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University of Pittsburgh Discovery of HIV "Shedding" Patterns and Viral Site Will Change Direction of Research on Aids Vaccines and Treatments

PITTSBURGH, January 30, 2000 — AIDS researchers at the University of Pittsburgh have found that viral secretion in HIV-positive men follows one of three patterns, which are in turn related to different sources of HIV in the body. This discovery, which has important implications for research on vaccines and retroviral therapies, was presented on Sunday, Jan. 30, in a poster session at the Seventh Conference on Retroviruses and Opportunistic Infections in San Francisco.

"For the first time, we see that some HIV-positive men continuously produce, or shed, the virus, and that in this case the virus originates in the blood," said Principal Investigator Phalguni Gupta, Ph.D., professor, department of infectious diseases and microbiology at the University of Pittsburgh Graduate School of Public Health. "Other men shed intermittently, and in them the virus is produced in a genital organ, probably the prostate." Another 28 percent of the participants were found to be non-shedders, meaning that virus was not detected in the semen but could be in the blood. While they are antibody-positive, non-shedders are less likely to infect their partners.

Previous research has shown that some men have the same strain of HIV in their blood and semen, while others exhibit differing strains. "Interestingly, we now see that those with the same strains in blood and semen are continuous shedders, while those with distinct virus populations are intermittent shedders," Dr. Gupta explained.

Investigators studied 18 HIV-infected men from the Pittsburgh site of the national Multicenter AIDS Cohort Study, known locally as the Pitt Men’s Study. Participants were asymptomatic and not receiving any potent antiretroviral therapy, such as protease inhibitors. Paired blood and semen samples were collected at weekly intervals for 10 weeks and tested for viral load. HIV was detected at all 10 visits in the semen of five subjects (28 percent), constituting the continuous shedders. In eight participants (44 percent) HIV was detected intermittently in 15 to 70 percent of all visits – the intermittent shedders. A third group, five subjects (28 percent) exhibited no HIV in semen in any of the 10 visits, and were thus designated non-shedders.

With this new knowledge about compartmentalization of HIV between blood and semen, researchers now know that any vaccine prepared from blood-borne HIV would not be effective against sexual transmission of HIV in all men. In addition, potent retroviral therapy may have a different effect on HIV in semen as compared to that in blood in men who shed the virus intermittently.

"Vaccines and retroviral therapies will need to address multiple HIV strains in intermittent shedders," said Dr. Gupta. "If a man has different strains of HIV in his blood and semen, a drug or vaccine targeted at just one would, of course, have no effect on the other." University of Pittsburgh researchers have therefore begun testing patients who failed antiretroviral therapy to determine if their seminal virus is indeed different from that present in their blood.

Dr. Gupta’s study also found that the compartmentalization of HIV is related to the number of a man’s sexual partners. Continuous shedders with blood-borne virus tend to be men who have multiple sex partners and resulting chronic inflammation of the male genital organ, according to Dr. Gupta. "This inflammation constitutes a leak in the system that allows virus or virus-infected cells in the blood to enter the genital organ, resulting in like strains in both blood and semen," he said.

On the other hand, all non-shedders in the study had only one partner. Intermittent shedders in the study did not show a correlation between number of partners and shedding pattern. The fact that intermittent shedders have different strains of HIV in their semen and blood suggests that the secreted virus is produced by an organ, according to Dr. Gupta.

"Since other types of bacterial infections have been reported in the prostate, and the prostate contains lymphoid cells, that organ may be a source of seminal HIV," Dr. Gupta said. "Thus, a fluctuation of viral replication from infected cells present in the prostate would be the cause of intermittent shedding."

University of Pittsburgh investigators are following up by performing genetic analysis of HIV from the prostate, testis, semen and blood to more directly determine the origin of seminal virus.

This study was a collaboration between the department of infectious diseases and microbiology at the Graduate School of Public Health, and the department of molecular genetics and biochemistry and the department of pathology in the School of Medicine, both at the University of Pittsburgh; and the department of gynecology and obstetrics at Northwestern University Medical School. The study was supported by grants from the Public Health Service and by the Pathology Education and Research Foundation of the University of Pittsburgh.

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