AIDS: Finding answers

Ampheletse Medupe’s headaches just wouldn’t go away. Living in her small, neat home outside the African nation of Botswana’s capital, the mother of four kept on as best she could until sores broke out on her face. Finally, she visited a doctor.

Then came the bad news.

Her doctor told her that the unusual skin condition was caused by the herpes virus and likely tied to an HIV infection. HIV, the virus that causes AIDS, attacks the immune system and allows illnesses that the body would otherwise control to become far more serious. On her doctor’s recommendation, Medupe went to the government-run Princess Marina Hospital in the capital city of Gaborone to be tested.

There, Medupe’s fears were confirmed. Relief, however, was not on the way. Though she was infected with HIV, her illness wasn’t severe enough to qualify her for the drugs that might control the virus. She was sent home until she got sicker.

“I was in terrible pain,” Medupe recalled recently.

Several years later, in 2002, her nurse mentioned that a new study was being conducted by the Botswana-Harvard Partnership, a collaboration between the Harvard School of Public Health’s AIDS Initiative and the Botswana Ministry of Health. The Tshepo Study, named for the word “hope” in Setswana, the local language, would provide a research foundation for a national antiretroviral drug distribution program. The program was one of the first in Africa and put Botswana far ahead of most other countries on the continent in dealing with the spread of HIV.

But before results would inform national policy, the study trial provided antiretroviral drugs to Medupe, an act she believes saved her life and allowed her to become active in promoting AIDS awareness. Today, she works with a small group of women to make beaded AIDS pins that are sold internationally to raise income and increase awareness of the problem.

And the problem is severe. AIDS is the top cause of death in Botswana. HIV seroprevalance rates in adults were at 37.3 percent in 2003, indicating that the disease afflicted more than a third of the nation’s 1.7 million people. Infection rates in some areas were far higher, however. In the hardest-hit area, Selebi-Phikwe, 52 percent of pregnant women were infected with HIV in 2003.

There are signs that the epidemic is slowing. HIV infection rates were down nationwide to 24 percent, according to a 2005 survey, though they were still severe. Among Selebi-Phikwe’s pregnant women, for example, HIV infection rates in 2005 were found to have fallen to 46.5 percent. Life expectancy, which had fallen from 64 in 1990 to 40 in 2002, rose to 50 in 2007.

The Botswana-Harvard Partnership has helped guide the government’s actions against the epidemic since the partnership was founded in 1996. It is headed by Max Essex, the Mary Woodard Lasker Professor of Health Sciences and chairman of the Harvard School of Public Health AIDS Initiative. Essex said the effort, which involves eight or nine Harvard faculty members, got started after then-President Ketumile Masire invited him to visit Botswana to talk about working together against AIDS.

The work of Essex and the Harvard School of Public Health AIDS Initiative is just one example of an enormous and diverse body of global health research, education, and training across Harvard. Harvard researchers toil away to understand everything from the genetic code of the malaria parasite to the impact of air quality on human health, instructors impart the latest in medical knowledge to top students, and colleagues at Harvard’s many affiliated institutions not only teach and conduct research of their own, they also put that knowledge into action to improve people’s lives — in Boston and around the globe.

Essex is an appropriate head for the Botswana effort. Despite a low-key personality, his research has again and again shed new light on the HIV virus almost since the epidemic began in the early 1980s. Among the discoveries by Essex and colleagues is that HIV can be transmitted through blood products to hemophiliacs. They also discovered the definitive diagnostic test to screen blood intended for blood banks and that the disease can be transmitted through heterosexual sex. Essex also identified important surface proteins on the virus; discovered a less virulent type, HIV-2; and also discovered the African monkey analogue to HIV, the simian immunodeficiency virus.

The partnership oversaw construction of a modern laboratory dedicated to HIV research, the Botswana-Harvard HIV Reference Laboratory, located on the grounds of Princess Marina Hospital in Gaborone. The laboratory, which opened in 2001, provides a scientific anchor for research into AIDS in the hardest-hit region of the world: southern Africa.

The facility hosted the first HIV vaccine trials in southern Africa — which were ultimately unsuccessful — and today focuses its efforts on research aimed at understanding the virus and developing better ways to control it. It also houses laboratories that process thousands of blood samples to help the government manage the epidemic and works to train health care workers who fan out across the nation in an effort to stem the epidemic’s tide.

“We’ve made huge progress in defining how best to treat people, to save lives, and how to use ARVs [antiretroviral drugs] to block transmission,” Essex said.

Among the research efforts under way today are trials to better understand mother-to-child transmission of HIV, the effects of micronutrient supplements on disease progression, and whether suppressing herpes can limit HIV transmission in couples; and on developing the best combination of drugs to treat women who have previously been exposed to the antiretroviral drug nevirapine.

“We’ve made a lot of progress identifying which drugs work best and how to prevent resistance from occurring,” Essex said. “We just started a new genetics study to look at not just drug efficacy, but [how genetics affects AIDS] risk and disease progression.”

Clinical trials occur at Princess Marina Hospital and at satellite clinics in surrounding communities that make it easier for subjects to participate without having to travel far from home.

While work seeking a vaccine against HIV continues at the lab, Essex said that last fall’s results from an unsuccessful vaccine trial in South Africa, conducted by the Merck pharmaceutical company, brought vaccine research back to square one. The results, which Essex termed “disastrous” because of the possibility that the vaccine might have been harmful, invalidated a common approach to vaccine creation used in many labs.

In a talk in January to staff at the Botswana-Harvard HIV Reference Laboratory, Essex said that though efforts would continue, new approaches would have to be pioneered, meaning other candidate vaccines would not be ready for testing for several years.

The reduced prospects for a vaccine make the partnership’s efforts to support the Botswana government’s treatment and prevention efforts even more critical.

One key way they do so is by providing in-service training through the KITSO AIDS Training Program. Kitso is the Setswana word for “knowledge” and also forms an acronym in English that stands for “Knowledge, innovation, and training shall overcome.” The program, conducted in collaboration with the Botswana government, has become Botswana’s national training program for HIV and AIDS and provides medical professionals across Botswana with a standardized course of training in HIV and AIDS care.

Program Manager Christine Bussmann said that when KITSO began in 2001, there was no in-service training for health professionals in Botswana. Making matters worse, HIV and AIDS were only poorly covered in pre-service training, such as medical school and nursing programs.

“There were very few people who had dealt with AIDS, maybe a couple hundred in the whole country,” Bussmann said.

The program began with training on how to diagnose HIV and how to counsel patients before and after a diagnosis. Soon, the government asked that the program offer training on other topics, such as administering antiretroviral drugs.

Today, KITSO has expanded to include units on opportunistic infections, drug resistance, HIV/tuberculosis co-infection, pediatrics, and other topics. All together, the programs have trained more than 8,000 people and continue to educate both first-timers and those who need a refresher.

“We recently had a long-term evaluation of our training program, how it’s impacted health care workers,” said Elang Mabe, KITSO’s program coordinator. “The majority of people feel the training helped or improved statistics of HIV/AIDS in Botswana.”

KITSO has been successful enough that turnover has become a problem among Botswana’s health professionals. KITSO certificates awarded at the end of training are looked at favorably by potential employers working on AIDS in Africa who hire Botswana’s health professionals to work in other countries.

The Botswana-Harvard Partnership not only trains health care workers, it also seeks to increase the ranks of the nation’s scientists. The Botswana-Harvard HIV Reference Laboratory provides a research home for scientists working in Botswana and acts as a hub for Boston-Gaborone exchanges.

“Most of us believe the biggest long-term impact in turning around the AIDS problem in Africa depends on bringing in lots of new young people who can devise new strategies,” Essex said.

Several doctoral students and postdoctoral fellows work at the lab, some of whom are in Gaborone after spending years at American universities, including Harvard.

Keikantse Matlhagela, a postdoctoral fellow at the Botswana-Harvard HIV Reference Laboratory, said she believes research such as her own into HIV virus transcription is vital, but that training people at all levels about the disease is also crucial.

Matlhagela called the Botswana-Harvard Partnership a “dream come true” that provided a new intellectual home for her when she finished her studies, which took her to the State University of New York, Buffalo, and then to Essex’s lab in Boston.

Matlhagela’s international travel provided her a stark window on the disease’s effects over time and a determination to work to stem the epidemic’s tide. She initially attended college in the United Kingdom and, when she returned to Botswana in 1995-96, she saw friends she hadn’t seen in a while.

“You see someone you haven’t seen for some months, and they were very emaciated,” Matlhagela said. “Some family — cousins — died of AIDS; people that I knew, people that I knew truly well.”