The Temporary Miracle

In its relentless, decades-long march across the world, HIV has killed 25 million people. One region has suffered more than any other: sub-Saharan Africa. The region is home to over 60 percent of the 40 million people now living with HIV, according to UNAIDS. Of the 3.1 million AIDS-related deaths in 2005, more than two-thirds—2.4 million—occurred in sub-Saharan Africa.

For most of the epidemic's first two decades, HIV infection proved a death sentence. The retrovirus known as HIV would spend 10 years or more knocking off the immune system's critical CD4 cells. Meanwhile, the infected person could unknowingly transmit the virus to others. Finally, the person's immune system would collapse and the body would be overwhelmed by opportunistic infections like tuberculosis, pneumonia or diarrheal disease. Health workers could only treat the symptoms until the patient died, and the bed was claimed by the next person.

Effective antiretroviral (ARV) medications like highly active antiretroviral therapy (HAART) became widely available in the West in the late 1990s and now offer hope to HIV-positive Africans. Though they may cause side-effects like skin rashes, potentially life-threatening hepatitis, nausea, headaches, hypertension and so on, the drugs keep the virus at bay and allow HIV-positive individuals to return to an almost normal life. In wealthy countries, the drugs have almost shifted HIV to the status of a manageable, chronic disease like diabetes. And in the world's developing countries, ARVs have brought great optimism. But that hope is tainted by the fact that ARVs are not a cure but a means of prolonging life. Other realities intrude as well: Cost (from $300 to $1,000 per year in developing countries, depending on the type of drug and amount of monitoring) remains a major hurdle, especially in those developing countries where annual per capita health spending may only be $6 to $10. Distribution, supportive care and the swelling numbers of people who will need ARVs each year further diminish their potential as a long-term, widespread solution. UNAIDS estimates that "at best" only one in 10 Africans who needed ARVs was receiving them in mid-2005.

On this warm January day in the Ugandan countryside, however, financial and logistical issues matter little to Yosam Katongole. He just wants to stay alive. So he has come with his wife and daughter to a mobile ARV clinic established by the Rakai Health Sciences Program.

Through collaboration and support from the National Institutes of Health (NIH), the Bloomberg School, Makerere and Columbia universities, the Bill and Melinda Gates Institute for Population and Reproductive Health, and others, the Rakai program has transformed the science of HIV by providing key insights into HIV transmission and prevention (see sidebar). Bloomberg School professors Maria Wawer and husband Ron Gray have long collaborated with their Ugandan colleagues on the program. Fourteen Ugandan investigators have earned master's or doctoral degrees at the Bloomberg School. And another three dozen have trained at the School. 

Although research has always been the program's main focus, its leaders also felt an ethical obligation to do more than just collect blood and data from the people of the Rakai district. "We are part and parcel of the community," says David Serwadda, founding Rakai principal investigator and director of the Institute of Public Health at Makerere University in Kampala. In addition to following a 12,000-member cohort, the program runs a mobile clinic that dispenses medications in rural areas, offering treatment for malaria, respiratory infections and other common illnesses. "We helped put in a pediatric ward at the hospital and built health centers. We've helped to finish roofing a school. That way the community feels you're interested in their welfare," says Serwadda, MBChB, MMed, MPH '91.

Since the early 1980s, when Rakai emerged as the epicenter of Uganda's HIV epidemic, the virus has cut a merciless swath through its population: From 1994 to 1998, 75 percent of adult mortality was attributable to HIV, according to one Rakai study. The funding that the Rakai program has secured has been largely for research, not treatment. So when George W. Bush announced his five-year, $15 billion President's Emergency Plan for AIDS Relief (PEPFAR) program in 2003, the Rakai program quickly applied for funding for ARVs. It began distributing the drugs in June 2004.

On this January day, the Rakai mobile ARV clinic has landed in a cement building outside Lwamaggwa. Inside, the walls' lower four feet are painted gun-metal gray. Above, dull white. Women wearing dresses of indigo, copper, scarlet and lime sit on wooden benches. Children play outside as nurses interview patients. A sick man lies on his side in one of the two beds. He does not move.

Gertrude Nakigozi, the physician in charge of the mobile ARV clinic, threads her way through the people, consulting with a nurse, drawing blood from a woman and chatting with clients. A lemon-colored shirt collar sprouts from her white lab coat. Her hair is corn-rowed and flows back into a clipped ponytail of unbraided, cinnamon-tinted hair. Long familiar with the soul-trying work of tending patients with AIDS, she displays an uncommon grace and equanimity. In the last year and a half, her rounds have been sweetened by hope. "Before ARVs, patients didn't improve. You would feel frustrated and wonder if your judgment was really right. And now, some of those on ARVs come in with no complaints. They just want their ARVs," she says. "On our side, you really feel satisfied you are making a difference in their lives. You get the patients out of bed, and they are fully up and working." 

Like Nakigozi, ARV clinic physician Ronald Galiwango relishes the Lazarus-like transformation afforded by the ARVs. "People come in in a very wasted clinical state. They have so many infectious illnesses and their quality of life is not good at all. They come in hopeless. They don't think they can make it. Maybe in two months, they are totally different. They can work and tend their garden. It's good to see people really change, people who had no visions or dreams."

This is the miracle that Yosam Katongole seeks. But like many other men with AIDS, he has put off seeking medical attention. ("Men often present at the ARV clinic late—when their chances of getting better are much lower," says Nakigozi.)

Katongole, weak and emaciated, sits on a hill outside the clinic and talks about HIV. Burdened with worry and perhaps pain, he furrows his brow and smiles rarely. Katongole says he wasn't surprised in January 2005 when he learned he was HIV positive. He had been feeling ill for a long while. And in rural Uganda, AIDS is all too common. (HIV prevalence among the Rakai program's 12,000-person cohort is 11 percent.) Throughout 2005, he continued to lose weight and strength. By the year's end, he could no longer do the heavy work on his small farm and banana plantation. His children do some, but mostly his pregnant wife does the work. She began taking ARVs several weeks previously. "She has improved each week that passes since she started ARVs," Katongole says. (His children's HIV status is not known at present. Before the advent of preventive treatments such as Nevirapine, 25 to 35 percent of HIV-positive mothers passed the virus to their infants. In Uganda, 84,000 children are HIV positive, according to UNAIDS estimates.)

With his antiretrovirals, Yosam Katongole receives something else: a warning. He will have to take the drugs for the rest of his life.

With the new medications, Katongole—like all the other patients at the ARV clinic—receives something else: a warning. He will have to take the drugs for life, but Rakai's PEPFAR funds have been committed only through March 2008. "They ask, what happens then? We tell them having some drugs and living today is better than dying today," says Nakigozi. Patients are assured that every effort will be made to continue the program for as long as possible. However, future ARV availability will depend on U.S. government renewal of PEPFAR or on the Rakai program's ability to secure other funding.

"You know it is very hard. Once you have these patients, they are on for the long-term," says Serwadda. "That is a much greater worry to me than even getting funds for research: the social responsibility for these people. Where are the funds for sustainability?"

The question is not an abstract, what-if for Scovia Ssegayi, an HIV-positive patient at the ARV clinic in Lwamaggwa. The PEPFAR-funded ARVs have given life back to her and many of her friends. "In the past we were so weak, we could not even take care of the children," she says. "Off and on, we were bedridden, and now we can contribute to our development." Ssegayi appears entirely healthy: her face almost plump, her arms muscled, her hair brushed back in a chic coiffure. She wears a stylish, long dress patterned in burnt orange and black. A widow, she sells beans, maize and sweet potatoes from her farm nearby to support her four children, ages 18, 14, 11 and 7. She knows she needs the drugs to live. And she knows her supply is not guaranteed. 

"If the program stops," she says, without emotion, "we shall be looking at our graves."

ARVs are potent drugs, and the patient's health must be followed closely for dangerous side effects. "If they don't die of the disease, they might die of these drugs," says Taha Taha, a Bloomberg School professor of Epidemiology who has led a major HIV research program in Blantyre, Malawi, since 1992. "These drugs, you can't use them like 10 tablets of chloroquine for malaria. We can't use these drugs indiscriminately. These drugs require discipline."

Patients must take anywhere from one to three pills twice a day. In the first few weeks of ARV therapy, they often feel worse before getting better. Their blood must be tested regularly to monitor their immunity and the effectiveness of the drugs. "A CD4 test costs at least $15. Even if you use only one of these a year, we're still talking about more than what the ministry of health can afford," he says. In Malawi, only about 2,000 people are on ARV treatment despite an adult HIV prevalence rate of 16 percent, says Taha, MBBS, PhD '92, MPH. 

A paucity of trained health workers also hinders attempts to administer nationwide programs. In many African countries, the ranks of physicians, nurses, laboratory technologists and other health workers have been ravaged by the AIDS epidemic and further thinned by the "brain drain" to the West. Malawi, for example, has just 250 physicians to serve 12 million people.

Like many others in Africa, Yosam Katongole isn't threatened just by the virus that causes AIDS. With his first month's supply of ARVs, he will also receive a large cardboard box. Inside are a jerry can and a filter for treating water to avoid diarrheal diseases and two mosquito nets to fight off malaria. These and other health threats like acute respiratory infections vie for attention and resources in Africa. "For ministries of health, these are competing priorities," says Taha. "Should they make all resources available to HIV and not cover immunizations? What about the people who come to the hospital with injuries? Shouldn't they be operated on? There are other health problems too: safe water, nutritional supplementation and sanitation. Governments have got very finite resources to cover them."

The difficulties convince Taha that simple, sustainable ways of preventing HIV transmission are essential. In Malawi, Taha and colleagues still encourage men to use condoms but they also study the effectiveness of methods such as vaginal microbicides and the use of antiseptic wipes by men before and after sex.

For most HIV researchers, ARVs are clearly not the solution to the AIDS epidemic. "It's just simple arithmetic. You look at the people infected now and project forward 10 years," says Ron Gray, MBBS, MSc, the William G. Robertson Professor of Reproductive Epidemiology. "If we cannot prevent new infections, the mortality consequences and the treatment load are going to be devastating." In Rakai, for example, 510 people are currently being given ARVs. And every year, researchers expect that number to increase by 10 percent. Rakai researchers believe that sometime in the next year or so they will no longer be able to enroll new people in the ARV program. "We are going to face the ethical dilemma of turning people away," says Gray resignedly. PEPFAR's recent approval of the use of less expensive generic drugs means more people can be enrolled in ARV programs. (Previously, only approved, brand-name drugs were funded by PEPFAR.) But even with the growing use of generics, demand will far outstrip supply.

ARVs have another downside: More drugs do not necessarily translate to less disease. Researchers worry that the mere availability of ARVs will alter people's behavior. The change in attitudes in developed countries following the widespread availability of ARVs is not encouraging. "It was a naive assumption that having access to treatment would mean that HIV's spread would decrease," says Chris Beyrer, associate professor of Epidemiology and director of the Johns Hopkins Fogarty AIDS International Training and Research Program. "In fact, there is some evidence that the opposite has happened. The next generation of people come along and don't see a lot of death. Some at risk for infection may not think there's much to worry about."

Beyrer, MD, MPH '90, puts the conundrum in dueling sociological terms. "Treatment optimism" (when the introduction of a viable therapy reduces your concern and caution) can trump the "funeral effect" (once you've gone to 10 funerals linked to a certain behavior, you change your behavior).

The likelihood of treatment optimism makes Maria Wawer, professor of Population and Family Health Sciences, uneasy about ARVs' effects in Rakai. In a 2005 study, Wawer and her colleagues warned that current behavioral trends indicate that rates of HIV may soon be increasing. "The improvements seen up to now in Uganda's HIV epidemic may not be sustainable without major new prevention efforts. We should not be complacent. It's not as if the HIV story is over," cautions Wawer, MD, MHSc. 

"We are truly at a crossroads," says Serwadda, a key player in Uganda's fight against AIDS since the early 1980s. Serwadda sees ARV therapy as either presenting a great opportunity to reduce HIV or leading to a complacency that masks the epidemic's true nature and allows it to become much worse. "If we can invest in prevention, then we have a chance that we may actually reduce both incidence of the disease and make a dent in the epidemic," he says. "I really don't think we have invested in ARV education in Africa the way we should have, and there isn't a good companion program at the moment in monitoring resistance. That is the capacity we're starting in Rakai." 

As Steven J. Reynolds, MD, MPH '02, scientific director of NIAID's International Center of Excellence in Research based in Rakai, puts it, "ARVs are one component, but they are not going to miraculously eliminate the epidemic. Our efforts still need to focus on prevention as well."

ARVs are an expensive way of buying time, keeping people alive while research in Rakai and elsewhere continues. As Wawer says, research is the only way to track the epidemic, identify risk factors in HIV acquisition and transmission, find weaknesses in the virus and ways to strengthen the human immunological defenses against it and test promising prevention and treatment methods. 

For Yosam Katongole, prevention research offers hope for his five children, but not for him. He says he talks openly with them about HIV. "I don't hide anything. I tell them everything about HIV. I tell them they can only prevent HIV if they use condoms or if they go for HIV testing before getting married," he says, pulling at the grass in front of him. "I don't know how I got HIV. I didn't have so many sexual partners."

He suffers a brief coughing fit, turning his head to the side and muffling it with his left hand. Then he talks more about his plans for his kids, his hope that they will not join the 940,000 Ugandan children orphaned by the AIDS epidemic. "I've bought land for my children. I've built a house for my children. I'm trying to educate them as long as I'm still living," he says. 

Before rising to make his long journey home, Katongole ponders his situation a few moments more. Then he confesses, "I need prayers from so many people."

Not all the prayers for Yosam Katongole are answered.

A few weeks after commencing antiretroviral therapy, he suffers bouts of severe diarrhea and is admitted to a Rakai hospital. His health improves briefly, but he dies on February 17.