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Pick any of the 130 beds in the medical or pediatric wards of Botswana's Princess Marina Hospital and, odds are, the patient in it has an AIDS-related illness--according to hospital sources, up to 80 percent of the adults and about 30 percent of the children here are HIV positive. Just ten years ago, the southern part of the continent appeared to have escaped the virulence of the AIDS epidemic already sweeping through other parts of Africa. Today, however, countries like Botswana, Zimbabwe, and South Africa report some of the highest infection rates in the world. While relatively prosperous compared with some of their African neighbors, few inhabitants here have the money for expensive antiviral cocktails, and the only option for most doctors is to keep patients alive by fighting the opportunistic infections that come with AIDS. The physicians at Princess Marina are no exception.

However, now just a few steps away from these hospital wards, an earnest group of scientists is working to improve the way care is delivered in Botswana and countries similarly afflicted by AIDS. In February, after more than two years of planning, Botswana's Ministry of Health and the Harvard AIDS Institute (HAI) opened the Botswana-Harvard HIV Reference Laboratory--the country's first--on the hospital's grounds, bringing state-of-the-art research tools to the epicenter of the epidemic.

The new laboratory has multiple, overlapping missions. In addition to evaluating different approaches to treat people with AIDS, the researchers will test a theory about why the disease spreads so rapidly in these countries. Max Essex, chair of the Harvard AIDS Institute, has long attributed it to HIV-1c, a subtype of the AIDS virus he has discerned to be more virulent and infectious than HIV-1b, the form of the virus found in North America and Europe. In order to test which antiviral medicines and therapeutic regimes will best help the people here, scientists will need to understand the characteristics of this viral subtype, which dominates southern Africa and India. This information will also be essential to one of the lab's most ambitious goals--the creation of a vaccine for HIV-1c. "We're collecting a lot of viral samples and a lot of human blood cells to determine both the genetics of the virus and the immunologic status of infected people," says Essex. "By doing so, we can ensure that we design a vaccine that best matches the infection of the inhabitants here and has the greatest chance for efficacy."

In order to make best use of current technology to achieve their goals, the Botswana-Harvard team needed a sophisticated, on-site laboratory and a staff trained to run it. "Without a reliable molecular biology lab of this type, there are a lot of things you just couldn't do," notes Essex. For example, commercial labs can perform basic diagnostic tests like those that measure levels of cd4 immune cells, which are wiped out by HIV in the first month of infection. But they can't handle the more complex immune response tests necessary for vaccine development. Even if South African labs could carry out these kinds of procedures, the time necessary to ship the biological samples would make performing them worthless. "You have to do these tests within a day," Essex asserts. "You can't collect the sample and send it by air. Living cells stay alive longer than a day but [during that time] lose their ability for full responsiveness in the most delicate functions for demonstrating immunity." Establishing a fully operational reference lab right in the heart of Botswana's capital has overcome this problem.

It has also created visible ties between U.S. and African AIDS specialists. The offices of the Harvard AIDS Institute now bear the subtle signs of this tight collaboration. One of the clocks in Essex's office is set to Botswana time. A diagram on the blackboard charts out a planned lab expansion. A staff assistant fields calls from the Secret Service checking on the School's security before a planned visit by Festus Mogae, the president of Botswana. Even an unlikely connection between the Institute and the Miss Universe organization has resulted from the Botswana partnership. The 1999 winner of the beauty pageant, Mpule Kwelagobe, is a 19-year-old Gabarone local who has used her position to promote AIDS awareness. Kwelagobe was on hand for the Harvard-Botswana lab's dedication ceremony and has participated in Institute events both in the United States and in Africa.

While the new facility is dedicated to research and training, it will ultimately lead to better care for people in Botswana, according to Ibou Thior, an HAI researcher and the lab's on-site director. "The lab will play an important role in the fight against the HIV/AIDS epidemic," he says. "It will be a component of the capacity building process and will also assist other HIV/AIDS research projects, which will require laboratory support." For instance, the opening of the lab will pay off instantly for the thousands of people enrolling in the drug clinical trials now under way. Each participant will get antiviral therapies and follow-up care normally available only to the wealthy. And, treatments will not end when the studies are over but will continue for as long as the patients benefit, according to Howard Moffat, medical doctor at Princess Marina Hospital. Moffat also hopes that the studies will show that treating HIV-infected patients with antiviral drugs is more cost effective than simply treating the opportunistic infections or other manifestations of AIDS. "Then we will be in a strong position to advocate for provision of drugs through the government system," he says.

Currently, the laboratory is conducting two major studies, which also incorporate the efforts of scientists at the McGill University AIDS Center. The first study is using viral sequencing to try to trace the route of mother-to-child transmission of the virus; the second is looking at drug resistance. "The importance of this work is immense since HIV drug resistance is likely to be a growing problem in Botswana and other developing countries where sub-optimal therapy for HIV disease is the norm and not the exception," remarks Mark A. Wainberg, director of the McGill program and president of the International AIDS Society.

One of the questions the team hopes to solve is: why did HIV-1c, one of five of the major genetic subtypes of the virus, spread so quickly and become so dominant in countries like Botswana, Zimbabwe, and South Africa? One prevailing idea is that it simply spread to the general population first. An alternative theory that the laboratory in Botswana will test is that HIV-1c is more easily spread through heterosexual intercourse than other subtypes. HAI researchers believe that the HIV-1c virus has a high affinity for ccr5 chemokine co-receptors, which allow the virus to infect cells in the mucosal linings of the cervix and the vagina. In addition, because the HIV-1c type seems to have an extra length of the genetic code that governs reverse transcription--the process by which the virus invades healthy cells and duplicates--the team theorizes that perhaps more virus equals more disease.

Despite the challenges that face the new collaborative initiative, Botswana is a wonderful place to work according to Essex. "They have a very conscientious health care infrastructure," he reflects, "so it's much easier to follow people, monitor progress, and have faith that reasonable conclusions that would improve health care will be implemented. That's not the case in a lot of countries--whether or not they are developing countries--but it is true in Botswana."

Tinker Ready


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