Why does it take so long to gather antiretroviral drug safety data for pregnant people with HIV in the US?

Lengthy delays between drug approval and accumulation of pregnancy safety data in the U.S. could endanger infants whose birth parents are living with HIV, according to a recently published data analysis. Better reporting to the Antiretroviral Pregnancy Registry is needed to speed up data collection, the researchers urge.

About This Study

“Safety Data Timelines for Pregnant Individuals with HIV on Antiretroviral Therapy” was published online on May 6, 2024, in Clinical Infectious Diseases. The lead author is William R. Short, M.D., M.P.H., of the Division of Infectious Diseases at Perelman School of Medicine of the University of Pennsylvania in Philadelphia.

Key Research Findings

The focus of this study was to calculate the delay between an antiretroviral drug’s approval by the U.S. Food and Drug Administration and the accumulation of sufficient data for evaluating its safety for infants born to people taking the drug. More than 200 first-trimester exposures must have been reported to the Antiretroviral Pregnancy Registry for a primary analysis comparing birth defect rates between early and late pregnancy exposure. Health care providers may, but are not required to, report to the registry.

The registry began in 1989. Study data came from the registry’s July 2023 interim report when 22 antiretroviral drugs, plus zidovudine and lamivudine, had met the primary analysis threshold. (Zidovudine and lamivudine were excluded because their safety had been analyzed when the registry assessed only classes of drugs, not individual medications.) The median delay between drug approval and primary analysis was six years.

To enable detection of at least a 1.5-fold increase in birth defects, a minimum of 1,000 first-trimester exposures must be reported. That threshold was met by 10 drugs plus the two early antiretrovirals after an average of 12.5 years from drug approval. For the detection of rare defects, which occur in less than one in 1000 infants, a sample size of 2,000 is needed. In this category, a median time of inclusion was 13 years.

Discussion Highlights and Implications for Practice

Many women with HIV of childbearing age have unplanned pregnancies, the researchers pointed out. The delay between drug approval and evaluation of safety during pregnancy means that newer antiretrovirals, as well as medications for people with limited HIV treatment options, are prescribed and taken without knowing how they may affect a developing fetus. Limited reporting to the Antiretroviral Pregnancy Registry is partly to blame for these delays, they said.

The authors commented that outreach efforts to physicians and other HIV providers through professional associations and/or mandatory reporting could accelerate data collection to speed up assessment of pregnancy safety. They also suggested that more education and training, as well as providing incentives to providers, may encourage participation in the registry.

By Barbara Jungwirth