Regular Antiretroviral Therapy Reduces HIV in the Female Reproductive Tract

Globally, 35 million people are living with HIV and 2.1 million are newly infected each year. Vaginal transmission accounts for the majority of new HIV infections worldwide. A recent HIV prevention clinical trial demonstrated 93% protection against secondary heterosexual transmission when infected partners received early antiretroviral therapy (ART), medications that treat HIV.

For the first time, investigators in the Division of Infectious Diseases at the University of North Carolina School of Medicine have determined how antiretroviral therapy (ART) affects the way HIV disseminates and establishes infection in the female reproductive tract. These observations have significant implications for future HIV prevention, vaccine and cure studies.

‘For the first time, investigators have determined how antiretroviral therapy (ART) affects the way HIV disseminates and establishes infection in the female reproductive tract. These observations have significant implications for future HIV prevention, vaccine and cure studies.’

The findings were published in the Journal of Clinical Investigation.

J. Victor Garcia, study co-author, and a professor of medicine in the Center for AIDS Research, the Institute for Global Health & Infectious Diseases, and the Division of Infectious Diseases at UNC, said, "Surprisingly, it does not matter how a woman is exposed to HIV - vaginally, rectally, etc. - the virus goes very quickly to the female reproductive tract. Your body's CD4 T cells, which are the cells HIV infects, also migrate to the female reproductive tract shortly after exposure. It is like putting more kindling on a smoldering fire."

Using humanized mouse models, Garcia and his team also noticed that CD8 T cells, the cells in the body that fight infection, are delayed in getting to the female reproductive tract. This delay allows HIV to establish itself not only in the female reproductive tract, but also in cervicovaginal secretions.

Garcia said, "Your CD8 T cells, which are supposed to protect you, are not arriving in the female reproductive tract in time. When we think about potential vaccines against HIV, this is important information to have."

Yet, when ART is taken regularly, the likelihood of transmission rapidly declines.

Angela Wahl, study co-author and an assistant professor of medicine in the Division of Infectious Diseases at UNC School of Medicine, said, "Once ART was introduced into our models, the number of infected cells in the female reproductive tract and cervicovaginal secretions vastly decreased. However, even on therapy, there is still residual virus in the female reproductive tract, just not enough to transmit infection. And these remaining infected cells are persistently making HIV RNA. This has implications for cure research and indicates that the female reproductive tract could represent a potential reservoir for HIV during therapy."

Source: Eurekalert