Aug. 30, 2000 Antiretroviral therapy for HIV patients can be a double-edged sword, according to University of Pittsburgh AIDS researchers and their Brazilian colleagues. Investigators showed that while the drugs can greatly reduce the amount of infectious HIV in semen (viral load), a substantial percentage of men may still be able to transmit the virus sexually. This is the first-ever study to simulate a clinical environment in looking at the effects of antiretroviral drugs on HIV concentration in semen.
The findings, made by researchers at the University of Pittsburgh Graduate School of Public Health (GSPH) and School of Medicine, and the Universidade Federal do Rio de Janeiro (Brazil), are published in the August 15 issue of the Annals of Internal Medicine.
"Our study is the first to show that, in a real-world setting, a substantial percentage of HIV-positive men have active, potentially infectious virus in their semen, even after six months of therapy," said Lee Harrison, M.D., associate professor of medicine and epidemiology, director of the Public Health Infections Diseases Lab at the University of Pittsburgh and senior author of the study.
Previous small, short-term studies have suggested that antiretroviral therapy reduces, but not completely eliminates, seminal viral load in HIV-infected men. But, because these earlier studies were not definitive for a number of reasons, scientists remained unsure whether the findings would translate into a larger community setting. The Pittsburgh-Rio de Janeiro study provides a clearer picture of just how resilient -- and potentially transmittable -- the AIDS virus is during therapy.
"Certainly, current drug regimens have been shown to reduce the likelihood of sexual transmission of HIV, and our study has provided additional evidence that these regimens are effective in reducing viral load in both the blood and semen of many men in our study," commented Paulo Barroso, M.D., Ph.D., assistant professor and head, Infectious Diseases Service, School of Medicine, Universidade Federal do Rio de Janeiro. "Nonetheless, a significant proportion of men who underwent therapy and subsequently felt well remained potentially infectious and therefore continue to pose a public health risk unless they monitor their sexual behavior carefully."
The study was conducted at the Hospital Universitário Clementino Fraga Filho in Rio de Janeiro from November 1996 through May 1998. Ninety-three HIV-infected male volunteers agreed to undergo antiretroviral therapy, with the decision to start, change or stop therapy left up to the volunteers and their personal physicians, thus simulating a clinical environment. All but two of the subjects were antiretroviral-naïve (had never been on antiretroviral therapy).
Eighty of the study subjects began with a double nucleoside reverse transcriptase inhibitor (NRTI) drug regimen. The best known NRTI is zidovudine (Retrovir), formerly known as AZT. NRTIs prevent the integration of HIV genes into the host cell's genome. Another type of drug, known as a protease inhibitor, was added to the regimen for 13 of the subjects. Protease inhibitors block the release of mature, infectious HIV particles from HIV-infected immune cells. By the end of the study, 19 subjects were using the triple-drug program, having changed drug regimens upon the advice of their own physicians.
After six months of therapy, there was a 66 percent reduction in the number of study subjects with detectable seminal HIV viral load. Of the 64 subjects who had detectable HIV in their semen before initiating therapy, 44 had undetectable levels after six months. Also, those volunteers who used the double nucleoside had a statistically significant reduction in seminal HIV viral load as measured at all follow-up visits one, two, three and six months after initiation of therapy.
"In spite of these impressive treatment outcomes, a third of the treated men had infectious virus in their semen after six months, including 13 percent of patients who were taking a protease-inhibitor-containing triple-drug regimen" said Dr. Barroso. "Thus, because there is no guarantee that HIV-infected individuals will not be infectious themselves, they should continue to practice safe sex and follow medication instructions to the letter."
In a landmark study conducted previously at the University of Pittsburgh's GSPH, investigators found infectious HIV in the semen of a small group of men who had received antiretroviral therapy and who were in various stages of disease. More recent work has shown that, even after HIV-infected patients underwent antiretroviral therapy, so-called HIV "provirus" remained integrated within the genome of cells in semen. Whether these patients are infectious or not, however, is not known.
"In general, it's safe to say that men who have a detectable viral load after six months on therapy have a high likelihood of carrying - and possibly sexually transmitting - infectious HIV," said Dr. Harrison. "We suspect that the seminal HIV in these men is drug resistant, although definitive studies examining this issue are still ongoing."
A further concern, according to Drs. Harrison and Barroso, is that treated men do not become complacent because they are on aggressive therapy. This study confirms the finding that infectious HIV may still lurk within their semen.
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