Research confirms HIV virus still may be transmitted after HAART
Research confirms HIV virus still may be transmitted after HAART
Public health efforts must focus on safe-sex practices
While highly active antiretroviral therapy (HAART) has been reducing HIV to undetectable levels in patients for some time now, clinicians have always said the fight to prevent HIV infection must continue unchecked. A study published in the Dec. 17 issue of The New England Journal of Medicine has now confirmed that assertion. The study concludes that HIV-infected men on HAART still may harbor the virus in seminal cells, even if they have no detectable levels of viral RNA in plasma.1
"If you pass these cells to uninfected men or women, these cells could potentially produce virus and infect those people," says Roger J. Pomerantz, MD, professor of medicine, biochemistry, and molecular pharmacology, chief of the division of infectious diseases, and director of the center for human virology at Thomas Jefferson University in Philadelphia. Pomerantz was one of seven co-authors of the study.
"The risk is probably very low, but it’s not nonexistent," Pomerantz says. "So the fact that these cells can still be grown in vitro suggests these people should still have safe-sex practices and consider themselves not cured of the disease."
The study suggests that people who adhere to their anti retro viral regimen may have residual virus that can transmit, says Kenneth Mayer, MD, chief of the infectious disease division of Memorial Hospital in Pawtucket, RI, and professor of medicine at Brown University in Providence, RI.
While getting people into treatment might help decrease transmission on a population basis, it does not mean individuals should behave as though they are no longer infected, Mayer says.
"For that individual person, just because your sexual partner is taking triple therapy and it’s undetectable in the blood, it doesn’t mean your partner might not be infectious at any given point in time," he explains.
Earlier research has shown that HIV infectiousness is highly variable between individuals and even within a particular person. A person may have positive viral semen cultures at one point in time and negative cultures a few months later, Mayer notes. Thus, the Thomas Jefferson University study underscores the importance of teaching HIV-positive people to prevent transmission for the rest of their lives, he says.
"We always stress that patients, regardless of their viral load, should be viewed as infectious," says Aaron E. Glatt, MD, chief of the division of infectious diseases at Catholic Medical Centers of Brooklyn and Queens and professor of clinical medicine at Albert Einstein College of Medicine in the Bronx, NY.
"I try not to say you have a negative or zero viral load," Glatt adds. "I stress to patients that we are not able to detect virus because the tests we use are at fault and can’t detect low levels."
The research implies important policy messages that should be reinforced continually, especially to young people, says Cliff Morrison, ACRN, FAAN, director of staff development for Telecare Corp., a behavioral health company in Oakland, CA. Morrison is the former deputy director of the AIDS Health Service Program in the Institute for Health Policy Studies in San Francisco.
"I think after almost 20 years of looking at prevention policy relating to the epidemic, it’s obvious that any time there’s new information, we have to get it out there quickly," Morrison says.
Researchers in the Thomas Jefferson University study collected peripheral blood and semen samples from seven men with HIV-1 infection. The men were identified from more than 400 men with HIV-1 infection who were treated in the university’s clinics. The seven had received HAART for five to 41 months, and they had no detectable RNA in plasma. They had plasma levels of HIV-1 RNA below 400 copies per milliliter when measured by a reverse transcriptase polymerase chain reaction assay on three occasions at least one month apart. When blood and semen samples were obtained for the study, their plasma HIV-1 RNA levels were below 50 copies per milliliter.
Researchers isolated cells and analyzed the samples using a quantitative polymerase-chain-reaction assay, looking for proviral DNA, Pomerantz says. They then cultured the cells with uninfected blood cells from an uninfected individual and stimulated the cells to see if the virus would replicate, he explains.
The study’s findings included the following:
• HAART inhibited viral replication in the bloodstream and in the genital tract, although cell-associated viral DNA was detected in peripheral-blood mononuclear cells from all the men.
• Cell-associated proviral DNA was detected in the seminal cells of four men, with the number of copies of HIV-1 DNA ranging from fewer than five to 90 per million seminal cells.
• Researchers recovered replication-competent HIV-1 from peripheral-blood lymphocytes from three men and from seminal cells from two of the three.
• The virus isolated from seminal cells of two men is potentially capable of initiating a primary infection in a sexual partner even though the men were receiving HAART and had undetectable levels of viral RNA in plasma.
The findings suggest that at least two of the men were still infectious, Pomerantz says.
Researchers also examined whether the men’s virus showed any resistance mutations to the protease inhibitors, and they found no real resistance. This means the medication successfully suppressed the virus, although it did not totally eradicate it.
"These viral strains are fossil or archival viruses that were there lying fallow for many years, probably from the time after infection," Pomerantz says.
Clinicians should use studies like this to emphasize to HIV patients that safe sex still should be the norm, Mayer says. "Having a partner treated for HIV is not a chemical condom," he says.
Reference
1. Zhang H, Dornadula G, Beumont M, et al. Human immunodeficiency virus type 1 in the semen of men receiving highly active antiretroviral therapy. N Engl J Med 1998; 339:1,803-1,848.
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