Stopping Sexual Transmission of HIV
By Rowena Johnston, Ph.D., and Jeffrey Laurence, M.D.
May 15, 2008—The ease with which HIV is sexually transmitted is influenced by a number of factors, including the presence of other sexually transmitted infections, especially those that cause internal or external genital ulcers. amfAR grantee Eva Rakasz, Ph.D., of the Primate Research Center in Madison, Wisconsin, writing in the April issue of Journal of Virology, explored how SIV—the monkey AIDS virus—infects female macaques. Her research raises questions regarding the best ways to approach designing new HIV prevention technologies.
Such research is critical at this juncture in the AIDS epidemic. Scientists know that people have up to a threefold greater risk of acquiring HIV sexually if they are infected with herpes simplex virus HSV-2, a common cause of genital ulcers. This observation led doctors to suspect that herpes-suppressive medication might reduce the risk of HIV transmission. But a controlled trial conducted among thousands of men and women in various sites around the world failed to show an impact of HSV treatment with acyclovir on new HIV infections.
In the study, genital ulcerative disease was reduced by over one-third in those receiving acyclovir, but without cutting the rates of HIV infections. It is possible that this level of reduction was insufficient, but it is also necessary to know much more about the mechanisms whereby HIV is transmitted sexually. Scientists have determined that genital inflammation in HIV-positive men leads to accumulation of thousands of HIV-infected cells in their semen, which may target cells in the female reproductive system. What is unclear, however, is whether, or how, other mechanisms operate to increase the risk of acquiring HIV when herpes or other sexually transmitted infections are present.
Rakasz and colleagues sought to understand some of those mechanisms by pinpointing the sites of viral entry and viral growth in female monkeys whose vaginal and cervical tissues were treated to mimic genital herpes ulcers. Among these monkeys, transmission of SIV via infected cells was four times more common in sites of visible genital ulcerative disease. But most surprising was the speed with which the virus was subsequently able to enter the immune system via the lymph nodes of these animals. Within 24 hours, virus was found in lymph nodes in the vicinity of the vagina, and after two days, virus had already spread throughout the body, as evidenced by its presence in lymph nodes located under the animals’ arms.
So where does this leave us? Rakasz suggests that the speed of virus dissemination throughout the body—“more akin to intravenous injection,” she warns—will make development of an AIDS vaccine all the more daunting since vaccines generally take many days, if not several weeks, to facilitate the clearing of an infection. More work on other prevention technologies such as microbicides, together with behavioral interventions that can be widely and easily implemented, remain key to preventing the spread of HIV.
Dr. Johnston is amfAR’s vice president of research. Dr. Laurence is amfAR’s senior scientific consultant.