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As part of a program to prevent the transmission of HIV from mother to child, social workers in Francistown, Botswana, staged a skit in a parking lot. supermarket.
Malcolm Linton
Dolutegravir, which has the reputation of being the best of 32 marketed antiretroviral drugs, was severely affected in May by Preliminary analysis of a study that included more than 10,000 HIV-positive pregnant women in Canada. Botswana has revealed that it can lead to serious birth defects. Today, at the International AIDS Conference in Amsterdam, researchers reported more data from this study that suggests that the risk of harm may be lower than the first thought. But troubling questions remain about her safety during pregnancy and whether programs that plan to promote her widely should restrict her use in women of childbearing age.
The potential problem with dolutegravir surfaced because of concerns about another anti-HIV drug, efavirenz, which caused what are known as neural tube defects in neonatal monkeys . In 2014, researchers in Botswana undertook a four-year surveillance study, dubbed Tsempano, of all babies born to HIV infected and uninfected mothers in eight clinics to assess the frequency of neuronal abnormalities. This rare disease can cause big holes in the spine or can prevent the formation of the skull top. Two years later, before these results are known, Botswana has made dolutegravir a treatment of choice because it suppresses HIV in a powerful way, people tolerate it well and drug resistance rarely surfaces.
In April, the World Health Organization (WHO) in Geneva, Switzerland, contacted the Tsempano team to help it prepare new guidelines for infected pregnant women by HIV. There was little data on dolutegravir, and Botswana was a great place to look for clues: the study was already underway, capturing about 45% of births in the country, and the prevalence of HIV prevalence there. is high. When the researchers took a look at their data, they found an association between neural tube defects and dolutegravir, and not efavirenz. "We were extremely surprised," says Rebecca Zash, an infectious disease specialist and co-principal investigator of the study, based at the Beth Israel Deaconess Medical Center in Boston. "We thought we had done something wrong."
On May 18, the WHO issued an "alert" warning about the potential danger. Many countries had planned this year to start using dolutegravir – which is available in a cheap generic combination with other drugs – but these results hit the pause button on what was going to be a global drug promotion .
The New England Medical Journal ( NEJM ) published today's May data in an online report, a few hours before Zash presented a last week. As the document NEJM explains their initial analysis involved 89,064 births. About 75% of the babies studied are born to mothers who are not infected with HIV. There were 86 neural tube defects in all, a rate of 0.1% of births. Among HIV-infected mothers, 14 women took antiretrovirals other than dolutegravir, a rate of 0.12%. But in 426 women who took dolutegravir before conception, the researchers found four cases of neuronal defects – a rate of 0.94%, about nine times higher than the other groups. No cases have been found in pregnant women who started the drug during pregnancy. Neural tube formation occurs during the first 28 days of pregnancy.
At a conference session, Zash reported new data on 170 new babies born to mothers who took dolutegravir before conception. They no longer found cases of neural tube defects, dropping the rate to 0.67%, which is still six times higher than with other antiretrovirals. She pointed out that new discoveries do not clean the air. "It's still a preliminary signal and we need more data to confirm or refute it," says Zash. "It would be as good to have data from other parts of the world."
Maggie Little, bioethicist of the Kennedy Institute of Ethics of Georgetown University in Washington, DC, specializing in bioethics research and reproductive life of women Too few studies are intentionally evaluating the study. the impact of antiretrovirals on pregnant women who, for safety reasons, are systematically excluded from clinical trials, according to Little. . "This study was almost an accident," she adds, noting that it was designed to evaluate the damage done by efavirenz, and not by dolutegravir. "Why do we leave this to chance?"
Lynne Mofenson, pediatrician, who works with the Elizabeth Glaser Pediatric AIDS Foundation in Washington, DC, chaired the session and provided insight into neural tube defects and antiretrovirals. "We have no completely safe antiretroviral therapy," she said. "It's a question of benefit versus risk." And for dolutegravir, this equation is tricky because the drug works exceptionally well to suppress the virus for long periods of time, which clearly benefits the mother. "Often, I have the impression that we are in a boxing match between a baby and a mother and that we oppose each other," says Mofenson
. 18 clinics, which should capture nearly 75% of all births in the country. In March 2019, they calculate that they will have data on 1,200 babies born to mothers who started the drug preconception. If there are more neural tube defects in this group, the risk presented by dolutegravir will not be different from that of other antiretrovirals, she says. "We will feel very reassured."
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