HAART won’t completely eradicate HIV in semen

Study adds weight to safe sex’ emphasis

AIDS researchers have been sounding the alarm for several months now because new studies show that if men on highly active antire tro viral therapy (HAART) have sex without condoms, they could be spreading antiretroviral-resistant HIV to their partners.

While clinicians have emphasized the safe-sex message since HAART first became available, they now have clinical data to back up their claim that HAART does not completely eradicate HIV in semen. And worse, it may be possible for men to spread HIV that has mutated and become resistant to the triple-drug therapies they are taking. Much of the same research is helping scientists and physicians gain a better understanding of how HIV is transmitted through genital secretions, and how sexually transmitted diseases enable HIV to spread more easily.

"Men are the main transmission route of the disease, and it has to be that genital secretions are the route to understanding transmission of the disease," says Myron S. Cohen, MD, professor of medicine, microbiology, and immu no logy and chief of the infectious disease division at the University of North Carolina at Chapel Hill.

"Since 1990, we’ve tried systematic studies to understand the biology of HIV transmission in male genital secretions," Cohen says.

The work he and other researchers have undertaken is examining how much HIV is in semen and how this amount corresponds to the amount of HIV in the bloodstream.

They also have studied how these levels of virus change when men have other sexually transmitted diseases, such as gonorrhea or syphilis. Another study, published in AIDS, evaluated HIV-infected men’s blood and genital secretions for HIV-1 resistance to antiretroviral agents.1

The research has taken some interesting turns. For example, Cohen says, investigators wanted to discover whether men with STDs were at greater risk for spreading HIV because the STDs somehow increased the effectiveness of HIV transmission. They conducted a biological study of the semen of HIV-infected men in Africa who also had gonorrhea. They found that men whose gonorrhea had led to urethritis, a condition in which the penis excretes pus, had 10 times more HIV in their semen than men without urethritis.

"Once we treated urethritis, [the amount of HIV] was reduced," Cohen says. "So urethritis drastically increases the amount of HIV that the partner would be exposed to."

STD may cause faster replication

Investigators found that the local inflammation caused by the urethritis either allowed the HIV to replicate faster or allowed more HIV to escape from the blood, he adds. So far, their ongoing research indicates that the inflammation allows the virus to replicate faster, but the final answer is uncertain.

A second body of studies focused on the effects of antiretroviral drugs. "If you live in the United States and take antiretroviral drugs, you reduce the virus in the bloodstream, so how much do you reduce the virus in semen, and how often does the virus become resistant while you’re taking therapy?" he asks.

For example, picture an HIV-infected man on HAART. Over time, the man’s virus becomes resistant to his therapy. Will the man transmit this HAART-resistant virus to the next person he has sex with? If so, the drugs the HIV-infected man took in his HAART regimen will be useless to his newly infected partner.

"We’re used to seeing drugs as beneficial to the individual, but we must also consider the community effects," Cohen says.

The AIDS study published by Cohen and other researchers late last year showed that HIV drug therapies could lead to widespread HIV resistance patterns in much the same way that antibiotic use has led to a high prevalence of antibiotic-resistant bacteria.

"If we’re not careful that these drugs are enough to kill all the virus, then we’ll lose the effects of the drugs on the next generation," Cohen cautions. "The point is, it’s not stupid to worry about the public-health ramifications of these drugs."

The study, which was written by Cohen, Joseph J. Eron, MD, associate professor of medicine at the University of North Carolina in Chapel Hill, and other researchers, concluded that HIV-1 variants with genotypic resistance markers are present in the male genital tract. These variants evolve over time when the men are on incompletely suppressive antiretroviral therapy.

The study also found that reverse transcriptase genotypic resistance markers were present in seminal plasma at baseline in three out of six individuals with previous experience with reverse transcriptase inhibitors. Eight out of 10 men had new resistance mutations in their blood or seminal plasma or both.

When antiretroviral agents penetrate the genital tract poorly, they may allow ongoing replication in this compartment even when there is an apparent effectiveness of the therapy in the systemic compartment.

If these resistant variants are sexually transmitted, there may be a negative impact on treatment outcomes in newly infected individuals and on the spread of the disease within a population. Public health officials should make it a top priority to focus on therapeutic strategies that fully suppress HIV-1 in the genital tract, the study concludes.

The study concurs with other research indicating that HIV-1 in the male genital tract is in a biologically separate compartment, and the virus is at least partly produced locally and may be under different selective pressures from the virus in the systemic compartment.

Some men appear to be hypersecretors of HIV RNA in seminal plasma, and they may be particularly prone to incomplete suppression of HIV replication in the genital tract and therefore at greater risk of shedding resistant HIV-1.

Reference

    1. Eron JJ, Vernazza PL, Johnston DM, et al. Resistance of HIV-1 to antiretroviral agents in blood and seminal plasma: Implications for transmission. AIDS 1998; 12:F181-F189.