(Reuters Health) – The AIDS drug dolutegravir poses a small but significant risk of causing neural-tube defects for newborns when HIV-infected mothers are taking the drug when they conceive, according to surveillance data from hospitals throughout Botswana.
The study, reported at the 10th International AIDS Society Conference in Mexico City and online July 22 in the New England Journal of Medicine, adds to earlier work released in 2018 that found evidence of an even higher risk among recipients of dolutegravir, sold under the brand name Tivicay by Viiv Healthcare, which is mostly owned by GlaxoSmithKline.
Trained midwives identified five neural-tube defects among 1,683 babies whose mothers were taking the drug at conception, for a rate of 0.3%.
In contrast, the survey of 14,792 other deliveries where women were taking other antiretroviral drugs found a rate of 0.1%.
The rate among mothers who began taking the drug after conception was 0.03%.
With the earlier study “and the preliminary signal being close to 10 times higher than the other exposure groups, it did halt dolutegravir use in a lot of high-incidence HIV countries while people awaited more data, and it also changed guidelines in the U.S. and Europe for women who were planning a pregnancy,” chief author Dr. Rebecca Zash, an infectious disease specialist at Beth Israel Deaconess Medical Center in Boston, told Reuters Health in a telephone interview.
“The way people see this new data is that the risk of neural tube defects is really small even if it’s persistent – on the order of 2 extra neural tube defects per 1000 cases of exposure,” she said. “What has also become clear is all the benefits of dolutegravir, which wasn’t part of the original conversation. When weighing the benefits against this one small risk, it’s going to allow for much more widespread use of dolutegravir even among women of reproductive potential.”
Compared to older drugs, she said, dolutegravir “is tolerated much better with fewer side effects, it has few drug–drug interactions, and overall it seems to have better viral efficacy than most of the other antiretrovirals,” she said.
“So in a lot of parts of the world, a lot of people will go back to prescribing this in most circumstances,” Dr. Zash predicted. “I’m not sure what prescribers will do in the U.S. and Europe where there are a lot more choices and a lot more individualization of retroviral choices compared, for example, to Africa, where it’s more regimented.”
Botswana was the first African country to shift from efavirenz to dolutegravir as a first-line drug in 2016. The country provides free HIV treatment to all citizens.
The five defects seen in the new study were two cases of myelomeningocele, where the backbone and spinal canal have not closed, and one case each of encephalocele, which produces sac-like protrusions of the brain and protective membranes, anencephaly, where the major parts of the brain, skull and scalp do not form completely, and iniencephaly, where the child is born with its head bent backwards.
The Zash team initially looked for neural tube defects in patients receiving efavirenz because the defects were seen in a study in monkeys given the drug. That turned out to be a false alarm. Dolutegravir’s ability to spark the defects was unexpected.
The rate of neural tube defects in the general Botswana population was 0.08%.
N Engl J Med 2019