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Before Susan Allen’s research, scientists believed that most spouses would share the same HIV status. But her work with couples in Africa showed that 14% of women tested were in an HIV “discordant” relationship, where one partner is positive and the other negative. Allen’s research group, the longest-standing and largest heterosexual HIV-discordant couples’ cohort in the world, is developing prevention strategies tailor-made for couples in Rwanda and Zambia.
  A Belgian physician, Nathan Clumeck, passing through the city in 1984 sent young pathology resident Susan Allen on what would become the long, strange trip of her life.
     In San Francisco, Allen was spending long days conducting autopsies on young gay men who had wasted away and died of a combination of unusual diseases. When Clumeck visited, he told baffling stories of his own. Young Africans in his infectious disease clinic in Brussels were dying of typically curable tropical diseases.
     “This sounded so much like what we were seeing in San Francisco—young, healthy people dying at a 100% rate of diseases that shouldn’t have been lethal,” says Allen, a professor at the Rollins School of Public Health (RSPH) since 2004 and a member of Emory’s Center for AIDS Research. “The only difference was that the Africans were heterosexual, both men and women, and presenting with different diseases.” Indeed the diseases affecting Clumeck’s patients and the emerging epidemic in the United States turned out to have the same cause, HIV, which led inevitably to AIDS.
     In record time, Allen hammered out 150 applications to foundations to explore what was thought to be an emerging tropical disease. She received funding for four along with money from the state of California, which was spending more money on AIDS than the federal government at the time. The grants were Allen’s ticket back to the developing world where she was born and raised.
     The timing and circumstances fit: She spoke fluent French, she had a diploma from the Liverpool School of Tropical Medicine in England, and Rwanda had no pathology labs or pathologists. Allen offered to set up a laboratory and run it, and the Rwandans accepted, marking the birth of Projet San Francisco in 1986.
     Over the past 15 years, that program has evolved into the Rwanda Zambia HIV Research Group (RZHRG), one of the most successful and prolific in Africa. Founded and directed by Allen, it now has headquarters at the RSPH and continues to grow in size and scope. Along with colleagues on the ground in Africa, Allen employs 15 public health student interns who analyze data and work on the front lines in Rwanda and Zambia. Her husband, Eric Hunter, also works on the AIDS front and is professor of pathology and laboratory medicine in the Emory School of Medicine and a Georgia Research Alliance Eminent Scholar.
  Point of contact  
  Just a year after a test for HIV became available, Allen established a mobile HIV testing site in 1986 in Kigali, Rwanda, the first of its kind on the African continent.
     Initially, researchers tested nearly 4,000 pregnant women visiting prenatal care clinics. “Women getting prenatal care are a convenient sample because they are usually healthy people who represent the general population, and they willingly seek care,” says Allen. “Unlike most of the people you see in the medical system, they are not sick.” In the first year of screening for malaria and HIV, the researchers found an alarming 29% of the women had positive antibody test results for AIDS.
     “We were stunned,” Allen says. “We had no idea.”
     At first, Allen and her coworkers hoped HIV would be similar to hepatitis B. “This test detects antibodies, an immune response to infection,” she says. “And most people who get viral infections such as hepatitis B get over it and clear the infection. Although they don’t have virus anymore, they do have antibodies in their blood.”
     However, back in the United States, the epidemiology showed a darker development. HIV could lie dormant for many years before a person got sick, and the eventual outcome was death.
     In the shadow of emerging scientific facts, developing culturally appropriate counseling messages for Rwandan women was a large challenge. Adapting counseling messages from those developed in California, Allen’s group taught the women to use condoms to avoid infection if they were HIV negative or to avoid infecting their husbands if they were HIV positive. Although condoms were a popular contraceptive in Asia, they were almost unknown in Africa at the time.
     Allen realized that her Rwandan cohort could help develop prevention strategies tailor-made for Africa. Testing in Kigali had identified 1,458 HIV-positive and HIV-negative women, a large group of study participants who could help the researchers trace the natural history of HIV over time and devise a way to reduce risk of transmission.
  The couples approach  
  By 1988, the women who participated in the testing consistently were asking that their spouses be tested as well. Most of the men were more than willing, and these tests revealed yet another surprise for AIDS researchers worldwide: 14% of the women tested were in an HIV “discordant” relationship, where one partner is positive and the other negative.
     “These results were big news,” Allen says. “Before this study, scientists believed spouses would share the same HIV status.”
     The RZHRG now follows the longest-standing and largest heterosexual HIV-discordant couples’ cohort in the world. Once the group began testing both husbands and wives, it became evident that both partners needed to know the other’s HIV status to protect themselves from HIV.

     Counseling tailored specifically to the status of each individual couple (both HIV negative, both HIV positive, or HIV discordant) became the foundation of the couples’ voluntary counseling and testing (CVCT) method, which has proved successful in Rwanda.
     The Zambia–Emory HIV Research Project (ZEHRP) in Lusaka maintains the world’s second largest cohort. Like the Rwandan model on which it is based, the site in Zambia promotes CVCT as a method of HIV prevention and as an entry-point into HIV clinical care, including prevention of mother-to-child transmission and antiretroviral therapy programs. ZEHRP has three satellite clinics in the surrounding districts of the capital city and one mobile clinic in addition to the main site.
     In 2004, a third CVCT research site was opened in the northern Copperbelt region of Zambia. Although smaller than its two sister sites, Ubumi Bwesu-ZEHRP is an integral part of the research.
  Involving husbands  
  The refinement of testing and counseling techniques is still a work in progress, but it has come a long way since voluntary testing and counseling began in the United States. In adapting counseling messages for use in Rwanda, researchers told the women the virus was transmitted sexually and through contact with blood. They advised those tested to use condoms and to refrain from conducting traditional scarification without sterilized razors.
     Almost immediately, the women raised a red flag. “They told us our condom demonstration was great but that they couldn’t just go home and tell their husbands to use them,” Allen says. They asked if they could bring their husbands in to talk with the counselors.
     When husbands were invited to join the study, approximately one-third came in for free test results without additional incentives such as money or transportation. In the process, researchers discovered the existence of HIV-discordant married couples.
     That finding led to another set of questions: Did the results indicate that the person with the positive test was infected a long time ago and was no longer highly contagious when he or she met this spouse? Or was the virus less easily transmitted than researchers originally thought? And what were the best ways to ensure the healthiest outcomes for both partners and their children? The discordant-couples studies aimed to answer these questions about heterosexual transmission of HIV.
      Because the researchers wanted to trace what happens during transmission, they chose to focus on discordant couples. From 1992 onward, the group required couples to be tested together and to sign a joint consent form agreeing to be in the room together when the results were disclosed and to discuss them as a couple.
  The impact of genocide  
  In the Rwandan genocide of 1994, Allen’s original study cohort—along with the ethnic Tutsis, the economy, the political system, and, indeed, the fabric of the country—was nearly destroyed. All the members of Allen’s group who were able fled. Most of the rest died.
     “When the Rwandan president’s plane was shot down, I was actually in Zambia trying to help them get HIV testing up and running there,” says Allen. “I was pregnant and I had left my 13-month-old son behind in Kigali. When everything hit the fan, I tried to get back, but no one would fly into Kigali. I sweated it out for five or six days until I found out my son was alive and had gotten out with an overland convoy with his dad and others who had been staying in our house. It was very scary.”

     Allen waited a few weeks to see if the situation would calm down and to find out what was happening to the rest of their staff. “When it became apparent things weren’t calming down anytime soon, we had two choices,” she says, “to terminate and give the rest of the grant money back or try to find a new place to work. Since I had just come back from Zambia and met the AIDS community down there, I flew back and approached the ministry of health and said we’d like to relocate our research base. They were very supportive.”
     When the genocide ended, Allen returned to Rwanda to put something back together. Half the staff had been killed, and the study participants were scattered. It took several years to find out what happened to many of these people and to convince funding agencies that Rwanda was stable enough for research. From 1994 to August 2001, the project operated on a shoestring. Then in 2001, Allen’s group received a grant from the World AIDS Foundation followed by NIH grants in 2002. The International AIDS Vaccine Initiative became interested in building up the discordant-couples cohorts again.
     “Now we’re bigger than we were when the genocide began,” says Allen. “We’ve got about 1,000 discordant couples enrolled in Rwanda, a vaccine laboratory has been built, and we’ve recently started our first HIV vaccine trial. Interestingly, one piece of the vaccine was derived from the virus of a Rwandan man in one of our studies in 1992. We can tell the president and people of Rwanda that their participation in HIV research 13 years ago has brought us to the point where there’s a vaccine product.”
     Also, either because of population shifts after the genocide or education and behavior change, HIV prevalence among pregnant women in Kigali has dropped to 15% from 29% in 1986.
  Finding a way
During three years in the Peace Corps in Benin, Joe Barker saw the devastation of the AIDS epidemic firsthand. He knew he wanted to help, and he found a way through an internship with the Rwanda-Zambia HIV Research Group (RZHRG).
     “Working for RZHRG has given me a sense of the importance of effective research and how it directly affects, creates, and sustains program interventions,” says Barker, an MPH student who spent the summer of 2005 at Projet San Francisco, RZHRG’s site in Kigali, Rwanda. His field study, supported by the Anne E. and William A. Foege Global Health Fund, taught Barker the nitty-gritty of managing clinical trials, from coordinating budgets and personnel to administering grants. He also learned about the basic science of HIV transmission among African couples, and he conducted primary research on their comprehension of and motivation to participate in clinical trials, which will be the basis of his thesis.
     “I now understand that collecting good data in developing countries is no small feat,” says Barker.
     He is co-author of two manuscripts with Susan Allen that use a cohort that he and another student defined. They gathered demographic information about couples enrolling in studies in Kigali and Lusaka, Zambia, examining the effects of alcohol use on condom use among male partners in HIV-discordant couples.
     Barker says RZHRG is a prime example of local empowerment and culturally appropriate public health interventions. “It is certainly not a primarily American or European project. Many of the senior staff and all the lab technicians, nurses, counselors, and administrative staff are either Rwandan or Zambian,” he says. “Dr. Allen emphasizes the importance of training and collaborating with local experts and scientists. Witnessing a non-ethnocentric approach toward the HIV epidemic was one of the most important lessons I gained.”
    After graduation, Barker hopes to spend two years in Kigali coordinating a phase III randomized control trial studying HIV/HSV-2 transmission. He says he feels incredibly lucky. “I was looking for a truly international, grass roots organization doing powerful public health work, and I found it.”


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