Principal Investigator Focus: Dr. Lisa Frenkel

Dr. Lisa Frenkel: Preventing Mother–Infant HIV Transmission Around the Globe

Lisa Frenkel

As a clinician and researcher specializing in human immunodeficiency virus (HIV), Dr. Lisa Frenkel, an investigator in the Center for Global Infectious Disease Research, stands at the crossroads between two worlds. The first is the U.S., where education and treatment have virtually eliminated pediatric HIV. The second is the developing world, where around 400,000 children will be born with the disease this year. Frenkel’s research aims to bridge these worlds by finding practical ways to prevent mother-infant HIV transmission, particularly in resource-strapped communities.

“I’d like to get to the point where we can apply the U.S. approach elsewhere, but in a more affordable way,” she said.

“If we prove our hypothesis, it could be an important step towards treatments to reduce HIV transmission from mothers to their infants.”

Preventing drug-resistant HIV

One of Frenkel’s main projects has been aimed at preventing drug-resistant HIV. In the U.S. and Europe, pregnant, HIV-infected women are usually treated with antiretroviral therapy (ART); the “cocktail” is a combination of drugs that makes selection of drug resistance less likely. These women are also routinely tested for drug-resistant strains before starting ART and, if resistant strains are present, treated with drugs that target them.

In low-resource countries, drug-resistant HIV is on the rise, in part because HIV-infected mothers and their infants are often treated with just one dose of a drug called nevirapine. While this is relatively inexpensive, it promotes drug resistance.

Further complicating matters, testing for drug-resistant HIV strains is expensive, often costing $500 per patient in the U.S. As a solution, Frenkel’s team developed a test that uses only about $3 for the supplies per patient, plus technician time. Frenkel is working to make the test widely available in some African countries with hopes it will help local doctors provide appropriate treatments and better allocate scarce resources.

“If a baby is not infected with resistant virus, lower-cost ART, that includes nevirapine, can be used for treatment, whereas a different treatment that is more expensive must be used if the baby has resistant virus,” Frenkel said.

Investigating how HIV is transmitted to infants

Frenkel is also working to understand how HIV is transmitted via breast milk. This is one of the main sources of mother-infant transmission in low-resource countries, where mothers usually can’t switch to formula due to its high cost and the lack of clean water.

Frenkel is testing whether treating infants with ART while breastfeeding can immunize the baby to their mother’s HIV. The researchers have also investigated the causes of mastitis, or breast inflammation, which increase HIV levels in breast milk, thereby increasing the risk of transmission.

Frenkel’s latest research builds on the finding to investigate another key HIV puzzle. Even when ARTs suppress the disease in patients’ bloodstreams, about 10% to 15% of those patients still shed the virus from their rectums or genital tracts.

This means they can still transmit the disease. While some researchers hypothesize that low drug levels allow viral replication at these sites, Frenkel suspects inflammation may drive this discordant relationship. By causing white blood cells – which contain HIV deoxyribonucleic acid – to multiply at a faster rate, Frenkel believes inflammation might increase quantities of HIV in the area and thereby increase the amount of HIV that is shed in genital and rectal secretions.

Frenkel is conducting a study in Peru to test this hypothesis. If it is viral replication that is occurring in the genital tract, then therapies to inhibit it would be needed. However, if it is due to inflammation, then it might be possible to slow HIV transmission by targeted therapies to lessen the specific inflammatory pathway.

Thus, “If we prove our hypothesis, it could be an important step towards treatments to reduce HIV transmission between sexual partners and from mothers to their infants during the child’s birth,” Frenkel said.