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Published On Nov 28, 2014

Clinical Research

New Allies in the HIV Fight

An MGH program in South Africa partners with young women to research the earliest phase of HIV infection.

Nomcebo Msomi is a 22-year-old South African woman with a shy smile. She lives in Umlazi, a township in the province of KwaZulu-Natal. Twice a week, she visits a storefront clinic in a local shopping mall to get tested for HIV.

The KwaZulu-Natal province has the heaviest burden of HIV in the world. Roughly one-third of young pregnant women test positive for the virus. This grim epicenter of infection has recently given rise to a fascinating new project —Females Rising through Education, Support and Health (FRESH). The program is both a research study and community outreach program, an attempt to synthesize science and social good.

It began with a knotty research problem. The events that occur at the earliest stages of HIV infection — and how the immune system reacts to them — have often proven challenging to study. There is a very small window of opportunity to study the body’s immune responses, and the virus itself, during the earliest stages of infection before antibodies develop. That window is known as the acute infection phase. Because of its brevity, researchers worldwide have found it difficult to recruit individuals who can provide samples during this acute phase.

With the FRESH program, scientists from the Ragon Institute of MGH, MIT and Harvard have devised a novel study that overcomes this barrier. They recruited Nomcebo and hundreds of other young, healthy HIV-negative women from high-risk communities. These volunteers have agreed to make frequent visits to a clinic to provide samples and check for any signs of acute HIV infection.

As a draw for the young women to join and keep participating, FRESH includes a comprehensive program of personal enrichment. It meets twice a week, on the same day the participants come for their HIV screening. The curriculum includes job training and interview skills, as well as information about women’s health, HIV, sexually transmitted infections and family planning.

All FRESH participants are at high risk of contracting HIV, and close monitoring enables researchers to pick up infection as soon as it becomes detectable in the blood, which occurs within about 10 days of exposure. The ability to sample blood and vaginal cells at this moment of “acute infection” provides a rare opportunity.

“The whole game is won or lost in the first handful of days,” says Dr. Krista Dong, an infectious disease specialist from the Ragon who leads FRESH. “This is why we designed a program that follows the women so closely.”

FRESH sends these specimens to researchers at Ragon Institute affiliated labs in Durban and Cambridge, Mass. There scientists look for clues to help them understand how the immune system recognizes HIV and reacts upon the virus’ entering the body.

Within the first few months following infection, the immune system is able to lower the amount of HIV in the blood until the virus levels off at its so-called set point. This level, which varies widely from person to person, predicts how rapidly the virus will damage the immune system and how rapidly one progresses to AIDS or requires antiretroviral therapy.

“Understanding exactly how the immune system manages the virus is an important step to help develop effective vaccines against the virus,” says Thumbi Ndung’u, who heads the lab in Durban that is studying the FRESH samples. “With this understanding we will be better equipped to develop a vaccine or even find a cure.”

Of the 487 women who have enrolled in FRESH, 15 have tested positive for HIV, as of December 1. In each case researchers detected the virus within days of the person’s becoming infected. The women continue to attend twice-weekly classes and contribute blood and mucosal cells.

Because the program collects samples both pre- and post-infection, scientists are able to study how the HIV activates the immune system in both the blood and the primary site of infection, which is the genital tract. Scientists compare the immune response between women whose bodies respond more or less effectively to HIV to determine what enables them control the virus. Scientists also investigate correlates of infection, such as use of hormonal birth control and the presence of sexually transmitted diseases.

One goal of the study is to identify participants who develop “broadly neutralizing antibodies,” (bNAbs) which are proteins made by immune cells that can inhibit multiple different strains of HIV before cell entry. One of the main challenges of developing a vaccine against HIV is that it mutates so rapidly that even a single infected person will carry multiple versions of the virus.

Researchers hope to harness the properties of BNAbs, which help to hold the virus in check. According to scientists, BNAbs also may reduce the size of HIV reservoirs which are pools of virus that lie dormant and are able to evade both the immune system and antiretroviral (ARV) drugs. 

Last July, FRESH began offering ARV treatment to participants during acute infection. Though policymakers have to yet to recommend treatment at this early stage, evidence suggests that early treatment, like BNAbs, may reduce the size of the reservoir and, possibly, bring eradication of the virus or a cure within reach.

“No one else in the world is treating HIV this early, which is exciting if it proves to be clinically beneficial,” says Dong. “Early treatment also positions FRESH to be a leader in eradication research.”

The young women who provide this precious research opportunity lead immensely challenging lives. The unemployment rate in townships like Umlazi can top 40%, while nearly a third of students fail to graduate from high school. Young women, are infected with HIV at a much higher rate than men of the same age, and also face an epidemic of sexual violence. South Africa has among the highest rates of rape and sexual assault in the world.

The FRESH curriculum was tactically designed to break this cycle and help participants gain financial independence. The program helps them to write resumes, teaches basic computer skills and prepares them to interview for jobs. They also take trips to local businesses including a visit to the research lab in Durban where their blood is sent.

While scientists puzzle out the early immune reaction to HIV infection, Nomcebo looks forward to graduating from FRESH and securing a job that will allow her to provide for her family. She’ll graduate with more choices and the chance for a better future. “That’s win-win,” says Dong. 

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