Congenital abnormalities increase with dolutegravir at conception

AMSTERDAM – There was a significant increase in the prevalence of neural tube defects in HIV-positive women who took dolutegravir (Tivicay) at conception compared with other antiretrovirals without dolutegravir (ARV), including Efavirenz (Sustiva), a researcher here

There were four cases of neural tube defects on 426 infants, but the prevalence in this group (0.94%, 95% CI 0.37% -2 , 4%) was higher than men on non-dolutegravir-based therapy at conception (0.12%, 95% CI 0.07% -0.21%) reported Rebecca Zash, MD, from Beth Israel Deaconess Medical Center in Boston

In addition, the prevalence of conbad abnormalities was higher in women taking dolutegravir compared to efavirenz (0.05%, 95% CI 0.02% -0.15% ).

The data from this late unplanned failure badysis was presented at a press conference at the International Conference on AIDS (IAC). in a correspondence published simultaneously in the New England Journal of Medicine

The study's authors were asked to provide preliminary data for the steering committee of HIV pregnancy guidelines, they said . In the end, these data triggered warnings from the FDA, the European Medicines Agency and the WHO regarding dolutegravir and its link to birth defects

Myron Cohen, MD, of University of North Carolina at Chapel Hill. "Given the importance of this agent for the treatment of HIV, it is urgent to study carefully the women who have documented the exposure to this agent at the time of conception," he added. . says MedPage today . "Public policy has already pushed providers of this drug for women of reproductive age The real problem to prove or disprove this risk as quickly as possible."

Recently, the WHO released updated interim guidelines, including a programmatic algorithm indicating that women can continue to take dolutegravir as long as they have access to "consistent and reliable contraception".

"Many people have interpreted this as the WHO and others saying that women should not take dolutegravir. it is clear that … this should not be a universal approach, "said Zash. "The question is how to make that a reality on the ground and give people the contraceptive access they need that allows them to make an informed choice with very preliminary data."

Zash adds that this study started in 2014 when dolutegravir "was not even used in Botswana". She stated that the study was originally designed to evaluate antiretroviral regimens, and that they were primarily interested in neural tube defects related to efavirenz (ibid.). which was part of the first-line antiretroviral therapy in Botswana at the time). In mid-2016, Botswana opted for first-line antiretroviral therapy, switching from an efavirenz-based regimen to a dolutegravir-based regimen, "becoming the first country to do so. all adults and pregnant women "

. a study was conducted in eight of Botswana's largest maternal hospitals, accounting for about 45 percent of all births in the country. Zash said that when an abnormality was noted in an infant, qualified midwives contacted research badistants involved in the study who asked the mothers to consent to a photograph of the abnormality. . The researchers identified 86 neural tube defects in 88,755 births (0.10%, 95% CI 0.08% -0.12%), including 42 meningoceles / myelomeningoceles, 30 anencephalias and 13 encephaloceles. Of these, 57% had photos and 43% had descriptions.

There were 14 neural tube defects out of 11,300 for non-dolutegravir treatment at conception and 3 out of 5,787 for efavirenz-based ART. For uninfected women, there were 61 neural tube defects out of 5,624 (0.05%, 95% CI 0.02% -0.16%).

Interestingly, there were no conbad malformations in 2812 women starting dolutegravir during pregnancy. Zash added that in the data on 170 additional births since May 2018, there were no conbad malformations in women under dolutegravir at conception (current prevalence 0.67%, 95% CI 0.26). % -1.7%).

Weighing Risks and Benefits

An accompanying editorial in NEJM by Sonja A. Rasmussen, MD, of the CDC, and colleagues cited the 'complicated' decisions about the treatment of HIV-infected pregnant women – – but pregnant women are almost always excluded from clinical trials, so information about treatment decisions is almost always inadequate.

"Therapeutic decisions during pregnancy will continue to be an exercise in balance based on available data and expert opinions" editorial writers have written. However, moving from the exclusion of pregnant women to careful consideration of benefits and risks can ensure that pregnant women and their fetuses receive the care they need.

Linda-Gail Bekker, MBChB, PhD, Desmond Tutu HIV Center in Cape Town, South Africa and President, International AIDS Society, who moderated the press conference, but did not participate In research, emphasized the importance of involving the patient in the discussion about treatment, including a discussion of different therapies. 19659006] "By listening to women at these conferences, they want to be included in the decision-making process, we will have to write this for health care workers on the front lines and I think this is happening quickly right now." says MedPage today .

Zash says the next scheduled badysis of the data will be March 2019. She added that if the safety signal is finally confirmed or refuted, these data have "highlighted the need for better access to contraception , better patient-centered care in areas of high HIV prevalence and better systems for studying the safety of ARVs during pregnancy. "

1969-12-31T19: 00: 00-0500

Last updated ] 07.24.2018