WASHINGTON, D.C., January 22, 1997 — Researchers have focused extensively on controlling HIV-1 RNA levels in the blood of HIV-infected individuals to treat AIDS. But to stem the major route of transmission and overall spread of AIDS, they must look at the activity of HIV in the semen. Researchers from the University of Pittsburgh have detected free HIV-1 RNA, or viral load, at levels 10 to 1000 times greater in all stages of disease than previously measured in the semen of HIV-infected men.
"This study substantiates concern that a man can transmit HIV at any time after his initial infection," cautioned Phalguni Gupta, Ph.D., associate professor of infectious diseases and microbiology at the University of Pittsburgh Graduate School of Public Health, who will present these findings at 10:30 a.m. (EST) on Saturday, Jan. 25, at the Fourth Annual Conference on Retroviruses and Opportunistic Infections in Washington, D.C.
Using the NASBA (Nucleic Acid Sequence Based Amplification, Organon Teknika) method, researchers quantified the HIV-1 RNA in semen and blood samples from 34 homosexual men at varying stages of the disease. They found that viral load in both blood and semen accurately monitors viral activity. In this first report to monitor semen viral load over an extended period of time, researchers found that semen viral load increases with progression of the disease in the majority of patients.
"We believe that a unique strain of virus could have arisen in the semen but not in the blood," Dr. Gupta commented. Attributing the evolution of the virus in the semen to biological differences in the seminal and blood environments, Dr. Gupta said that "to prevent transmission of the virus through the primary mode of transmission -- sexual contact -- we need to devise a vaccine against the strain of virus that is present in the semen."
This study also is the first to show that using antiviral therapy reduces viral load in semen. Administering a combination therapy consisting of a nonnucleoside reverse transcriptase inhibitor and a protease inhibitor diminishes the viral load below detectable levels in both semen and blood in a total of six patients examined. Nonnucleoside reverse transcriptase inhibitors interfere with the replication of the virus, while protease inhibitors block the process of packaging viral genetic messages.
"We have determined in previous studies that reduction of viral load in blood plasma improves patient prognosis," said John W. Mellors, M.D., associate professor of medicine at the University of Pittsburgh Medical Center (UPMC). "It has been difficult to quantify viral activity in other organs and tissues, which has prohibited an accurate portrayal of overall viral load in the body and the response to therapy." Accurate detection of viral load in the semen, "offers researchers one more tool to analyze disease activity in other tissues and helps to gauge the effectiveness of new therapies," according to Dr. Mellors.
Other Pitt investigators involved in the study are: Charles Rinaldo, Ph.D., professor of pathology and microbiology and director of the Pitt Men's Study; Lawrence A. Kingsley, Dr.P.H., associate professor of epidemiology and microbiology; Sharon Riddler, M.D., assistant professor; and Mandaleshwar Singh, Ph.D., research assistant professor. Researchers from Organon Teknika include Susanna Schreiber, Ph.D., and Michael Cronin, M.S.
The Pitt Men's Study is one of four centers participating in the National Institute of Allergy and Infectious Diseases Multi-center AIDS Cohort Study, a long-term research project focused on HIV-infected men.
HIV/AIDS researchers at the UPMC have pioneered the use of viral load testing in HIV-infected patients, triple-drug therapy to reduce disease activity and topical agents to prevent sexual transmission of HIV in women. UPMC investigators also are conducting research on AIDS-related malignancies and dementia, AIDS vaccines and AIDS prevention strategies.