Dolutegravir During Pregnancy Appears Safe

By Will Boggs MD

April 23, 2019

NEW YORK (Reuters Health) - Dolutegravir treatment does not appear to worsen pregnancy or neonatal outcomes, according to a registry study.

"While the results are not conclusive because of the small number of pregnancies, neither Antiretroviral Pregnancy Registry (APR) nor European Pregnancy and Pediatric HIV Cohort Collaboration (EPPICC) showed increased risk for neural tube defects (NTDs) or other adverse pregnancy or neonatal outcomes following prenatal use of dolutegravir," Dr. Vani Vannappagari from ViiV Healthcare, Research Triangle Park, and the University of North Carolina at Chapel Hill told Reuters Health by email.

Dolutegravir is an integrase strand transfer inhibitor used in the treatment of HIV-1 infection in adults and children over age 6 as part of combination antiretroviral therapy.

Pregnancy was an exclusion criterion in all phase 3 dolutegravir trials, but a potential safety signal was identified in a Botswana study, with four cases of NTDs reported among infants born to 426 women who conceived while receiving dolutegravir-based regimens.

Dr. Vannappagari and Dr. Claire Thorne from UCL Great Ormond Street Institute of Child Health, in London, used prospective data from APR and EPPICC to assess fetal and neonatal outcomes following maternal dolutegravir use during pregnancy.

Among the 265 pregnancies included in APR, there were 246 (92.8%) live births (nine twins), six (2.3%) induced abortions, 11 (4.2%) spontaneous abortions, and two (0.8%) stillbirths.

Birth defects occurred in seven of 255 live-born neonates (2.7%), including five of 162 (3.1%) with exposure at conception or during the first trimester, the researchers report in the Journal of Acquired Immune Deficiency Syndrome, online March 29.

Of 84 pregnancies with outcomes reported to EPPICC, there were 81 live births, one stillbirth, one induced abortion and one spontaneous abortion. Birth defects occurred in 4 of 81 (4.9%) live and stillborn neonates.

There were no NTDs or central nervous system defects reported in either registry.

"These findings may provide some reassurance to women whose pregnancies have already been exposed to dolutegravir or who have limited therapeutic options," the researchers conclude.

"HIV-positive women of childbearing potential, pregnant women, and their health care professionals should follow recommendations on dolutegravir use," Dr. Vannappagari said. "A careful consideration of all treatment options and contraceptive needs, as appropriate, should be presented and discussed with the women."

Christine Hughes of the University of Alberta Faculty of Pharmacy and Pharmaceutical Sciences, in Edmonton, Canada, who recently reviewed the safety of dolutegravir in pregnant women, told Reuters Health by email, "There was no safety signal based on outcomes evaluated in these two data sets, and importantly no reports of neural tube defects. While this data is reassuring for women who become pregnant while taking dolutegravir or perhaps require dolutegravir based on limited options, the authors acknowledge in the limitations that there were not enough first trimester exposures to estimate overall prevalence of birth defects."

"I think these findings can supplement the recommended points to highlight when discussing the risks and benefits of continuing dolutegravir, as outlined by the Department of Health and Human Services (HHS) perinatal guidelines," said Dr. Hughes, who was not involved in the new work.

She added, "Clinicians should report antiretroviral use in pregnancy to the APR (or similar registry) to learn more about safety of all antiretrovirals in pregnancy."

The most recent dolutegravir (Tivicay) label includes this warning: "Embryo-fetal toxicity may occur when used at the time of conception and in early pregnancy. Avoid use of Tivicay at the time of conception through the first trimester of pregnancy due to the risk of neural tube defects. Advise adolescents and adults of childbearing potential to use effective contraception."

The label also says: "Avoid use of Tivicay at the time of conception through the first trimester due to the risk of neural tube defects. Pregnancy testing and contraception are recommended in adolescents and adults of childbearing potential."

It includes information for patient counseling and is available at https://bit.ly/2v4FiFa.

ViiV Healthcare, which sells Tivicay, funded the study and provided grants and personal fees to Dr. Thorne.

SOURCE: https://bit.ly/2XfZjoj

J Acquir Immune Defic Syndr 2019.

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