17P to prevent preterm birth in women with HIV

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Weekly antenatal 17 alpha-hydroxyprogesterone caproate (17P) injections did not reduce the composite risk of preterm delivery or stillbirth among women with HIV in Zambia, according to a placebo-controlled trial.

The study of 800 women living with HIV women found that 9.02% of those randomized to 17P delivered before 37 weeks or had a stillbirth, compared to 8.98% who received placebo.

Study results were presented virtually at the 41st Annual Pregnancy Meeting of the Society for Maternal-Fetal Medicine (SMFM).

“HIV is one of the most common serious medical complications of pregnancy in sub-Saharan Africa, where up to one in four pregnant women are living with HIV,” said Joni Price, MD, MPH, an assistant professor of ob/gyn at the University of North Carolina at Chapel Hill, who served as the study’s investigator of record.

Price said maternal HIV nearly doubles the risk of preterm birth and stillbirth, “even among women who are being treated with modern antiretroviral therapy. Yet we still do not have an effective intervention to reduce this risk.”

Because previous trials have noted 17P can prevent preterm delivery among women with a history of prior spontaneous preterm delivery, the investigators were encouraged that it might also prevent preterm delivery among women whose risk derives from their HIV status.

The study enrolled women recruited from public-sector antenatal clinics in Lusaka, Zambia, over a 2-year period from February 2018 to January 2020.

Participants were randomly allocated to receive weekly intramuscular injections of 250 mg 17P (n = 399) or placebo (n = 401), starting between 16 and 24 gestational weeks and continuing until 37 weeks, delivery or stillbirth, whichever occurred first.

Participants were followed through delivery and postpartum. The final postpartum follow-up visit was completed in August 2020.

The timing of antiretroviral therapy initiation relative to conception did not affect the risk of preterm delivery or stillbirth, nor did it modify the effect of the intervention.

Related adverse events were low and occurred at similar rates between the two study groups.

“We were really hopeful that 17P would be effective because it is a synthetic derivative of the naturally occurring progesterone hormone that can reduce local and systemic inflammation,” Price told Contemporary OB/GYN. “Most evidence points to HIV working through inflammatory mechanisms to incite spontaneous preterm labor and delivery.”

More than surprising, the results are disappointing, according to Price. “We are looking for other possible interventions to reduce the risks of adverse outcomes in this high-risk population,” she said. “Meanwhile, we take solace that our study population had an overall low risk of preterm delivery and stillbirth.”

The investigators are evaluating whether this low risk was due to strict study eligibility criteria; for instance, women with prior spontaneous preterm delivery were excluded. Low risk might also be attributable to some other participant characteristics or trial procedures.

Still, there was a reduction in risk of infants born very small for gestational age, a promising finding that Price and her colleagues will investigate in future studies.

The very low incidence of infant HIV was also equivalent between women receiving 17P and placebo. “It is reassuring that 17P can be used in women with HIV without increasing the risk of vertical transmission,” Price said.

The authors are pursuing funding to test oral anti-inflammatory medications and nutritional supplements to reduce the risk of preterm delivery among women with HIV in Zambia. “We are also undertaking analyses of the vaginal microbiome and inflammation to better understand whether the mechanisms underlying HIV-related preterm delivery may be detected in the local microenvironment and potentially modifiable through probiotic or other biotherapeutic formulations,” Price said.

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Price reports no relevant disclosures.