NIH launches phase 3 trial assessing dolutegravir in pregnant women

The NIH announced that it has launched a large international trial to compare the safety and efficacy of current WHO-recommended first-line ART and two other HIV regimens containing dolutegravir in pregnant women.

The trial, known as IMPAACT 2010 or VESTED, will examine how each regimen affects viral load as well as rates of adverse pregnancy outcomes, maternal adverse events and infant adverse events, according to press release.

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

WHO currently recommends that pregnant women with HIV in resource-limited settings receive an ART regimen containing efavirenz (EFV), lamivudine (3TC) or emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF). However, this regimen is not well-tolerated and may not be appropriate for all women, according to the NIH. EFV is associated with liver problems and neuropsychiatric symptoms such as suicidal thoughts, and TDF has been linked to adverse kidney events and bone mineral density loss in adults. There is also evidence that TDF may cause bone loss in infants with prenatal exposure, the release said.

Dolutegravir (DTG) is in two preferred first-line ART regimens for adults with HIV in the United States. The drug was also recently included in WHO guidelines as an alternative to first-line therapy in nonpregnant adults. It has several advantages, according to the NIH, including once-daily dosing, a good safety profile, a high barrier to resistance and low production cost. However, few studies have evaluated DTG in pregnancy.

The 3-year, phase 3 VESTED trial is expected to enroll 639 women with HIV who are 14 to 28 weeks pregnant in the U.S., Zimbabwe, Botswana, Brazil, Haiti, India, Malawi, South Africa, Tanzania, Thailand and Uganda, according to the release. The study participants will be randomly assigned to EFV/FTC/TDF, DTG/FTC/tenofovir alafenamide (TAF) or DTG/FTC/TDF. After delivery, their infants will receive standard-of-care interventions for HIV prophylaxis. Researchers will monitor mothers and infants for 50 weeks after birth and conduct bone density scans in a subset of infants at 26 weeks and mothers at 50 weeks postpartum.

“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,” Shahin Lockman, MD, MSc, study co-chair and associate physician at Brigham and Women’s Hospital, said in the release. “We hope that the VESTED 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.”

EFV is sold under the brand name Sustiva (Bristol-Myers Squibb), TDF is sold under the brand name Viread (Gilead Sciences) and TAF is sold under the brand name Vemlidy (Gilead Sciences) in the U.S.

Disclosures: Infectious Disease News was unable to confirm relevant financial disclosures for Lockman at the time of publication.

The NIH announced that it has launched a large international trial to compare the safety and efficacy of current WHO-recommended first-line ART and two other HIV regimens containing dolutegravir in pregnant women.

The trial, known as IMPAACT 2010 or VESTED, will examine how each regimen affects viral load as well as rates of adverse pregnancy outcomes, maternal adverse events and infant adverse events, according to press release.

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

WHO currently recommends that pregnant women with HIV in resource-limited settings receive an ART regimen containing efavirenz (EFV), lamivudine (3TC) or emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF). However, this regimen is not well-tolerated and may not be appropriate for all women, according to the NIH. EFV is associated with liver problems and neuropsychiatric symptoms such as suicidal thoughts, and TDF has been linked to adverse kidney events and bone mineral density loss in adults. There is also evidence that TDF may cause bone loss in infants with prenatal exposure, the release said.

Dolutegravir (DTG) is in two preferred first-line ART regimens for adults with HIV in the United States. The drug was also recently included in WHO guidelines as an alternative to first-line therapy in nonpregnant adults. It has several advantages, according to the NIH, including once-daily dosing, a good safety profile, a high barrier to resistance and low production cost. However, few studies have evaluated DTG in pregnancy.

The 3-year, phase 3 VESTED trial is expected to enroll 639 women with HIV who are 14 to 28 weeks pregnant in the U.S., Zimbabwe, Botswana, Brazil, Haiti, India, Malawi, South Africa, Tanzania, Thailand and Uganda, according to the release. The study participants will be randomly assigned to EFV/FTC/TDF, DTG/FTC/tenofovir alafenamide (TAF) or DTG/FTC/TDF. After delivery, their infants will receive standard-of-care interventions for HIV prophylaxis. Researchers will monitor mothers and infants for 50 weeks after birth and conduct bone density scans in a subset of infants at 26 weeks and mothers at 50 weeks postpartum.

“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,” Shahin Lockman, MD, MSc, study co-chair and associate physician at Brigham and Women’s Hospital, said in the release. “We hope that the VESTED 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.”

EFV is sold under the brand name Sustiva (Bristol-Myers Squibb), TDF is sold under the brand name Viread (Gilead Sciences) and TAF is sold under the brand name Vemlidy (Gilead Sciences) in the U.S.

Disclosures: Infectious Disease News was unable to confirm relevant financial disclosures for Lockman at the time of publication.