Using raltegravir (brand name Isentress) for antiretroviral therapy before and during pregnancy was not associated with birth defects, a new study found.
"The data is reassuring that if you have a an HIV-positive woman who has childbearing potential or interested in becoming pregnant, or is pregnant, and contemplating what [antiretroviral] therapy to put them on, raltegravir is something you should consider because of the safety track record," said Hala Shamsuddin, M.D., clinical safety and risk management researcher with Merck & Co., who presented these findings at the IDWeek 2019 Conference in early October.
The study Shamsuddin presented was funded by Merck (the manufacturers of raltegravir) to evaluate the safety of their drug in pregnancy. They wanted to examine people who were living with HIV and using raltegravir as part of their antiretroviral therapy prior to becoming pregnant. The researchers decided to use a prospective analysis of reports "which are received prior to knowledge of pregnancy outcome or prior to the detection of congenital malformation at prenatal examination." In other words, the study looked at people who used raltegravir before pregnancy, and then were able to use pregnancy as a baseline to then evaluate the impact of the drug as a cause of any adverse events on a forming fetus.
They reviewed 2,508 pregnancy exposures reported to the company's safety database and two existing cohorts of people living with HIV in the United States, the United Kingdom, Ireland, and France. They reviewed exposures from the beginning of the drug's approval in 2007 through March 26, 2019 and divided those that were exposed to the drug during the first trimester and those within the first month of conception. Nearly all of the prospective reports were in people using the 400 mg tablet twice daily. They reviewed any reported spontaneous abortion, stillbirth, and congenital abnormalities -- including neural tube defects.
"Subsequent to the publication of the description of the association of neural tube defects following 30 conception exposures to dolutegravir, there was some regulatory action taken, updating the labeling of dolutegravir and bictegravir in the United States," said Shamsuddin. "So the question came up whether this birth defect represents a class defect."
Of the 471 documented first-trimester exposures, researchers found "the rates of spontaneous abortion (6.9%), stillbirth (1%), and congenital anomalies (1.5% per live births)." They found that these defects were "similar to the rates observed in the background populations of the U.S." They also found that no neural tube defects were reported at all -- which typically form within the first 28 days of conception.
This research is important, as an increased focus on the use of antiretrovirals in pregnancy and the inclusion of women in clinical research as principal investigators emerges, as well as ensuring that new drugs are both safe and efficacious for women in general and for women who want to conceive and have children.
"Usually when it comes to the market, there's very little data on pregnancy, as you know," said Shamsuddin. "Pregnant women are generally not enrolled in clinical trials, and when they are, if they get pregnant, they are discontinued from the trial."
"I think also that because of this scenario, with all the types of error and not having good information on pregnant women, I think there's a strong interest in allowing pregnant women to participate in clinical trials, and not to automatically discontinue them just because they get pregnant," added Wayne Greaves, M.D., executive director of infectious disease with Merck. "But to give adequate informed consent, double consent if necessary, so they understand the risk. Because there are women, because of the benefits of taking these drugs during pregnancy, [who] would want to continue, we just haven't given them that choice. I think what we've come to now realize is that we need to give women some choice and some empowerment to stay in clinical trials, because this will provide us some data that we don't have."