First AIDS

Huge progress has been made in the 25 years of care and treatment of HIV-infected people, and Andrea Kovacs believes that research is at the core.

By Karen Heyman

During the mid-1970s Andrea Kovacs pursued her undergraduate studies at Barnard College in New York City, while at the same time, thousands of gay men across the nation celebrated their sexuality with abandon. After all, the ’60s were over, the disco era was in full hustle and it appeared that there was nothing going around that penicillin could not handle.

By 1980, when Kovacs was a young resident and fellow at the Pediatric Pavilion of Los Angeles County+ University of Southern California Medical Center, she began seeing cases of unusual, perplexing infections. “It was unbelievable,” Kovacs says. “These patients died horrific deaths, unlike anything we’d seen before.”

Four years after the first cases of this deadly disease were reported, researchers confirmed that a virus was the cause of what the Centers for Disease Control and Prevention termed acquired immune deficiency syndrome (AIDS). Dubbed human immunodeficiency virus or HIV, its lethal power came from the ability to destroy T-cells, which fend off infections, including other viruses. HIV was like an army that kills the royal guards then lets foreign invaders sack the palace.

Kovacs, M.D., professor of pediatrics and pathology at the Keck School of Medicine of USC, and head of the division of pediatric infectious diseases at LAC+USC Medical Center, did not expect to be on the frontlines of an illness that was on the front pages of major newspapers. But after a research fellowship in virology in 1984, she knew that AIDS would become the epidemic of her generation.

“Almost overnight I was transformed from being a consultant to being a primary care physician and researcher of a chronic disease that affected whole families,” Kovacs says. “Being involved in the care of these patients, and the research involved in helping them, changed my career goals as well as my life.”

Nevertheless, in the mid-80s, Kovacs and her colleagues never imagined that HIV would reach the pandemic proportions it has today. “Once the first cases of AIDS were reported in women and their babies, and that was 1981 to 1983, it became obvious that this was an infection that could be transmitted from mother to child,” Kovacs recalls. “I came to USC to work on this problem.”

In 1988, she established the Comprehensive Maternal-Child HIV Management and Research Center in the Pediatric Pavilion. “As a mother myself, I knew it was essential to care for the mothers at the same time as their infants and children, since women tend to neglect their own health, but always take care of their children,” she says. Today, the Maternal-Child Center is a publicly and privately funded model for AIDS care, so world-renowned that it was a stop for former Secretary-General of the United Nations Kofi Annan and a U.N. delegation during a visit to Los Angeles in 2003. But at the beginning, it was a shoestring operation, kept going by Kovacs’ determination. “I wrote grants and begged people to help me; we were largely staffed by volunteers,” she remembers.

With research rapidly influencing therapies, Kovacs treated the disease aggressively to buy time and keep patients alive until the next therapy came along. When the HIV drug AZT was not available for children, her clinic staff crushed it and modified the dose for their small patients. When additional drugs became available, Kovacs says they combined them even though there were no pediatric formulations or data.

“The children were dying. We calculated their dosage based on an adult dosage. We crushed the meds and worked with the moms and pharmacists so that the babies and children could get the medication,” she says. Also, before anyone else, Kovacs and her team treated pregnant women for their own health as aggressively as they could. In doing that, they prevented transmission of HIV from mother to child.

Clinic space

After the 1994 Northridge earthquake closed several buildings at the LAC+USC Medical Center, including the Pediatric Pavilion, the Maternal-Child Center shifted to half-a-dozen temporary spaces. Kovacs recalls that the small corner of the AIDS clinic was so crowded that mothers and children had to sit on the floor.

Determined to have a dedicated clinic space, Kovacs appeared before the Los Angeles County AIDS Commission to explain the need for a separate clinic for women and children. She had expected the patients to attend the hearing, but instead found herself testifying alone before the commissioners, most of whom had already expressed that a separate facility was not necessary. Kovacs recalls: “Suddenly, women and children streamed through the doors. It was like The Grapes of Wrath. A hundred of our patients walked in. One little boy started telling his story and everybody started crying. After that, there was no way they wouldn’t get their clinic.”

Model care

From the start, Kovacs realized that the approach to the care and treatment of those infected with HIV had to be different than any other disease treatment seen before. Her patients were disenfranchised, poor minorities with little access to care and virtually no support systems. “I realized it would be essential to provide comprehensive, multi-disciplinary care to the entire family in one setting, while integrating interdisciplinary research from the onset,” she says. Today, the interdisciplinary team is a large group: not just researchers and medical professionals, but social workers and psychologists, legal experts, public health officials and people with expertise in gender, cultural and ethnic studies.

Research core

To have an impact, Kovacs has had to constantly think creatively. Dealing with HIV is a dynamic process that she and her colleagues reassess regularly. Huge progress has been made in 25 years, and Kovacs believes that research is at the core.

“We were the first to discover the association between CD4 [T-cells that help protect the body from infections] counts and the opportunistic infection pneumocystis carinii pneumonia (PCP) in children,” she says. The discovery defined CD4 counts for HIV-infected infants at various stages of disease; in turn this spurred recommendations for prevention of PCP and was used in the development of the first national guidelines for antiretroviral therapy for infants and children with HIV.

Although for years many researchers had attempted to demonstrate that another virus, cytomegalovirus (CMV), affected HIV disease, a 1999 study by Kovacs in the New England Journal of Medicine demonstrated for the first time that CMV accelerated HIV disease progression and encephalopathy in infants and suggested an immune mechanism for this observation.

In her first seven years at USC, Kovacs’ laboratory-based studies focused on understanding perinatal transmission, developing diagnostic tools to identify infected babies, and treating pregnant women to prevent transmission.

“At that time, one third of all babies were infected. We saw one or two infected babies each week,” she recalls.

By 1996, Kovacs had succeeded in preventing transmission in the majority of babies. Kovacs believes medicine’s most important progress in relation to HIV and AIDS has been the almost 100 percent reduction of maternal-to-child transmission in the United States.

“We are lucky here in the U.S. that our patients have access to these medications,” she says. “Unfortunately, that is not true in many parts of the world.” She says that in some areas, medications are not reaching the infected patients, so infants are still becoming infected and dying—as are their mothers. As a result, uninfected babies are orphaned with no one to care for them.

“These are the current issues worldwide and we are committed to helping. Our one-stop approach to care for HIV-infected patients and their affected family members has today, 18 years later, been replicated throughout the country and is the recommended model for HIV care proposed by the World Health Organization and the Joint United Nations Program on AIDS on an international level,” she says. “We know how to do it. We now just need to figure out how to replicate this worldwide.”  

Next generation

In 2001, the clinic dedicated an area to the care of teenagers, expanding its formal name to the Comprehensive Maternal, Child and Adolescent Center for Infectious Disease and Virology at LAC+USC Medical Center. The name change reflected the team’s expanded focus on other infections such as cytomegalovirus, human papilloma virus (HPV) and hepatitis C virus (HCV), as well as vaccine studies for influenza, rotavirus, bacterial infections and HPV.

Adolescent care is especially challenging, says Kovacs. Patients are often compliant as children, only to rebel against treatment when they reach adolescence. The center’s outreach efforts include a youth advisory board of young adults trained to be peer leaders.

“Now that we have, in essence, conquered maternal-to-child transmission in the U.S., we are focusing on preventing infection in our youth. This is one of the highest priorities for me, as they are our future,” she says.

Her research remains focused on interrelated areas: pathogenesis of HIV and associated opportunistic infections and immune mechanisms of containment in women and children; mechanisms of maternal-infant transmission of HIV and co-viral infections; treatment of HIV and other viral infections using novel agents, and treatment strategies for the prevention of transmission.

In addition, along with virologists and immunologists from four national centers, Kovacs is heading a multi-center investigation funded by the National Institutes of Health to continue studies of HCV in co-infected patients.

Her current priorities in HIV research and patient care are the same as the global priorities—to reduce transmission and to treat everyone infected with HIV. There has been progress, she says, such as the development of triple viral therapy that can be taken once daily, which stops HIV replication and allows the immune system to do its job.

“But we still await the vaccine,” she says.

Looking from her office to the busy, comfortable clinic, Kovacs reflects on the progress she has seen since her patients sat on the floor. She looks forward to the next frontier of HIV research, such as the problems of postmenopausal and geriatric patients, something that never could have been imagined a quarter of a century ago.

Kovacs says, “The research is what keeps you going, the promise that you can find some way to make lives better. We know that we can—the very first AIDS baby who was born here, he’s 18. Now that is progress.”

 

"Now that we have, in essence, conquered maternal-to-child transmission in the U.S., we are focusing on preventing infection in our youth. This is one of the highest priorities for me, as they are our future." —Andrea Kovacs

 

 

 

 

Karen Heyman is a freelance writer in Los Angeles. Carol Chaplin contributed to this article.