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[This article was published in 2009 and updated in May 2012. Read the update here.]

In the late 1990s, the new effective HIV regimens remained largely unavailable in resource-poor countries. Global AIDS deaths among children under 15 amounted to almost 300,000 in 1999, and the number of newborns acquiring HIV in the same year exceeded 400,000. High-income countries contributed a miniscule amount to those figures because of their ability to administer antiretroviral therapy (ART).

Mark Kline, in 1995, was savoring his success in treating HIV at Houston’s Texas Children’s Hospital. Kline, a professor of pediatrics at Baylor College of Medicine, was pulled out of his complacency by a group of visiting Romanian doctors. While Kline talked to them about pediatric HIV care at the Children’s Hospital, his guests described the unique HIV problem in Romania. Some 10,000 neglected Romanian children raised in orphanages had contracted HIV due to hospitals’ use of blood microtransfusions to “fortify” their health. Not only was this practice medically unfounded, but the transfused blood was unscreened and the reused syringes unsterilized.

These children received little treatment, and the Romanian doctors were desperate. Kline returned the Romanians’ visit in February 1996. “I thought I had seen it all before,” Kline says now, “but I was not prepared for this. There were hundreds of stunted, wasted children with horrible open lesions. The kids had been warehoused in the AIDS ward and left to die. After two weeks in Romania, I thought, ‘My conscience can’t allow me to walk away.’ I developed the outline for an international pediatric program on the plane home.”

Kline started with a small amount of seed money but gradually built a public-private partnership that includes pharmaceutical company foundations, the United States and other governments, and international donors. The Baylor International Pediatric AIDS Initiative (BIPAI) now extends from Romania to nine countries in Africa (see map). As of 2009, it treats 30,000 patients. In developing this extensive network, BIPAI created an operational and financial model for bringing HIV care to resource-poor areas, something long considered impossible.

In the Beginning: Constanta, Romania

Kline’s initial visit centered on the Black Sea port city of Constanta. He was the guest of one of the local pediatricians, Rodica Matusa. The city was the focal point of Romania’s epidemic. At that point about 600 Constanta children had died of AIDS and another 600 were known to be HIV-positive. “We began a small program to examine the children and catalog their problems,” Kline recalls. “We treated their tuberculosis and diarrhea, gave nutritional supplements and started training medical personnel. We saw a modest improvement in health.”

Clearly more was needed. Matusa convinced her institution, the Constanta Municipal Hospital (since renamed the Infectious Diseases Hospital Constanta), to donate a nearby abandoned orphanage. Kline was able to secure initial renovation funding from a Houston-based religious order, the Sisters of Charity of the Incarnate Word. In addition, Abbott, the makers of HIV test kits and the popular HIV protease inhibitor Kaletra®, commenced its Step Forward program in 2000. Step Forward (managed by the Abbott Fund, the company’s philanthropic arm) focused on orphaned and vulnerable children affected by the HIV epidemic. Its first grant went to create the Romanian-American Children’s Center in Constanta, which opened in April 2001 with a Baylor and Romanian staff providing comprehensive medical and psychosocial services. For specialized HIV care, the center partnered with the government’s Infectious Diseases Hospital, whose providers Baylor helped train.

Summarizing Abbott’s early interest in the Romania-Baylor Project, Abbott Fund Vice-President Jeff Richardson says, “We heard from several people about Baylor’s outstanding reputation in pediatric AIDS. Kline was one of our consultants when developing the Step Forward program. We were impressed not only with his proposed care and treatment model in Romania, but also with his promise that Baylor would replicate this model in Africa.”

A steady source of antiretroviral drugs became available at the center in November 2001 when Abbott provided the Constanta patients with a lifetime no-cost supply of Kaletra. Kline was able to secure a stable supply of supporting nucleoside analogs through a Bristol-Myers Squibb donation. Later on, a grant from the Global Fund for AIDS, Malaria and TB allowed the Romanian government to become a reliable ART supplier. (At publication time, however, recession-induced budget cuts have created a looming shortfall in ART availability.)

Abbott also entered into an open-ended commitment to fund the clinic’s operating costs. With the clinic’s sustainability and access to drugs assured, annual mortality among the Constanta patients on ART progressively declined from 13 percent to 1 percent.

Aging patient population: The increased survival meant that the center was faced with a raft of new psychosocial issues. Ana-Maria Schweitzer is a Romanian psychologist who started working with the Baylor team in 1999 when all of the clients were under 18 years of age. She has since become the center’s director, and now almost all of the clients are young adults. Schweitzer says, “Before, the priority was to ensure survival. Now the daily needs are covered, including uninterrupted drug supply. The new priorities include informed decisions on pregnancy or becoming parents. Out of our original population, we now have 50 couples with children up to four years old.” The center provides its own obstetrics-gynecology and family planning specialists and social workers to provide care and counseling on the full range of family planning options plus preventing mother-to-child HIV transmission (PMTCT). So far, there have been no detected HIV transmissions to newborns.

A related issue is safe sex—counseling both the HIV-positive patients and their partners on preventing transmission, of which there have been suspected cases. Transmission as well as disease risk would decrease if everyone adhered scrupulously to their ART dosing schedules, but Schweitzer terms adherence “an everyday struggle” for adolescents. The center’s adherence support efforts include focus groups, counseling and home visits.

The biggest new challenge is helping HIV-positive young adults to become productive members of society. Says Schweitzer, “There was a lack of education: Nobody expected these kids to live, so many didn’t go to school. Those who did faced considerable stigma. So we help find jobs by acting as a buffer between our patients, job trainers and employers. We have special connections with employers that we have educated on HIV.”

Collaboration with government and international donors: The Constanta Center has been fortunate that the Infectious Diseases Hospital continues to partner with it as part of the national AIDS program. The increasingly capable hospital staff is in charge of ART treatment for the center’s clientele as well as for the rest of the local HIV population. This center, meanwhile, transformed itself in December 2007 into the Romanian Clinical Center of Excellence. It now welcomes all of Constanta’s 840 persons with HIV, adults as well as children.

As the center’s primary donor, the Abbott Fund regularly consults about the center’s accomplishments and further needs. It supported the expansion of social services while the government oversees HIV treatment. This pattern of tight cooperation with the local medical establishment and with funders became basic to BIPAI’s expansion to African locales.

Thinking Large: Botswana

U.S. pharmaceutical company Bristol-Myers Squibb (BMS) commenced its $150 million Secure the Future program in 1999 through the company foundation, just as the Constanta center was taking shape. Secure the Future was focused on southern Africa from the start. The BMS Foundation had worked previously with Mark Kline on the Romania clinic, to which it gave small cash contributions and drugs, and on training Mexican pediatricians. When launching Secure the Future, it immediately invited him to put together a new project based on the Romanian experience.

Collaboration with government and international donors: Far to the south of Constanta lies Gaborone, the capital of Botswana. Botswana has benefited from remarkable economic growth rates since independence and now has a per capita gross domestic product slightly higher than Romania’s. But with a quarter of its adult population HIV-positive, Botswana has a far higher HIV rate. Botswana’s government was also very supportive of bringing HIV treatment to its citizens. Its president, Festus Mogae, became personally involved in expanding treatment availability. A place like Botswana would naturally command Mark Kline’s interest.

Arguably, the government’s biggest contribution to BIPAI was Gabriel Anabwani, the chair of pediatrics at Gaborone’s health care centerpiece, Princess Marina Hospital. Looking back, Anabwani says, “We were so frustrated to helplessly watch children die in our hands when the treatments were out there.” He met Kline at a September 1999 BMS Foundation meeting. Kline visited Princess Marina Hospital, and the two put together a program of exchanges, training Botswana doctors in HIV treatment and U.S. doctors in opportunistic infections.

When Anabwani came to Houston for a month, he was impressed by how healthy the pediatric HIV patients were. They were living the lives of normal children. He wanted to show that African children could have a similar experience if ART were available. Secure the Future funded the initial Botswana-Baylor effort in this regard, which effectively became a 200-child pilot ART program. The research team worked out of a small trailer behind Princess Marina Hospital.

As the Botswana government prepared to introduce ART throughout the country, Kline and Anabwani floated the idea of a separate pediatric HIV clinic. With the president’s blessing, the Ministry of Health signed a memorandum of agreement to work with the project’s treatment, training and research activities. The agreement committed the government to providing antiretroviral drugs as well as land for the clinic on the Princess Marina grounds. Kline convinced the president of Bristol-Myers Squibb, Kenneth Weg, to have Secure the Future grant $6 million for the center’s construction and first five years of operation. Additional funding came from the U.S. National Institutes of Health and Centers for Disease Control and Prevention. “BMS agreed reluctantly,” Anabwani recalls. “Nobody treated HIV then; they only did prevention. Mark and I agreed that if the center failed, it would be fatal to attempts to treat children in Africa. We had a huge responsibility.”

Fortunately, the Botswana-Baylor Children’s Clinical Center of Excellence was a great success from the time it commenced operations in June 2003. BMS Foundation President John Damonti says, “It is the most beautiful building at the hospital. There was fear going in that parents would not bring their children to an HIV facility given the disease’s stigma. But they had 1,400 children on ART in the first year and 6,000 patients in the first two years. The center showed that the model works not just for training but also for catalyzing treatment and care.” Most critically, annual mortality among the patients fell from 4.7 percent in 2003 to 0.3 percent three years later.

Addressing the shortage of skilled personnel: Training other doctors is an essential part of the center’s program. “We have become a very valuable partner of the Ministry of Health,” says Anabwani. We provide all the training in HIV care for the whole country. We also sit on the health ministry’s key children’s health committee.” An international training program sends center doctors to other African countries for two weeks to one month.

Aging patient population: In 2009, the center had about 2,100 pediatric patients plus 260 families in its family care center. Botswana’s PMTCT program has proved highly effective, with transmission reduced to levels comparable to those in developed countries. As in Romania, the pediatric patient population is aging rapidly. “In three to five years, the majority will be adolescents,” Anabwani estimates. “We are advocating with the government, NGOs [nongovernmental organizations] and funders to sensitize them to teens’ needs.” In Botswana, too, ensuring adherence to dosing schedules is a big issue.

Safe sex is another looming problem. One advantage over Romania is that patients’ family structures are largely intact — and struggling with HIV together. Orphans are usually under the care of surviving family members. A major effort has been made to establish teen clubs and an annual vacation camp. Adolescents also are given more frequent clinic appointments with doctors specifically interested in adolescent care. “Our efforts need more development to be effective,” notes Anabwani. One of the remaining hurdles is transferring maturing patients to adult care. There are plans to ease the transition by bringing adult doctors to the pediatric clinic for extended periods.

New Frontiers

The BMS Foundation was so pleased with the Botswana experience that it moved to fund construction of six other clinics. The second Clinical Center of Excellence was located 300 miles (500 km) farther south, in Lesotho’s capital, Maseru. Lesotho has a population similar in size to Botswana, and its HIV prevalence is about the same, too. But Lesotho is considerably smaller in size and its economy much poorer.

Collaboration with government and international donors: The Children’s Clinical Center of Excellence in Lesotho commenced operations in December 2005 under a Memorandum of Agreement with the Lesotho government. There was only one pediatrician in all of Lesotho before the Center of Excellence opened. BIPAI brought in 10 doctors from the United States to provide sufficient pediatric care capacity. The government is paying for ART drugs and operating expenses with a grant from the Global Fund. UNICEF and private donors also underwrite various aspects of the operation. As of 2009, the center had 2,300 active patients, half receiving ART. Some 600 of the patients were adult family members of the pediatric patients. To alleviate Lesotho’s shortage of HIV care facilities, the Center of Excellence is constructing 10 satellite clinics outside Maseru to serve children and their families. The Lesotho government is providing the land and supporting the operating costs. Here too, the BMS Foundation is paying for construction while BIPAI will supply the staff.

Further expansion: The BIPAI network continues to expand elsewhere. It opened a Center of Excellence in Swaziland in February 2006 and in Malawi in November of the same year. In October 2008, BIPAI opened a center in Kampala, Uganda, the culmination of a hospital-based program that began in 2002. The Uganda center cares for 4,000 pediatric patients with 7,000 more receiving treatment at affiliated clinics in Kampala and around the country. As of 2009, Centers of Excellence were under construction in Burkina Faso, Kenya and two Tanzanian locations.

Swaziland’s center is building two satellite facilities, which are also planned for Tanzania. The BMS Foundation paid for constructing all but two of these sites, with international donors underwriting operational costs (principally the U.S. President’s Emergency Plan for AIDS Relief and the Global Fund). The Abbott Fund supplied the funds for building the Malawi center and largely supports its continued operation. It is also financing construction of one of the Tanzania clinics.

Addressing the shortage of skilled personnel: A shortage of doctors has proved to be a universal problem. “We found that it was easier to build centers than to staff them,” says Damonti. BIPAI announced in 2005 that it was organizing the Pediatric AIDS Corps, which Damonti’s BMS Foundation agreed to fund for five years. The program supports 50 or 60 doctors from the United States each year at the BIPAI clinics and at remote sites. The doctors participate in the centers’ care and training efforts for 12 to 36 months each. The Pediatric AIDS Corps is considered an interim measure until more African doctors are qualified in HIV care.

Keeping it all Together

In August 2006, BIPAI reported that it had less than 10,000 active patients; it reported an active caseload of more than 39,000 in October 2009. Kline has visions of eventually caring for 100,000 children with HIV—half the infected pediatric population in the countries with BIPAI clinics. The challenge will be to serve such a large patient body in a sustainable, well-organized fashion.
A major effort to ensure continuity is BIPAI’s Children’s Clinical Centers of Excellence Network. Supported entirely by the Abbott Fund, this network meets several times a year, bringing together a large proportion of the far-flung clinic staff. It plays a critical role in integrating their activities. In addition, Abbott and BMS see the meetings as another means to informally coordinate their activities with the network and each other—beyond these donors’ frequent site visits and personal communications.

The network also provides Abbott- and NIH-funded fellowships for study at the Baylor College of Medicine. The fellowships supplement the centers’ many in-country educational courses, and they are an effort to establish native leadership to oversee continued HIV care.

Yet troubles loom on the horizon. For example, the Pediatric AIDS Corps at present fills in the doctor gap, but the $22 million BMS grant that supports it ends in 2011. Either another funder will have to step in, or BIPAI will have to rely on the local doctors it has trained at that point. And where will the funds come for hiring more African doctors, whose expertise is also needed by nearby health care institutions?

One of BIPAI’s major strengths has been its strong cooperation with the national governments where it has operations. “We consider ourselves an extension of the national government HIV programs,” says Kline. “Our centers are kind of hybrids — they’re international but they have one foot in the Ministry of Health.” Kline believes that active government cooperation is critical. The governments cut through the ever-present red tape so that the centers can operate freely. They also support a substantial part of the centers’ operating expenses in several locations. If motivated, they might help pick up the tab at other locations that lose grant money.

It would, therefore, be a bad idea to hire doctors away from existing institutions. BIPAI has agreed to avoid that in every country in which it operates. It refrains from economic competition by paying at the local scale. But the centers of excellence offer other advantages.

Richardson notes, “Baylor is providing well-operated facilities that are attracting doctors back to their native countries or inducing local medical school students to stay. I hear from doctors and nurses that they want the tools to get the job done, and that this is at least as important as salary.” BIPAI endeavors to meet the demand for a quality professional environment through its training programs, lab facilities and computer technology.

In any case, Kline foresees a period of consolidation. No new clinics are under consideration. He says, “Our primary thrust will be to realize the centers’ full potential through extending pediatric and family care, professional development, satellite facilities and electronic health records. We are not growing the number of centers but concentrating on delivering the highest quality care and supporting the local health system.”

By David Gilden