IMPAACT Study on HIV Medications Taken During Pregnancy to Begin New Phase in 2019

An ongoing study funded by the National Institutes of Health (NIH) is investigating how women process medications for HIV and tuberculosis (TB) during pregnancy in an effort to inform treatment guidelines for pregnant and postpartum women.

During pregnancy and in the time soon after, women go through biological changes causing their bodies to process medications differently, meaning standard dosage and safety recommendations may not be ideal for certain drugs. According to a recent news release from the NIH’s National Institute of Allergy and Infectious Diseases (NIAID), since 2003 investigators have studied the pharmacokinetic properties of more than 25 HIV medications in more than 1000 pregnant and postpartum women enrolled in studies in the United States, Africa, Brazil, and Thailand. The study, part of the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Network and currently known as IMPAACT P1026s, has published 27 papers to date and will change its name to IMPAACT P2026s later in 2019.

In an interview with Contagion^®, study investigator Mark H. Mirochnick, MD, explained that women taking HIV and TB medications during pregnancy have done so largely within a vacuum of research. “Pregnant women have been excluded from the drug development programs leading to licensure for HIV medicines. As a result, the safety and pharmacokinetics of HIV drugs have not been studied in pregnant women until after these drugs have received their initial FDA licensure for use in adults and are available for clinical use in the US,” said Dr. Mirochnick, who serves as chief of the Division of Neonatology at Boston University School of Medicine/Boston Medical Center. “The studies necessary for the safe and effective use of these drugs in pregnant women have not been completed until years after these drugs have been approved for use in adults and widely used in pregnant women.”

Since its start, the study has made some key findings and has developed one of world’s largest data sets on HIV and TB medications in pregnancy. For many HIV drugs, such as certain protease inhibitors, the standard adult dose results in lower drug levels in the blood during pregnancy than during the postpartum period and in adults who are not pregnant. As a result, investigators say pregnant women with HIV receiving a higher dose of some protease inhibitors have more beneficial drug levels in their blood. In addition, the study found that postpartum women taking the HIV antiviral drug efavirenz along with the contraceptive etonogestrel have blood levels of etonogestrel that may be too low to prevent pregnancy.

“The most surprising finding of our study is that it has been going on for over 15 years and pregnant women are still excluded from drug development programs leading to drug licensure,” Dr. Mirochnick said. “The problems with exclusion of pregnant women from drug development programs are highlighted by the discovery of the poor drug levels of cobicistat in pregnancy.”

Cobicistat, Dr. Mirochnick explained, is a newer booster intended to block the metabolism and increase the plasma concentrations of other HIV medications, allowing once-a-day dosing for those drugs. Data from IMPAACT P1026s shows that pregnant women receiving cobicistat do not have effective boosting of their HIV medications, leading to lower blood levels of these HIV medicines and decreased effectiveness during pregnancy. As a result of the study, the package inserts for single dose cobicistat and several fixed-dose combination products were modified in 2018 to indicate they should not be used during pregnancy due to low drug exposures.

“We have published the data from our study as each arm has been completed, and these data have been a major source for the pregnancy dosing recommendations for HIV medications made by the US Perinatal HIV Guidelines Committee and by other guidelines groups around the world,” Dr. Mirochnick told Contagion^®. “So long as new HIV and TB medications are being developed and pregnant women are excluded from the drug development process prior to licensure, there will continue to be a need for studies like ours.”