NIH to Evaluate HIV Drug Safety in Pregnant Women

Data are limited regarding the safety and efficacy of antiretroviral therapy in pregnant women.

The National Institutes of Health (NIH) recently launched a large clinical trial that will investigate the safety and efficacy of 3 antiretroviral therapy (ART) regimens among pregnant women with HIV and how it may affect their infants, according to a press release.

Researchers will evaluate the safety of the first-line HIV therapy recommended by the World Health Organization (WHO), along with 2 newer antiretroviral regimens.

The goal of the new study is to increase knowledge regarding the use of the new drugs during pregnancy in hopes of ensuring HIV-positive mothers and their infants receive proper care, according to the release.

The NIH said that 1.5 million HIV-positive women have children each year. Previous studies have confirmed that ART suppresses HIV and prevents mother-to-child transmission.

In the new study, the investigators plan to assess the virologic efficacy of the treatments by examining the mother’s viral load at the time of delivery. They also plan to evaluate how the regimens impact rates of preterm delivery, low infant birth rates, maternal adverse events, and infant adverse events, according to the release.

The NIH noted that the first patients have begun ART treatment in Zimbabwe.

“Women should have access to the best available HIV medications throughout their lives,” said Anthony S. Fauci, MD, director of National Institute of Allergy and Infectious Diseases. “Our priority is to evaluate newer, improved antiretroviral drugs during pregnancy to identify the optimal regimens for women living with HIV and their infants.”

WHO recommends that pregnant women with HIV receive ART with efavirenz (EFV), lamivudine (3TC) or emtricitabine (FTC), and tenofovir disoproxil fumarate (TDF).

However, the NIH said this regimen is not appropriate for all patients. EFV has been linked to neuropsychiatric symptoms, TDF can cause kidney problems and loss of bone mineral density, and prenatal exposure to TDF may result in bone loss in infants, according to the NIH.

The researchers will compare EFV/FTC/TDF regimens against those that contain dolutegravir (DTG) plus tenofovir alafenamide (TAF) or TDF.

DTG is a first-line ART recommended for HIV-positive adults and was recently named an alternative first-line therapy for non-pregnant adults, according to the NIH. DTG is beneficial because it is a once-daily therapy, has limited adverse events, has a high barrier to treatment-resistance, and is less costly.

Current research suggests that TAF and TDF have similar efficacy, but TAF comes with a lower risk of kidney- and bone-related adverse events.

There are limited data regarding the use of DTG and TAF in pregnancy, according to the release.

“Therapies for pregnant women and new mothers should be based on the best available evidence, always keeping in mind the health of the woman, her developing fetus and her newborn,” said Nahida Chakhtoura, MD, of the Maternal and Pediatric Infectious Disease Branch at National Institute of Child Health and Human Development. “The results of this study will help inform optimal treatment of pregnant women living with HIV in both resource-limited and well-resourced settings.”

The phase 3 IMPAACT 2010 clinical trial aims to enroll 639 pregnant women with HIV who are currently not treated with ART. Patients will be randomized to receive either EFV/FTC/TDF, DTG/FTC/TAF, or DTG/FTC/TDF.

Infants will also receive standard interventions for HIV prophylaxis following birth and mothers will be counseled on infant feeding options, according to the release.

The researchers will monitor the health of the mothers and infants for 50 weeks after delivery. Patients will receive counseling on ART adherence and viral loads will be monitored. Subsets of mothers and infants will also undergo bone density scans at 26 weeks.

The NIH expects the study to last for 3 years.

“Limited pregnancy data for newer, better antiretroviral drugs — such as DTG and TAF — can mean that pregnant women may not receive the most effective and safest medications, and can delay the general adoption of better regimens in low-resource settings with high HIV prevalence,” Dr Lockman said. “We hope that the trial will provide urgently needed information regarding the safety and efficacy of these newer drugs in pregnant women and their babies, so that optimal antiretroviral regimens can be offered to pregnant women and recommended for first-line treatment of adults living with HIV throughout the world.”