In a cautiously optimistic report, researchers described pregnancy outcomes in 25 women living with HIV in clinical trials of a new long-acting injectable antiretroviral therapy of cabotegravir and rilpivirine (CAB+RPV).
Among 10 live births there was a birth defect (congenital ptosis or drooping eyelid), which was not attributed to the test drugs. There were no cases of perinatal HIV transmission at delivery or during the one-year follow-up.
Parul Patel, PharmD
“Long-acting cabotegravir-rilpivirine is the first and only complete injectable regimen potentially available to pregnant women,” said first author Parul Patel, PharmD, global medical affairs director for cabotegravir at ViiV Healthcare, in an interview. with Medscape Medical News. The diet was approved by the United States Food and Drug Administration in January 2021 for injections every 4 weeks and in February 2022 for injections every 8 weeks.
“It’s important to note that it can be dosed monthly or every 2 months,” Patel said. “This could be beneficial for women who go through constant changes during pregnancy. This could be a consideration for women who may have problems tolerating oral pills during pregnancy or who may have problems with vomiting.”
The study was published in HIV medicine.
“We are really pursuing development of the long-acting version of cabotegravir in combination with rilpivirine,” Patel said. “It’s an industry standard during initial development that you start out very conservatively and not allow a pregnant woman to continue dosing a drug while evaluating its overall safety profile. We really want to understand the use of this agent in non-pregnant adults before exposing pregnant women to active treatment.
Pregnancies in trials excluding pregnant women
In the article, Patel and co-authors noted the limited data on pregnant women exposed to CAB+RPV. They analyzed pregnancies in four Phase 2b/3/3b clinical trials sponsored by ViiV Healthcare and a compassionate use program. All clinical trial participants initially received oral CAB + RPV daily for 4 weeks to assess individual tolerance before experimental long-acting injection of CAB + RPV every 4 weeks or every 8 weeks .
Participants had to use highly effective contraception during the trials and for at least 52 weeks after the last injection. Urine pregnancy tests were administered at baseline, before each injection and if pregnancy was suspected. If pregnancy was detected, CAB + RPV (oral or long-acting injections) was discontinued and the woman was switched to another oral antiretroviral, unless she and her doctor decided to continue the injections as part of the treatment schedule. compassionate use.
Pregnancy results
Of the 25 pregnancies reported in 22 women during the trial, there were 10 live births. Nine of the mothers who delivered at term had switched to alternative antiretroviral therapy and maintained virologic suppression throughout pregnancy and postpartum, or the last available viral load assessment.
The 10th participant remained on long-acting CAB+RPV during her pregnancy and had a live birth with congenital ptosis that resolved without treatment at the 4-month ophthalmology visit, the authors wrote. The mother presented with persistent low-grade viremia before and throughout her pregnancy.
Two of the pregnancies occurred after the last monthly injection, during the withdrawal period. Other studies have reported that each long-acting drug, CAB and RPV, can be detected more than a year after the last injection. In the new report, plasma concentrations of CAB and RPV during pregnancy were within the range of those in non-pregnant women, the authors wrote.
Of the 14 participants whose birth was not live, 13 switched to alternative antiretroviral therapy during pregnancy and maintained virologic suppression during pregnancy and postpartum, or until their last viral evaluation. The remaining participant received a long-acting CAB + RPV and continued this treatment throughout her pregnancy.
“This is a very limited data set, so we are unable to draw firm conclusions on long-acting cabotegravir-rilpivirine in pregnancy,” Patel acknowledged. “But the data we presented among the 25 women who were exposed to cabotegravir-rilpivirine seem reassuring.”
Planned studies during pregnancy
Vani Vannappagari, MBBS, MPH, PhD, global head of epidemiology and real-world evidence at ViiV Healthcare and study co-author, said Medscape Medical News that early results stimulate promising new research.
“We work with an external IMPAACT [International Maternal Pediatric Adolescent AIDS Clinical Trials Network] group on a clinical trial…to try to determine the appropriate dose of long-acting cabotegravir-rilpivirine during pregnancy,” Vannappagari said. “The clinical trial will give us immediate safety, dose information and viral suppression rates for mother and infant. But long-term safety, especially birth defects and any adverse pregnancy and newborn outcomes, will come from our antiretroviral pregnancy registry and other non-interventional studies.
“In the very small cohort studied, [in] pregnancies that continued after exposure to cabotegravir and long-acting rilpivirine during the first trimester, no significant adverse fetal outcomes were identified,” he said. “It’s reassuring, as is the fact that at the time these patients were changed in early pregnancy, their viral loads were all undetectable at the time their pregnancies were diagnosed.”
Neil Silverman, MD, professor of clinical obstetrics and gynecology and director of the Infections in Pregnancy program at UCLA Medical Center in Los Angeles, Calif., who was not associated with the study, provided a comment to Medscape Medical News.
“The larger question remains why pregnant women were so actively excluded from the original study design when this trial was evaluating a new long-acting preparation of two anti-HIV drugs that would otherwise be perfectly usable during pregnancy. pregnancy ?”
Silverman continued, “In this case, it is particularly frustrating since the current study was simply evaluating established drugs currently used to manage HIV infection, but in a new, longer-acting mode of administration by injection every 2 months. If a patient had previously been successfully managed on an oral antiviral regimen containing an integrase inhibitor and a non-nucleoside reverse transcriptase inhibitor, such as the two drugs studied here, it would not be considered reasonable to simply change that regimen because she turned out to be pregnant.
Parul Patel and Vani Vannappagari are employees of ViiV Healthcare and shareholders of GlaxoSmithKline.
This analysis was funded by ViiV Healthcare, and all studies were co-funded by ViiV Healthcare and Janssen Research & Development. Silverman reported no relevant financial relationships.
HIV drug. Published online November 21, 2022. Full text
Myles Starr is a medical journalist based in New York.
For more news, follow Medscape on Facebook, TwitterInstagram and YouTube
#Pregnancy #outcomes #longacting #antiretroviral