How prostitutes in Dakar contributed to our knowledge of HIV
By Martha Henry
Phyllis Kanki had thought the S stood for singe, the French word for monkey, but a call to France revealed that the S stood for Senegal—in particular, sex workers in the capital city of Dakar. And that changed everything.
The year was 1984. AIDS was spreading across the world and the death count was quickly rising. Kanki, after receiving a degree in veterinary medicine, was working towards her doctorate in virology in the lab of Max Essex, a professor at the Harvard School of Public Health. Her work had already produced results. Investigating sick macaques at the New England Regional Primate Research Center, she and Essex had identified a retrovirus similar to HIV. The virus would later be named Simian Immunodeficiency Virus or SIV.
“We had identified AIDS-related retroviruses in monkeys that were kept in a research colony in the U.S.,” remembers Essex. He suggested that Kanki look at blood samples from monkeys living in Africa.
Luckily, Essex had ties to Africa through his research on the hepatitis B virus (HBV) with French colleagues who worked in Senegal, a former French colony. One of those researchers, Francis Barin, had spent time in the Essex Lab at Harvard. Now he was back in France. Essex suggested that Kanki contact him about samples.
Barin sent her a series of samples that were labeled T, B, and S. Kanki assumed that B stood for Burundi, a West African country Barin had worked in. She assumed T stood for temoin, the French word for control. The S samples, she thought, probably stood for singe, the French word for monkey.
She ran the samples. The ones labeled B were clearly HIV-1 from humans. The ones labeled T showed no reactivity, so were likely controls, as assumed. The samples labeled S had a slight reactivity to the HIV-infected proteins, but strong reactivity to the monkey virus proteins. “They looked like monkey serum samples reacting to monkey virus,” remembers Kanki. She stopped by Essex’s office to tell him there was nothing unexpected about the human samples, but the monkey samples were interesting and he should ask Barin about where they came from the next time they talked.
Sometime later, Essex, a man known for his calm demeanor, came running into the lab where Kanki was working. He had just gotten off the phone with Barin. “We were shocked to find out that the S actually stood for Senegal. The samples weren’t from monkeys,” remembers Kanki. “They were from female sex workers infected with a virus that was closer to the monkey virus than to the prototypical AIDS virus.”
Barin called Souleymane Mboup, a young virologist at the University of Dakar who ran the public health laboratory tasked with doing sexually transmitted disease (STD) testing for sex workers. Mboup located the women who had provided the original samples and collected new ones. He wrapped upthe new samples like gifts, packed them in his suitcase, and got on a plane. He was headed for Boston—his first trip to the U.S. “And that’s where this collaboration starts with Max,” said Mboup.
For three weeks, Mboup worked with Kanki and others in the Essex Lab. Kanki, Essex, Mboup and their collaborators had discovered a second type of HIV, what would later become known as HIV-2.
What is HIV-2?
Now that a new virus had been identified, there were two big questions: Who was infected and how did the virus affect the people who were infected? To find answers, a consortium was launched between Harvard, the University of Dakar, and two French universities to conduct research on human viruses and related diseases.
“With the aim of equal partnership,” stressed Mboup, “which was important because this was the time of safari research, where most of the people from Western countries came [to Africa] just to get samples and went back and did everything in their privileged labs.” At the time, Mboup’s own hospital lab was small, with two technicians, a battered microscope, and an unsteady supply of electricity. Mboup wanted to build research capacity in Senegal, which would require training people and building the necessary infrastructure.
A Unique Strategy for Sex Workers
In 1985, Senegal was a poor country, about the size of South Dakota, with a population of 6.5 million people, 95% of whom were Muslim. The first documented case of AIDS was identified in 1986 in a migrant worker infected with HIV-1. Though many African leaders ignored or denied the growing AIDS epidemic, President Abdou Diouf, Senegal’s second president, launched an anti-AIDS campaign.
Unique to Africa, Senegal allows prostitutes over the age of 21 to work as long as they register with a health clinic where they get regular checkups and free condoms. This system, put in place in the 1960s to slow the spread of STDs, doesn’t reach all sex workers, notably missing young girls, men, or those who choose not to register, yet practical acceptance of prostitution helps track and slow the spread of STDs. The blood samples Kanki tested at Harvard came from registered sex workers.
Years of Testing
Once Mboup and the Harvard team knew they were dealing with a new type of HIV, their next step was to examine the people in Dakar who had it. Kanki flew to Africa for the first time.
“We wanted to find out whether this new virus was going to cause disease,” said Kanki. “We found the sex workers and they were all healthy. Then we went to the hospitals. If HIV-2 was in West Africa, you would expect to see AIDS cases. Nothing. This was becoming more and more interesting. We did the prospective study to see if it caused disease or not.”
“Finding another virus that was infecting humans that was doing something different was surprising, but also very interesting,” said Kanki. “One could imagine that if there’s that kind of diversity within this newly described family of pathogens, then maybe you can take advantage of that in thinking about vaccines or drugs.”
In 1985, Senegal was the only place in the world where HIV-2 had been identified. Following the sex workers over time was the best way to discover more about the virus. But money was needed to start a prospective study.
Back in the U.S., Deeda Blair, vice president of the Lasker Foundation, introduced Max Essex to Maurice Tempelsman, a businessman with a deep knowledge of Africa. Essex briefed him on the work in Senegal. On the spot, Tempelsman wrote a check to launch the project. It was the first of Tempelsman’s many contributions to Harvard’s work on HIV/AIDS. When the Harvard AIDS Institute (HAI) was established in 1988, Tempelsman and Blair were chosen to chair HAI’s International Advisory Council.
Later funding for the sex workers’ study would come through U.S. Department of Defense, with Kanki, then a post doc, as Principal Investigator.
Of the 400 women in the first survey, 8% were found to be infected with HIV-2. Eventually most registered sex workers visiting Dakar’s STD clinics were followed, allowing researchers to track disease progression as well as identify new infections.
Unfortunately, shortly after HIV-2 was discovered, HIV-1 moved into Senegal. The prevalence of both viruses made it possible to track and observe clinical differences between the two. At the time, there was no known treatment for AIDS.
The study grew from a few hundred to few thousand women over time, as some left the cohort and others joined. The clinics provided free medical care to the women. In later years, registered sex workers in two other cities, Kaolack and Ziguinchor, also joined the study.
Findings
The study continued year after year, with a shared purpose between sex workers, clinic staff, lab technicians, and researchers. They all wanted to stop the spread of HIV. As the testing continued, the accrued data began to provide results.
“HIV-1 came into that group of women at a high enough rate that we were able to compare those two viruses,” said Kanki. “There was a huge difference in the rate of disease between HIV-1 and HIV-2. By seven years after infection with HIV-1, more than 50% of women would have AIDS; but with HIV-2, it was only about 10%. There was a huge difference in the survival curve. What it showed is that HIV-2 is a virus of long-term survivors.”
“Most people infected with HIV-2 did not get clinical AIDS, and those who did didn’t get it as rapidly,” summarized Essex.
A later finding showed that the risk of transmission of HIV-2 is 5 to 9 times less than HIV-1, which may explain why HIV-2 remains largely limited to West Africa. For mother-to-child transmission through heterosexual sex, the rate of transmission for HIV-2 is 10-fold to 30-fold lower than HIV-1.
Perhaps the most interesting finding was that the women with HIV-2 were less likely to get infected with HIV-1 than the women who were not infected. The protection was almost 50%. “We found that HIV-2 infected women actually did seem to be protected, so the rate of getting HIV-1 was lower than if they were negative,” explained Kanki. “That was exciting to us and led us to believe that HIV-2 would be a good model for thinking about vaccine protection.”
“The first thought was that maybe it’s a classical immunity the way other vaccines work,” said Essex. “Unfortunately, that was shown not to be the case. It wasn’t a homerun in the sense of a clear roadmap of how to make a vaccine against HIV-1. But HIV-2 is still yielding hints about how protection might be generated for a subsequent exposure to HIV-1.”
Legacy
The Senegal sex workers study continued for over 25 years, making it one of the longest HIV natural history studies in the world. During that time, a lot was learned about HIV-2, but there were other important benefits.
The data and samples painstakingly collected from thousands of sex workers have helped the world learn about HIV and are still being used to learn more about infectious diseases in West Africa. The samples were recently used when one of Kanki’s graduate students published a paper about the prevalence of Zika in West Africa between 1992 and 2016.
From the beginning, Souleymane Mboup had wanted to expand research capacity in Senegal. Working with his collaborators, he accomplished that goal.
“Before 1985, there was a tiny bacteriology lab in the hospital with myself and two technicians. Over time, with the various research grants, we were able to expand the lab. Today, there is a state-of-the-art equipped lab with a staff of about 120 people and a very high reputation,” said Mboup.
There was a busy two-way flow of students, lab technicians, and scientists between Harvard and Dakar. Researchers devoted themselves whole-heartedly to the work. Lessons were learned and life-long friendships were formed.
As Max Essex remembers, “I learned a lot in Senegal about the importance of having people in the host country take leadership and also to have the respect of their government and others who can approve and move a project forward.”
In 1996, Essex put those lessons to use when he was the driving force in establishing the Botswana Harvard AIDS Institute Partnership (BHP). At the time, Botswana’s adult HIV prevalence was about 25%. The BHP grew to become one of the top HIV/AIDS research centers in Africa. Ibou Thior, who became the BHP’s first director, was a Senegalese physician who had previously been in charges of the sex worker cohort.
Phyllis Kanki became a professor at Harvard Chan and now has an office down the hall from her old mentor. She was the driving force in establishing AIDS Prevention in Nigeria (APIN) in 2001, a non-profit which began by providing AIDS prevention services and later helped scale up Nigeria’s HIV/AIDS treatment program.
In the last 30 years, Senegal’s population more than doubled to 15 million people. Today, the prevalence of HIV in Senegal is 0.4%, very low compared to most other countries in sub-Saharan Africa. The prevalence of HIV in sex workers is 6.6%, also low when compared to other African countries where rates can run as high as 35%. According to a UNAIDS, there are about 41,000 people living with HIV in Senegal, the majority of whom have access to life-saving antiretroviral therapy.
There is, as always, work to be done. In June 2017, Souleymane Mboup helped launch the Institute for Health Research, Epidemiological Surveillance and Training in Dakar, which hopes to become a hub for health research, surveillance, and training in Africa.
Feature Image: Richard Marlink (right), a Harvard physician in the Senegal study, greets a patient in Dakar.