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Story Publication logo November 13, 2008

University of Minnesota Doctors Battle AIDS in Uganda


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Dr. Michael Ssonko, left, and Dr. David Boulware study an x-ray of an HIV patient. Image by Sharon Schmickle. Uganda, 2008.

Costa Kiggundu had one question for an American visitor to her home in a gritty Kampala slum: "What will happen if you stop sending the drugs?"

It's a life-or-death question for Kiggundu, her son and all of her friends at the clinic where she gets medicine to help her body fight HIV infection, which killed her husband.

Thanks to President Bush's drive to combat HIV/AIDS, the United States is sending the life-saving medicine to Kiggundu and nearly 2 million others across sub-Saharan Africa. No nation has made a larger commitment to fighting a single disease than the United States has made under Bush's leadership.

But as Bush prepares to leave the White House, he also leaves America with a solemn responsibility to follow through on the treatment.

Writing the checks was only a first step. Now a critical next step is underway: building a web of African-American expertise and facilities to ensure that the medicine is used effectively and continues to reach Kiggundu and others who need it.

This story follows one thread on that web — University of Minnesota doctors working side by side with Ugandan physicians.

Their experience illustrates the enormity of the challenge: They are grappling with an unexpected complication which threatens to jeopardize a good share of the benefit America intended by sending HIV therapy in the first place. Paradoxically, the patients risk a deadly development in the rollout of the medicine in Africa.

The story began in 2003 when Dr. Paul Bohjanen came to Kampala to help train African physicians in the use of HIV medicine. Bohjanen brought the wisdom of experience because he treats HIV/AIDS at the University of Minnesota Medical Center. He also co-directs the university's Center for Infectious Disease and Microbiology Translational Research.

In Uganda, Bohjanen met the full brutal force of the HIV pandemic. It had killed nearly a million people, one in every 27 Ugandans. A million more were living under its death sentence. Their only hope for a reprieve was in HIV drugs, which were just beginning to trickle into sub-Saharan Africa.

Never had Bohjanen felt greater urgency for his service as a doctor.

"I was really hooked by the tremendous need," he said.

The awful weight of that need was overwhelming Dr. David Meya and other Ugandan medical workers. Meya is a fellow at Makerere University's Infectious Diseases Institute in Kampala where a seemingly endless river of HIV/AIDS patients streams through the doors.

Slipping backwards

Bohjanen and other U.S. experts were more than welcome.

As the doctors pitched in together to save Ugandan lives, though, they hit an unexpected road block.

"A lot of the patients were getting worse instead of better," Bohjanen said.

Even while immune systems were recovering, nearly one third of the patients paradoxically were slipping backwards.

Doctors in Kampala were among the best trained in Africa by this time. But they carried staggering caseloads. Where would they find the resources to sort through this disturbing development?

Back in Minneapolis, Bohjanen recruited a colleague, Dr. David Boulware. The University of Minnesota's Academic Health Center contributed $200,000. More funding came from a philanthropic arm of the company Tibotec and the U.S. National Institutes of Health.

Boulware and Bohjanen boarded plans for Kampala two or three times a year, staying two to four weeks at a time. Students and fellows from the university's schools of medicine and public health filled gaps between their shifts.

A first step was to track patients getting antiretroviral drugs and mark the differences between those who got better and those who didn't.

Kiggundu was in the lucky group.

She is thriving under the therapy, with plenty of stamina to mix the boiled water and pineapple juice she peddles for a living on the unpaved streets of her neighborhood.

Life had been tough since Kiggundu's husband died of AIDS in 1990 leaving her with six children. She made a home in a shantytown section of Kampala where corrugated tin, wood slats and cardboard hold together a patchwork of houses and ramshackle shops. During the rainy season, flood water gushes into her house, carrying disease and dirt from the streets.

The result from her own HIV test — positive — was just one more development she was powerless to fight.

"There were no care centers, no place to go when you felt sick," she said.

So she carried on amid the sickness and death the pandemic had visited upon Uganda, putting her own fate out of her mind.

What shook her complacency was the result of her son Derek's test in 2006: positive, too.

"That's when I really lost hope," Kiggundu said.

But for the first time in two decades hope was beginning to take hold around her.

The Infectious Diseases Institute, on a hill overlooking central Kampala, was among the first in sub-Saharan Africa to launch a large-scale HIV/AIDS treatment program.

Costa and Derek, now 15, joined the first wave of patients and the first chapter of Africa's success story.

Medicine backfiring

Richard Myimbwa is another story, though.

Once a robust motorbike taxi driver, he was so gaunt his belt wrapped almost twice around his waist when his brother brought him to the Institute for a recent checkup.

Myimbwa, 27, weighed in at 132 pounds. He reached into a yellow sack and pulled out bottles of pills he was given courtesy of the U.S. program called the President's Emergency Plan for AIDS Relief, or PEPFAR

Meya, the Ugandan doctor, counted the pills left in the bottles to make sure Myimbwa had taken the right number.

He had. But the medicine seemed to be backfiring.

In HIV patients, the virus infects cells in the immune system. Once established inside a cell, it makes copies of itself and dispatches them to other cells. Left unchecked, it would invade enough cells to slowly destroy the immune system and open the patient to deadly invasions of diseases and cancers.

The antiretroviral drugs don't cure anyone of HIV. Instead, their job is to interfere with the way HIV copies itself and spreads from cell to cell. That secures the ability of healthy immune system cells — most notably, a type of cell called CD4 — to guard against diseases.

Meya combed through Myimbwa's file.

"He had been doing pretty well," Meya said. "The amount of the virus in his system was down. His CD4 count was up."

But after six months on the therapy Myimbwa was sliding mysteriously downhill.

He appeared to have meningitis and tuberculosis.

Classic pattern

It was the classic pattern of the problem the Minnesota and Uganda doctors set out to solve.

"In the rollout of HIV therapy here, some things have gone gloriously well," said Boulware, who was working in the clinic that same day and conferred with Meya about Myimbwa's case. "And then there are some unexpected challenges."

The challenge in Myimbwa's case appeared to be something doctors call immune reconstitution inflammatory syndrome or IRIS. As his immune system recovered, it had charged into overdrive, setting off inflammation and other problems.

In the United States IRIS is rare. Here in Uganda, where the therapy started later, it is showing up in one of every three people who start HIV therapy. The flare-ups range from mild skin infections to the life-threatening complications confronting Myimbwa.

"The point of our study is to learn why that happens and how to prevent it," Meya said.

In a scientific phase of the study, blood samples from Myimbwa and other Ugandan patients have been shipped to Minneapolis where they are analyzed for clues to the puzzle.

"We are looking at which genes are turned on and which are turned off," Boulware said.

Here in Uganda, the doctors have tracked hundreds of patients over time, comparing and contrasting various factors in successful cases like Costa Kiggundu and worrisome ones like Richard Myimbwa.

Many patients

There is no shortage of candidates for the study in the waiting room of the Infectious Diseases Institute.

At 2:30 on a typical afternoon, an electronic counter said doctors were ready to see the 244th patient of the day. All of the 150 chairs were full, dozens more patients rested on floor mats, and people kept coming in through the door. Some were grey-haired. Some were children. Many held babies.

Those who didn't see doctors that day would come back the next day and the next.

This clinic alone has 21,000 registered patients, more than have been treated for HIV/AIDS in all of Minnesota since the disease was first diagnosed. And these Ugandan patients represent a small fraction of Africa's HIV caseload.

Even after all of the deaths, 22 million people in sub-Saharan Africa were living with HIV in 2007, according to the Joint United Nations Program on HIV/AIDS (PDF). That was two-thirds of the global total.

Uganda has done better than most other African countries at acknowledging the problem, treating the infected and educating others to protect themselves by using condoms and abstaining from risky sex, especially with multiple partners. As a result, there's been a sharp drop in new HIV cases.

Ugandan president Yoweri Museveni gets a good share of the credit.

While some other African leaders were denying their nations had HIV/AIDS problems, Museveni was declaring war on the disease.

"When a lion comes to the village, you don't make a small alarm. You make a very loud one," he said at an African Development Forum in Ethiopia in 2001. "When I knew of this problem, I said we must shout and shout and shout and shout."

Shortage of medical facilities

The country's enlightened approach is a reason doctors from Minnesota and elsewhere brought their hands-on work here. With cooperation from local officials, they could do the most good for the most people.

For the same reason it also is the place where the IRIS problem has surfaced and been detected.

In studying the problem, the Minnesota-Uganda team is just now reaching the point where they have enough data to develop hypotheses about why IRIS is so prevalent, Boulware said. A next step will be to set up studies with other experts in different HIV/AIDS hotspots and test the theories.

Rather than a single cause, they are likely to find an array of reasons for the complications.

One suspect is the severe shortage of medical facilities and skills. Some patients could have escaped complications had they been able to get to clinics and hospitals and start HIV treatment earlier, Bohjanen said.

And so another part of the study is focused on improving health care through intensive training at the Infectious Diseases Institute and Mulago Hospital, which is just across the street.

Anyone who has seen the movie "Last King of Scotland" has seen Mulago Hospital in dramatic scenes depicting the brutal reign of former Ugandan dictator Idi Amin. One pivotal scene is from the hospital's rooftop, which gives an expansive view of Kampala and also a platform for watching buzzard-like Maribou storks shift from tree to tree.

At ground level, the hospital is a beehive of activity. With resources stretched to cover medical necessities, there is little left for bedding and food. So patients' families move into the wards to serve meals and change bedding. Many relatives sleep on floor mats between the hospital beds. On the sloping back lawn, they launder bedding and stretch it out to dry in a colorful patchwork symbolizing love, duty and worry.

More than 1,200 health care workers from across Africa have trained here where Bohjanen now is a professor in residence.

Boulware and Meya recently walked a group of Ugandan trainees through rounds in the infectious disease wards.

'You are not spectators here'

At each bedside, they encountered problems the Minnesotans were here to address.

One tiny, frail woman sat on red satin sheets while Boulware and Dr. Michael Ssonko studied her chest x-rays for reasons she had been wracked by coughing and fever. It could have been pneumonia, but it looked more like tuberculosis, Boulware said.

In the next bed, a woman moaned quietly while her husband tried to comfort her. Despite HIV drugs, she'd had seizures, raging fever and headache so severe she could not bear to open her eyes.

In the male ward, they saw three patients with cryptococal meningitis, a dangerous infection of the lining of the spinal cord and brain. Another man's feet were blotched with the cancerous lesions that sometimes attack HIV/AIDS patients. Yet another's liver had turned so toxic he had to stop taking HIV drugs.

Meya and Boulware lectured young doctors in their bed-to-bed entourage, urging them to engage more aggressively at earlier stages of their patients' battles with HIV/AIDS.

"You are not spectators here," Meya said sternly.

The lesson was coming too late, though, for most of these patients. They will die.

The latest thrust by Minnesota doctors is to try to intervene before patients are in such desperate straits. They recently secured a planning grant from the U.S. National Institutes of Health for a five-year project that will be based in Uganda and South Africa.

Meanwhile, it is sobering to think that this setting in Uganda is as good as it gets in Africa — that to leverage full benefit from America's investment in HIV drugs, the work started here must be repeated in cities and villages across a continent that struggles with so many other problems.

Taking a break on a patio outside the hospital, Boulware pondered Kiggundu's question: "What will happen if you stop sending the drugs?"

"This is a huge burden that is not going to go away," he said.


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