Based on new evidence assessing benefits and risks, the World Health Organization has announced its recommendation on the use of the HIV drug dolutegravir (DTG) as the preferred first line and second-line treatment for all populations, including pregnant women and those of childbearing potential.
Initial studies had highlighted a possible link between DTG and neural tube defects (birth defects of the brain and spinal cord that cause conditions such as spina bifida) in infants born to women using the drug at the time of conception. This potential safety concern was reported in May 2018 from a study in Botswana that found 4 cases of neural tube defects out of 426 women who became pregnant while taking DTG. Based on these preliminary findings, many countries advised pregnant women and women of childbearing potential to take efavirenz (EFV) instead.
WHO says new data from two large clinical trials comparing the efficacy and safety of DTG and EFV in Africa have now expanded the evidence base. The risks of neural tube defects are significantly lower than what the initial studies may have suggested.
A report from the National Institutes of Health (NIH), released the same day as the WHO release, says children born to women on HIV therapy containing the drug dolutegravir since conception have a slightly higher risk of neural tube defects, compared to children born to women on regimens of other antiretroviral drugs.
Those findings are from a study funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), part of the National Institutes of Health, and were presented at the 10th International AIDS Society Conference in Mexico City by Rebecca Zash, M.D., of Beth Israel Deaconess Medical Center in Boston. The study also appears online in the New England Journal of Medicine.
For women on dolutegravir since conception, five neural tube defects occurred out of 1,683 births (.3 percent). For women on the drug efavirenz since conception, there were three cases of neural tube defects out of 7,959 births (.04 percent). For women on any HIV treatment regimens that did not contain dolutegravir, there were 15 neural tube defect cases out of 14,792 births (.1 percent). Overall, the researchers found a .2 percent difference in risk for children born to women on dolutegravir since conception, which they described as small, but significant.
Meanwhile, WHO says the guidelines group also considered mathematical models of the benefits and harms associated with the two drugs; the values and preferences of people living with HIV, as well as factors related to implementation of HIV programs in different countries, and cost.
DTG is a drug that is more effective, easier to take and has fewer side effects than alternative drugs that are currently used. DTG also has a high genetic barrier to developing drug resistance, which is important given the rising trend of resistance to EFV and nevirapine-based regimens. In 2019, 12 out of 18 countries surveyed by WHO reported pre-treatment drug resistance levels exceeding the recommended threshold of 10 percent.
All of above findings informed the decision to update the 2019 guidelines, WHO said.
