Integrase Inhibitors During Pregnancy: Study Explores Safety and Efficacy

Women living with HIV infection who become pregnant need antiretroviral therapy (ART) not only to protect their own health, but also to prevent the vertical transmission of the virus to their child. But no randomized trials have studied the safety and efficacy of ART regimens containing integrase inhibitors (INIs) compared with those containing non-nucleoside reverse transcriptase inhibitors (NNRTIs) in pregnant women.

To address this lack of data, a group of investigators led by Mark Mirochnick, MD, a professor of pediatrics and chief of the Division of Neonatology at Boston University School of Medicine/Boston Medical Center in Massachusetts, designed a randomized trial comparing an ART regimen containing the INI raltegravir (RAL) with an ART regimen containing the NNRTI efavirenz (EFV) when initiated during pregnancy.

Dr Mirochnick discussed the results of the study on March 5, 2019, at the Conference on Retroviruses and Opportunistic Infections (CROI) 2019 in Seattle, Washington.

The study, NICHD P1081, was a phase IV, multicenter, randomized, open-label trial comparing HIV virologic response to the 2 ART regimens—namely, RAL plus zidovudine and lamivudine, and EFV plus zidovudine and lamivudine. The trial enrolled 408 pregnant women, 206 of whom were in the RAL-ART arm and 202 of whom were in the EFV-ART arm. The study was conducted at 19 sites in Brazil, Argentina, Tanzania, South Africa, Thailand, and the United States.

The primary outcome measures were efficacy based on virologic response as indicated by a plasma HIV level less than 200 copies/mL at delivery; tolerability as indicated by participants’ having remained on the assigned regimen through delivery; and maternal and child safety as indicated by the number of mothers and infants experiencing adverse events greater than or equal to grade 3.

“Both raltegravir and efavirenz were safe and well-tolerated in women initiating ART during pregnancy,” Dr Mirochnick said of the study results. However, he noted that women receiving RAL-ART generally had faster viral load reduction, and that a greater proportion of women receiving RAL-ART had a viral load of less than 200 copies/mL at delivery. He added that “this difference was driven by the women who enrolled (in the study) later in gestation.”

“These data support the use of raltegravir-ART during pregnancy, especially for women starting ART after 28 weeks’ gestation,” Dr Mirochnick concluded.

For more information about Dr Mirochnick’s presentation, click here.

For more CROI 2019 coverage, click here.

—Michael Gerchufsky

Reference:

Mirochnick M, Shapiro DE, Morrison L, et al. Randomized trial of raltegravir-ART vs efavirenz-ART when initiated during pregnancy. Presented at: Conference on Retroviruses and Opportunistic Infections (CROI) 2019; March 5, 2019; Seattle, WA. http://www.croiconference.org/sessions/randomized-trial-raltegravir-art-vs-efavirenz-art-when-initiated-during-pregnancy. Accessed March 7, 2019.