TGen-led Study Seeks to Understand Why Some HIV-Positive Men are More Infectious Than Others

A new study led by the Translational Genomics Research Institute (TGen) provides insights into the interplay among bacteria, viruses and the immune system during HIV infection.

Currently, doctors measure HIV-positive men's infectivity - their potential to infect others -- based on their blood viral load. However, some men produce large amounts of virus in their semen despite having low levels in their blood. Researchers call this "compartmentalization," where different levels of the virus can be found in different parts of the body; in this case, in the semen, versus the blood.    

Because of the importance of semen in HIV transmission -- in both homosexual and heterosexual populations -- researchers who conducted the study published today in the journal PLOS Pathogens sought to understand how HIV could be localized, or compartmentalized, in the semen.

Significantly, the study revealed a link between higher levels of HIV and higher levels of both bacteria and cytokines, biochemicals that can be described as the immune system's alarm bells.

"Our study is trying to tackle an important problem in HIV research," says Dr. Lance Price, director of TGen's Center for Microbiomics and Human Health, and one of the study's senior authors. "We found that HIV infection affects the relationship between semen bacteria and immune system, and both are linked to semen HIV levels."
 
These findings could point to new ways to control the spread of HIV, says Price. "Our data suggest that semen bacteria may play a role in localized inflammation and HIV viral load in the semen, which is an important target for reducing HIV transmission."

While HIV can be found in many body fluids (semen, vaginal secretions, blood and breast milk), it is most commonly transmitted via semen in both homosexual and heterosexual sex. Homosexual men were the focus of this study because they continue to be the population most at risk for HIV in North America. The study included 27 homosexual men infected with HIV, and 22 homosexual men who were uninfected.

 The 27 infected individuals were examined before treatment, and at both one-month and six-month intervals following treatment with anti-retroviral therapy (ART). Samples from the 22 uninfected participants in the study served as controls.

"By comparing the semen bacteria in both uninfected and infected men, we found that HIV can cause an imbalance in the semen microbiome," says Dr. Cindy Liu, the study's lead author, a clinical pathology resident at the Johns Hopkins School of Medicine, and an adjunct professor at TGen at the time of the study. "This imbalance can be corrected by HIV treatment. This suggests that there are complex host-microbe interactions in the semen."

"We have taken the first step to show that bacteria, HIV, and immune response in the semen may be connected," says Dr. Rupert Kaul, an immunologist from the University of Toronto, and another senior author of the study. "What we need to better understand next is the precise relationship between these three factors - whether the bacterial imbalance is the trigger or the result of the localized immune response."

The authors of the study, "The Semen Microbiome and Its Relationship with Local Immunology and Viral Load in HIV Infection", are particularly excited about what this research may mean for another important patient population.

"Even though we have focused on men whose semen viral load can be controlled with HIV treatment in this study," says Kaul, "we need to study men who continue to have high HIV levels in their semen despite being on treatment. This will be important to improving how we treat patients and control the spread of HIV."

Source: Translational Genomics Research Institute