American Foundation for AIDS Research, January 2001
Emily Bass

"I'm an old Ugandan right now," says David Serwadda, "I'm not that enthusiastic about treating with HAART." As he speaks, Serwadda looks out the window of the white four-by-four that is bouncing at high speed along the road to Rakai, a southern district that shares a border with Tanzania. Serwadda has been making the trip to Rakai since 1988, when the disease known as "Slim" was first reported. Back then, Serwadda drove from village to village, looking for people who fit the new condition's clinical description. What he found moved him to action. With the help of colleagues from Columbia University, Serwadda and a team of local Ugandan researchers established the Rakai cohort. For the last 12 years, data from the cohort has tracked prevalence, incidence and likelihood of transmission in the cohort's 17,000 participants, many of whom rely on the Rakai Project's mobile units for basic health care.

From where Serwadda sits, antiretrovirals are not the answer to the health-care problems facing the rural community he has worked o many years. Yes, he and his colleagues have had to explain many times that the "miracle drugs" the villagers have heard about do exist but are not available to them at the moment. But he is not convinced that they are the answer to the villagers' problems. Noah Kiwanuka, the Rakai Project field director, echoes Serwadda's concerns. "As a physician and as an Ugandan, deep down in my heart I would prefer that every HIV-positive person get access to antiretrovirals. On the other hand, there are a lot of other issues-before you even get to cost."

It isn't coincidence that both Kiwanuka and Serwadda invoke their nationality as they explain their approach to treating HIV. Geographical, economic and social differences between and within countries create wide variations in the "best practices" needed to fight a single virus. The Ugandan situation, as Serwadda sees it, must be defined by the diseases that are actually killing people with HIV. In the Rakai cohort, mortality in HIV-infected individuals is ten times that of their HIV-negative counterparts. Of these, however, only three percent die from AIDS-defining illnesses [such as CMV and toxoplasmosis.] "The environment is so full of virulent bugs that you just dip your immunity and they overwhelm you," says Serwadda. "Those that do [die of OIs] are the few that die of HIV-related infections. But a lot die before they get there." Instead of tackling the complex task of administering antiretrovirals, Serwadda would like to see research into simpler solutions, such as treating malaria as a means of reducing viral load.

Back in Kampala, the country's largest urban center, Peter Mugyenyi (see accompanying interview) worries that a focus on background infections, like malaria, may be distorted by those seeking to avoid the issue of providing antiretroviral therapy. "Tropical diseases don't choose countries. HIV does," he says, pointing to Senegal, the West African country that has managed to stall HIV prevalence at less than five percent, in spite of high rates of malaria. "It is not the tropical infections that are making HIV worse. It is the other way around."

When it comes to setting priorities for best practices, Mugyenyi and Serwadda again sound markedly different. Mugyenyi warns that most versions of OI treatment plans are a "soft option." Meanwhile, Serwadda says, "I'm more excited about opportunistic infections than I am about antiretrovirals. In terms of accessibility and affordability, OI treatment could actually be our HAART."

Their differences are, in many respects, more strategic than substantive. Serwadda and Mugyenyi are part of Uganda's close-knit team of researchers. Mugyenyi's Joint Center for Clinical Research does CD4 cell counts for some of the Rakai Project samples, and both men sit down regularly to hammer out the goals of the country's strategic plan on AIDS. The fact that that they do not, at the moment, share the same priorities does not signal fundamental disagreement. Instead, it is a reminder that, even in a country widely celebrated as an AIDS "success story," researchers are not pursuing one single goal, but rather a myriad array of objectives.

If anything, the common theme is a desire to up-end expectations about what can and cannot be done in Africa. For Mugyenyi, it is successful administration of antiretrovirals. For the Rakai project investigators, the victories lie in simpler strategies, like implementing self-administered vaginal swabs to diagnose bacterial vaginosis, a common infection which increases the risk of mother-to-child-transmission, or collecting placentas to gain data about infant health. "When I proposed this, people thought I was mad," says Rakai investigator Fred Wabwire. "In the end, 76 percent of women gave their placentas."

It is nearly impossible to meld these priorities into a single agenda. With an eye on the international audience, Mugyenyi is unwilling to compromise for anything less than HAART. Serwadda and the Rakai team are also looking for the best possible care for their cohort, and have grown adept at finding ways to do so. "After you are given money to run research, big funding agencies will not always fund to meet other challenges," says Serwadda. "The people you are dealing with are ill: 'Excuse me, I have malaria.'; 'Excuse me, I have pneumonia.' You have to be creative to get money to meet other healthcare needs."

In the end, both strategies-OI and antiretroviral-will have to be combined to create a truly effective, African standard of care. "There is no multi-pronged approach in [AIDS] funding," observes Serwadda. "It tends to swing in one direction, then another, then another. I would like HAART to be available, but I don't like to focus on it as the answer."

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