking highly active antiretroviral therapy (HAART)--a combination therapy of protease and reverse transcriptase inhibitors--and who had no detectable virus in their blood or seminal fluid for several months.

Last year, three research groups at the University of California, San Diego, Johns Hopkins University and the National Institute of Allergy and Infectious Diseases showed that patients taking HAART have latently infected immune system T-cells in the blood. "We asked, could it happen in seminal fluid and could this be from the trafficking of cells from the blood?," he says.

Using a powerful molecular technique, polymerase chain reaction, he and his co-workers found HIV provirus--a precursor form of HIV--in the semen of four of the seven men.

"The question was, is it defective virus or is it replication competent?" he says. In two of the four cases in which HIV provirus was found in the semen, the scientists subsequently grew HIV in the laboratory by mixing provirus-containing cells with uninfected blood cells. This result suggests that provirus cells may be able to develop into infectious virus, Dr. Pomerantz says.

The Jefferson team's results reinforce recommendations by the Centers for Disease Control and Prevention (CDC). That is, all HIV-infected individuals, even those taking HAART and who have no measurable virus in their blood, should continue practicing safe sex and other behaviors aimed at preventing transmission of the virus.

The researchers found that the viruses are macrophage-tropic--they infect macrophages, white blood cells affected by HIV infection. These are the virus types that can be transmitted sexually. "We looked if there were resistance mutations for all of these drugs--reverse transcriptase and protease inhibitors. We found no resistance markers, suggesting that these viruses may be latent in the cell as integrated provirus, and have probably been there since the time of infection." Still, low levels or tiny bursts of viral replication could be occurring in small regions of the male genital tract.

Dr. Pomerantz explains, "Even if you inhibit all of the actively replicating virus in actively producing cells, you still have provirus in the blood and now we know in the semen, lying in wait."

The researchers aren't sure yet whether or not the provirus is transmissible.

Dr. Pomerantz plans to next look at infected women on HAART who have no detectable virus in their blood and see if they also harbor these infected cells in genital secretions. The researchers also plan to test 'discordant partners'--infected men and their uninfected partners--to see if those on HAART who may not be using safe sex can transmit virus to their partners.

Thomas Jefferson University

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