19. Experts in Focus: Dr. Lynne Mofenson

When Lynne Mofenson, M.D., first joined the National Institutes of Health (NIH) in 1989, the AIDS epidemic was in full force. After four and a half years of working at the Massachusetts Department of Public Health as Assistant Commissioner, Division of Communicable Disease Control, focusing on infectious diseases, including HIV, she joined NIH to work specifically on fighting pediatric HIV and efforts to prevent mother-to-child transmission.

“Even back then we knew that mothers living with HIV were passing the virus onto their babies, but we didn’t know how to prevent it. What we did know was that mother-to-child transmission of HIV was frequent, and it was fatal. And we knew that we had to do something to stop it,” said Dr. Mofenson.

Her team at the Eunice Kennedy Shriver National Institute for Child Health and Human Development (NICHD) joined forces with the team at the National Institute of Allergies and Infectious Diseases (NIAID) to develop a clinical trial that tested the use of a new antiretroviral drug called AZT in pregnant women living with HIV to see if it could reduce the rate of transmission from mother to baby. While AZT is well-known today, at that time it was only approved for use in non-pregnant adults.

“Back then there were lots of unknowns. We weren’t even sure that giving AZT to a mother would prevent her from the passing the virus on to her baby,  and we didn’t know when we should give the medicine to the women — during her entire pregnancy or right before childbirth. But we knew we had to try something, anything, to curb this epidemic,” explained Dr. Mofenson.

In fact, AZT was a controversial drug in the early 1990s. It was considered highly toxic and many infectious disease experts were against the trial for fear it would harm the babies more than it would help them. But something had to be done to stop children from contracting HIV, and it had to be done quickly.

Combating Fear and Stigma

“HIV was a big secret, especially for children infected with the virus, mostly because there was no treatment. HIV was essentially a death sentence and everyone was afraid of catching it.

“People didn’t understand how the virus was transmitted. They were afraid for their children to even drink out of the same water fountain as a child who was HIV-positive, let alone attend school or daycare with them,” remembered Dr. Mofenson.

And this same stigma was a key challenge to getting the trial up and running.  

“There was a lot of backlash; trial researchers had to change their home phone numbers because of the threatening calls they would get. Many people really believed we were going to poison these babies.”

But Dr. Mofenson and her colleagues persisted and started the AIDS Clinical Trials Group (ACTG) Protocol 076 trial in April 1991.

“We knew we had just this one chance to make our trial work. We started administering AZT to HIV-positive women during pregnancy (after the first trimester), during labor, and we gave it to newborns for 6 weeks starting shortly after birth.

“We were targeting all the transmission possibilities at once and giving the drug to the baby for additional protection. It was a ‘kitchen sink’ approach, targeting all potential times of transmission to maximize the chance the intervention would prevent transmission.”

And after less than three years, the results of the trial were staggering. An independent review board found that transmission rates were reduced by nearly 70%  — proving unequivocally that by giving antiretroviral therapy (ART) to a woman during pregnancy and childbirth, the risk of her child contracting HIV was greatly reduced.

“We were all thrilled and astounded, we thought our method might work, but we had no idea it was going to work as well as it did.”

Dr. Mofenson and her team moved quickly to implement recommendations for broad use of AZT as a prevention of mother-to-child transmission of HIV (PMTCT) method. Dr. Mofenson chaired the Public Health Service Task Force charged with implementing the trial results. Within two months, initial guidance for health providers was issued and in less than a year after the clinical trial results, the FDA approved AZT for PMTCT and the practice was being widely used across the United States.

“It was a true success story for everyone involved, including the Elizabeth Glaser Pediatric AIDS Foundation (EGPAF). Elizabeth Glaser was a strong advocate for getting medications to mothers and children living with HIV at that time. Her voice was vital to getting the funding and attention we needed to fight pediatric HIV.”

Making Progress

Once treatment and prevention measures became more widely available, some of the fear associated with HIV subsided. People were no longer dying and more people were learning about the ways HIV could be — and more importantly, could not be — contracted.

AZT was finally made available to treat children who were living with HIV. With funding available for pediatric clinical trials – in part due to Elizabeth Glaser’s advocacy — new drugs became available for treatment of children, and combination ART became standard for treatment of both children and adults. With these advances, fewer children were dying and fewer children were contracting the virus.

“It was really the beginning of the fulfillment of Elizabeth Glaser’s vision to see a world where no child has AIDS. I think Elizabeth’s son, Jake, is a great example of the success we saw getting treatment to children in the early- and mid-1990s. Thanks to his mother’s hard work and the availability of potent treatment for children, Jake was able to grow up into a healthy young man and carry on in his mother’s footsteps.

“It’s very rewarding to look back and see that we persevered through this battle thanks to the hard work of the scientists funded by NIH and advocates like Elizabeth Glaser.”

Fighting the Epidemic Abroad

However, while great progress was being made in the United States, the AIDS epidemic was still raging in sub-Saharan Africa. The challenge was applying what researchers and doctors had learned in the United States to countries in Africa where health systems and infrastructure were very weak.  

“We faced many challenges, one of the biggest ones being breastfeeding. We knew how to prevent the virus from spreading in utero and during birth, but in Africa, due to the importance of breastfeeding for overall child survival in countries where infectious diseases are a major cause of infant death and affordable and safe infant formula is not available due to limited resources, we had to shift our focus to preventing postpartum (breastfeeding) transmission.”

By the early 2000s, researchers conducted clinical trials that were able to prove that if a women remained on ART while breastfeeding, she could keep her baby safe from contracting HIV through breast milk.

“The ability of HIV-positive women to breastfeed their babies was another tremendous success story in the fight against AIDS in Africa. That finding in conjunction with implementation of the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR) was what really helped turn the tide of the pediatric HIV epidemic in Africa,” said Dr. Mofenson.

Dreaming of an AIDS-free Future

“Starting from my internship days, everything moved around HIV and children for me. In fact, my involvement with AIDS started before the disease even had a name.”

Dr. Mofenson was an intern at Boston Children’s Hospital in 1977 and one of her very first patients was a 6-month old boy born to parents who were intravenous drug users. The boy was malnourished and had multiple infections and immunodeficiency problems — including low CD4 cells, then called “e-rosette” cells. During his six weeks in the hospital, Dr. Mofenson and her colleagues struggled to treat unusual infections in the little boy and to understand why he had this strange, unexplained immune deficiency. Eventually the little boy died due to an uncommon fungal infection in his brain.

“The feeling of sadness that I couldn’t help this little boy stayed with me through my career. And looking back, I strongly suspect he was HIV-positive. He had all the symptoms that we now attribute to pediatric HIV.”

From that time forward, Dr. Mofenson has been dedicated to treating and preventing HIV in children. And even today, her work at EGPAF focuses on ensuring that children around the world are able to live healthy lives.

“The 3.2 million children who are living with HIV right now, those children ARE the AIDS-free future. Our next challenge is ensuring that we have the health care infrastructure and systems in place to get these kids the medicines they need to live healthy lives and ensure they don’t pass the virus onto others. Treating these children is key to creating a world where no child has AIDS.”