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Doctors Across Borders

Since a UCLA physician first identified the disease that would become known as AIDS nearly 30 years ago, doctors here have been at the forefront of the fight against the virus. Today, they battle the HIV/AIDS epidemic on local and global fronts - whether it is in an African community, a favela in Brazil or on the streets of Los Angeles. - By Dan Gordon

There aren’t words sufficient to describe the devastation that HIV/AIDS has wreaked in sub-Saharan Africa – 22-million people live with the disease and the epidemic kills about 1.5-million people each year and has orphaned nearly 12-million children. But even within that beleaguered region, the small, landlocked country of Malawi is particularly tormented.

In this densely populated nation of nearly 14-million people, where an estimated one-in-eight is infected and the typical family lives on less than $200 a year, the sparse healthcare infrastructure is stretched beyond its limited capacity. Malawi has only about one physician for every 100,000 patients, and they are fighting not just HIV/AIDS but the complicating effects of rampant malnutrition, malaria and diarrheal diseases. As if all of that weren’t enough, the social stigma associated with HIV/AIDS is so great that much of the population is reluctant to get tested or, if they do know, to disclose their HIV-positive status or seek potentially lifesaving treatment, assuming that it’s even available.

But where some might look at the conditions in Malawi and see only insurmountable obstacles, a group of David Geffen School of Medicine at UCLA faculty, trainees and alumni see opportunities. “Anything we do there has incredible benefit,” says Thomas J. Coates, Ph.D., the Michael and Sue Steinberg Endowed Professor of Global AIDS Research in the Division of Infectious Diseases and director of the UCLA Program in Global Health, which has mounted a sustained effort to assist the impoverished nation’s fight against the epidemic. “I’ve been working on and off with HIV/AIDS since 1982, and the only thing that keeps me going is hope. The sheer crush of the epidemic, especially in sub-Saharan Africa, can be overwhelming. But accomplishing even small things can make a huge difference.”

Dr. Coates is directing a broad-based effort in the southeastern African country that has helped to strengthen an HIV/AIDS clinic at Partners in Hope Medical Center in the capital city of Lilongwe by establishing a research laboratory there and sending more than a dozen UCLA internal-medicine residents for elective rotations to treat patients in the clinic. (For every two residents that UCLA sends, the Department of Medicine also provides funds to train a Malawian clinical officer alongside the UCLA residents.)

He and his UCLA colleagues have collaborated with groups both at home and in Malawi, including the Los Angeles-based nonprofit Partners in Malawi, which raised more than $1 million to establish the clinic. It also supports the work of former UCLA family-practice resident Perry Jansen, M.D., who moved to Malawi with his family seven years ago to care full-time for people with HIV, and John Hamilton, former assistant provost for UCLA, who now works in Malawi supporting the activities of the Program in Global Health.

Ten-thousand miles from malawi, Gail Wyatt, Ph.D., is in a similar fight on another front. Dr. Wyatt is associate director of the UCLA AIDS Institute, and for more than a decade, she has led a team of researchers who work to engage underserved and difficult-to-reach populations in studies that might benefit them. Since the early days of the epidemic, she has focused her efforts on examining the psychosocial factors that increase a person’s risk of HIV infection.

Dr. Wyatt has, for example, reported that one-in-two women with HIV and one-in-four men have a history of childhood sexual abuse, and she and her colleagues have developed interventions designed to help these men and women address the psychological issues caused by the abuse and make healthier choices about their sexual behavior and self-protection. An intervention she developed for HIV-positive women with histories of childhood sexual abuse, currently being disseminated in the State of New York, focuses on the post-traumatic stress, depression and sexual trauma that many women experience as a result of their abuse. “It is helping women to disentangle things for which they were not responsible and take control and responsibility for their own sexuality today,” she says. And Dr. Wyatt heads the Los Angeles site of the Eban HIV/STD Risk Reduction Intervention, a multi-site program for African-American couples who are serodiscordant (one positive, one negative). “Information about HIV prevention is typically given to individuals,” Dr. Wyatt explains. “This is a chance to educate couples.”

In addition to the work she does in the U.S., Dr. Wyatt is involved in capacity-building overseas. In collaboration with five South African universities, she heads a program to train academicians in that country to conduct research on trauma and mental health, much of it related to HIV/AIDS. The program brings the trainees to UCLA for three months of study and provides mentorship when they return to South Africa. There also are yearly workshops to train additional South Africans. The program has created a network of universities that will work with UCLA in the future on multi-site studies of trauma-related issues connected to HIV risk.

But with all of the emphasis on international efforts, Dr. Wyatt is concerned there is a lack of focus on HIV/AIDS at home, where, she says, “we have a national crisis.” While she acknowledges that the U.S. Centers for Disease Control and Prevention has moreaggressively addressed such concerns as the number of African Americans who are not being tested and don’t know they are HIVinfected, Dr. Wyatt laments: “We are not doing an adequate job of making people aware that this infection is still spreading among some populations here in the United States, and we have no national policy for HIV prevention.”

Drs. Coates and Wyatt are but two of the many UCLA physicians and researchers who are engaged in the fight against HIV/AIDS on both local and global fronts through prevention, counseling, treatment, policy and building the capacity of communities to handle the epidemic. It is a daunting challenge: According to the most-recent statistics from UNAIDS, an estimated 33-million people worldwide – 1.2 million in the U.S. – are infected with HIV, and between 2.2-million and 3.2-million new cases are diagnosed annually. “Three-million new infections in a year translates into 8,200 infections a day or 342 infections in an hour,” Dr. Coates notes. “Given that HIV is lethal in about 99 percent of the people it infects if left untreated, that is roughly the equivalent of a Boeing 747 crashing every hour of every day for a year.”

The members of the UCLA Center for Clinical AIDS Research and Education (CARE Center) are among others on campus also in the fight, operating a medical office in West Los Angeles that integrates education, research and primary care by appointment for patients with HIV/AIDS. Judith Currier, M.D., associate director of the CARE Center, and Raphael Landovitz, M.D., a CARE Center physician, are leading a major effort in Los Angeles County to make post-exposure HIV prophylaxis (PEP) available after a high-risk encounter. Although there is limited data on the efficacy of using antiretroviral therapy after potential exposure, the data that are available suggest an 80-percent reduction in the chance of HIV infection for those who comply with a 28-day course of treatment, starting within 72 hours of the high-risk exposure.

Arriving in Los Angeles in 2006 after completing his training at Harvard, Dr. Landovitz was surprised to find that, despite both national and state guidelines endorsing the use of the technology, there was limited knowledge about and use of PEP, particularly in low-income and minority communities where the epidemic is growing the fastest. He and Dr. Currier joined with other academics, Los Angeles city- and county-government and public-health officials and community representatives to convene a series of roundtable discussions on how best to employ PEP as a prevention strategy in the county. The discussions have resulted in a pilot program, headed by Dr. Landovitz and funded by the Los Angeles County Office of AIDS Programs and Policy, to provide post-exposure prophylaxis treatment at no cost to participants at two sites with large populations of HIV-infected and at-risk patients: the Los Angeles Gay and Lesbian Center and the Oasis Clinic in South Los Angeles.

Nearly three decades after a UCLA physician first published a description of the new disease, the shame attached to HIV/AIDS continues to be a major problem. Often, it can be powerful enough to keep people from seeking vital HIV-related services. In Los Angeles and in six foreign countries – South Africa, Uganda, Australia, Thailand, India and China – Mary Jane Rotheram-Borus, Ph.D., and an interdisciplinary team of collaborators designs, implements and evaluates intervention programs that aim to overcome the stigma by integrating HIV prevention and treatment into comprehensive family-wellness programs that utilize a community’s natural social networks to extend beyond traditional healthcare settings.

“Programs that are HIV-only can be highly stigmatized,” says Dr. Rotheram-Borus, director of the federally funded Center for HIV Identification, Prevention and Treatment Services at UCLA. “But whether the concern is HIV, obesity, smoking, alcohol or heart disease, all of evidence-based medicine shares core components and processes that can be applied to helping people maintain their health.” In the developing world, where the strain of HIV is particularly pronounced, this integration strategy brings the added advantage of greater efficiency. “The healthcare budgets of the majority of the African countries allocate less than $30 per individual per year,” Dr. Rotheram-Boras says. “If HIV services are delivered separately, at HIV clinics, there is both the problem of stigma and the potential for draining resources from other important health issues.”

To make her wellness programs accessible, Dr. Rotheram-Borus locates them in everyday community settings such as churches, local bodegas and shopping malls – a family-wellness center is scheduled to open adjacent to Santa Monica’s Third Street Promenade in September – and integrates HIV services with other health concerns facing the community. She also taps families who are thriving within each community to serve as role models. “Regardless of community poverty, there always are families that are pragmatic problem solvers. Local peer role models are valuable assets in assisting with intervention,” she explains.

Leadership training is a key focus of Dr. Coates’s efforts. “The investment of the U.S. government has been enormous, and we are bringing scientific advances to the developing world,” he says. “But to make it work, there need to be people who have the time, commitment, resources and, ultimately, the training to build a local response.” That, says Dr. Coates, is why partnerships are so important. “Our goal is to bolster our local partners so that when we step away, they can move into the leadership positions.”

Arox Kamng’ona, a Malawian who earned his master’s degree in molecular and cell biology at the University of Cape Town in South Africa and is currently a lecturer at the University of Malawi College of Medicine (COM), hopes to obtain a Ph.D. through the COM and UCLA and then assume a leadership role in the Partners in Hope laboratory. Kamng’ona is teaming with Otto Yang, M.D., a UCLA associate professor in the Division of Infectious Diseases who is working to help build the infrastructure for both clinical and research programs in Malawi. Their project to better define the strains of HIV that are circulating in Malawi is to be conducted in Malawi and at UCLA.

“The Malawi government recognizes the need to increase the number of trained professionals in clinical fields,” Kamng’ona says. “This pilot project will help to establish the infrastructure to support my advanced training. It will empower me with HIV immuno-virology research skills for the betterment of the patient population in Malawi.” Training Malawians like Kamng’ona to be principal investigators “is very important for the country,” notes Risa Hoffman, M.D. ’00, clinical instructor in the Division of Infectious Diseases. At the moment, however, “most of the research that comes out of Malawi is by Americans who live and work there.”

Dr. Hoffman represents the other side of the equation – the ability of Dr. Coates’s program to attract American physicians and scientists to the cause. After completing fellowship research in Malawi under the mentorship of Drs. Coates and Yang, she chose to stay on faculty in the Program in Global Health, dedicated to biomedical HIV prevention and supporting medical education in Malawi and Mozambique.

The current centerpiece of the capacity-building effort in Malawi is a program with Chancellor College in the city of Zomba. The liberal-arts and professional school trains the men and women who will be Malawi’s future business and political leaders. In a society in which the stigma of HIV/AIDS is considerable, the inclination to talk about sexual issues minimal and the level of gender inequality significant, the UCLA group has collaborated with the college on a series of programs to bring Malawian and American students and teachers together to explore issues of HIV/AIDS and the ways in which the epidemic is being fueled in Malawi. The goal is to enlighten the next generation of leaders about HIV – and to ensure that they don’t fall prey to the virus themselves.

“This program has changed the dialogue about HIV within the Chancellor College community,” says Dr. Coates. “It’s too early to tell if we’re having any effect on the rates of HIV among the college students, or what they’re going to do when they go on to their careers, but clearly we have had an impact on how they’re thinking about HIV.”

Malawi is not the only country on which the Program in Global Health focuses its attention. There also are initiatives in South Africa, Uganda, Zimbabwe, Tanzania, China, Thailand and Peru. For example, Dr. Coates heads a 48-community randomized clinical trial in South Africa, Zimbabwe, Tanzania and Thailand that is examining the impact of community-wide testing – enlisting more than half of the population of a community to be routinely tested and counseled – as a way to cut through the shame that prevents people in many developing countries from being tested and/or treated. In South Africa, where 17 percent of the world’s HIV-positive population resides, obstructive government policies have often stood in the way; there, Dr. Coates and colleagues have focused on policy-related work such as an effort to change the South African law that requires HIV testing be done by a nurse, a constraint that limits testing and keeps many in the dark about their HIV status.

When the HI V/AIDS epidemic began, Yvonne Bryson, M.D., was present at the clinical epicenter. A virologist and pediatrician, she was brought in by Michael Gottlieb, M.D., to see “Patient Zero,” the man who became the first identified case of the disease that would be known as AIDS, in 1981. Before long, Dr. Bryson began seeing children who were sick, some of them dying, from causes that couldn’t be determined. Soon it was apparent that HIV was being transmitted from blood transfusions and from pregnant mothers to their infants. “One-in-four babies born to HIV-positive mothers was infected,” Dr. Bryson recalls. “I had to break the news to these mothers, and I would be in tears.”

Dr. Bryson already ran a successful laboratory that would contribute critical insights into how the mother-infant transmission occurs and how to reduce the risk and provide early diagnosis of infants. But she wanted to do more. She led an effort that established the Los Angeles Pediatric AIDS Consortium and Care 4 Families. It comprises collaborative, one-stop centers throughout Los Angeles for disenfranchised pregnant women and their children, offering comprehensive services that include case-management social work, peer counseling and support groups, along with state-of-the-care treatment. (Jaime Deville, M.D., associate professor of pediatric infectious diseases, is the clinical director for the CARE 4 Families clinic at the David Geffen School of Medicine at UCLA and Mattel Children’s Hospital UCLA, where more than 70 families are followed.)

Later, Dr. Bryson, with the help of Karin Nielsen, M.D., UCLA associate clinical professor of pediatric infectious diseases, helped to take the model overseas, organizing and training personnel to run similar centers in Brazil and parts of Africa, as well as implementing strategies for encouraging rapid testing and counseling. And in 1988, Dr. Bryson and E. Richard Stiehm, M.D., UCLA profesprofessor of pediatric immunology, were involved in establishing the Elizabeth Glaser Pediatric AIDS Foundation, which would become the nation’s largest fundraiser for pediatric-AIDS research.

In the mid-1990s came the breakthrough: Dr. Bryson was one of the first investigators to study Zidovudine AZT, a drug that was found to dramatically reduce mother-to-infant HIV transmission – from 25 percent to less than 8 percent for mothers who receive treatment. That finding led to routine HIV testing of pregnant women in the United States, which ultimately reduced motherto- child transmission to very-low levels. This result provided the proof of concept for the investigation of other new drugs, and it also led to Dr. Bryson’s involvement in bringing technology and scientific advances globally to resource-poor populations. For example, the global National Institutes of Health IMPAACT (International Maternal Pediatric Adolescent AIDS Clinical Trials) network to prevent mother-child transmission, of which she is the scientific chair, is involved in 67 different clinical sites in such countries as Africa, India, Thailand and South America.

Many of the children Dr. Bryson saw as patients in the early years of the epidemic are now in their teens and beyond, and several have had babies of their own. And with the advent of new drugs and antiretroviral treatments that have turned what used to be a death sentence into a treatable chronic illness, “the whole outlook has changed,” Dr. Bryson says. “It’s extremely gratifying.” But there still are frustrations. “The advances are only as good as the next person you identify, educate and treat, and some are still falling through the cracks,” she says. “It’s very important that we not become complacent just because we have been successful. There is still much to do.”

As the 21st century dawned and the global pandemic turned 20, complacency wasn’t the issue; hopelessness was. New infections were at all-time highs. Only 4 percent of patients in developing countries had access to life-extending antiretroviral treatment. Even in the West, only one-third of those who were infected were receiving the drugs.

In June 2001, the first United Nations General Assembly Special Session ever convened to discuss a health issue was held in New York. At the end of the session, all 189 countries adopted the “Declaration of Commitment on HIV/AIDS,” a call to action that has served as a driving force in the global response ever since. In early 2003, the United States, through the President’s Emergency Plan for AIDS Relief (PEPFAR), committed $15 billion over five years to combat HIV/AIDS in 120 countries. PEPFAR increased the number of people in sub-Saharan Africa who would receive antiretroviral treatment by more than tenfold; powerful advances have also resulted from programs supported by the Global Fund.

“We are light years ahead of where we were in 2001,” says Dr. Coates. “People were saying that the United Nations document was pie-in-the-sky, that it couldn’t be achieved. Now, 30 percent of the people who need to be on antiretroviral therapy worldwide are receiving the therapy. A country as poor as Malawi has half the population who need treatment receiving it, and is experiencing a decline in deaths due to AIDS. The investment is paying off.”

But the struggle is far from over. If 30 percent of the world’s 33-million HIV/AIDS patients are receiving lifesaving treatment, it means 23 million of them are not. At the current rate of infection, five people contract the virus for every two who are started on treatment. Although there are many prevention-success stories, Dr. Coates points out that efforts continue to be obstructed in many countries by bans on funding for syringe exchanges and moralistic discourse that creeps into the public-health discussion of sexuality.

Indeed, to Dr. Coates and his UCLA colleagues who are working to combat HIV/AIDS both locally and in the developing world, success has led to a new concern. “With all of the progress that’s been made, it’s easy for leaders to think, ‘We’ve done that, let’s move on to the next issue,’ especially during economic hard times,” Dr. Coates says. “We have had a good start, but it’s just a start. Our big challenge now is maintaining the momentum.”

Dan Gordon writes extensively about medical issues and is a regular contributor to UCLA Medicine.





Photography by Riccardo Gangale/AP Images



 





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