In low- and middle-income countries, dolutegravir (Tivicay) uptake in women still trailed that in men months after a safety reaffirmation from the World Health Organization (WHO), a large study showed.

By March 2020, cumulative incidence of uptake of the antiretroviral by women ages 16-49 was 29.4% across 11 countries, compared with 57.7% in men of the same age group. Uptake incidence was lowest in women 16-29 years old, at only 14.2%, Denis Nash, PhD, MPH, of the City University of New York, and colleagues reported.

“If sustained, this disparity could have implications for HIV treatment outcomes because of the superior efficacy and tolerability of dolutegravir and its anticipated population health benefits,” the authors wrote in the Annals of Internal Medicine.

In May 2018, just after its initial recommendation of dolutegravir as part of the preferred first- and second-line regimens for adults and adolescents with HIV, the WHO cautioned against dolutegravir use in women of reproductive age after concerns were raised about infant neural tube defects in the Tsepamo cohort in Botswana.

However, further studies later determined that this association was not statistically significant. In 2019, the WHO reinstated its recommendation of dolutegravir as the preferred antiretroviral therapy (ART) for women with HIV.

Prior to the WHO’s 2019 safety statement on dolutegravir, the ratio of cumulative incidence of dolutegravir uptake in women to men was 0.40 for the 16-49 age group. That ratio improved somewhat to 0.51 after the revised recommendation, according to Nash’s group.

“The clear effect [of the initial warning] was to steer women of childbearing potential back to older, less effective, and less well-tolerated regimens,” Andrea Ciaranello, MD, MPH, of Harvard Medical School in Boston, and colleagues wrote in a corresponding editorial.

This study on dolutegravir gives “a poignant example of how far we remain from prioritizing women’s decision-making autonomy and health and from having timely, high-quality data for drugs used during pregnancy and breastfeeding,” Ciaranello and colleagues said.

Pregnant women historically have been excluded from clinical trials. Most recently, pregnant women were excluded from COVID-19 vaccine clinical trials. While later data confirmed the safety of vaccines for pregnant women, fewer pregnant women opted to get the vaccine during its initial rollout.

For dolutegravir’s predecessor, efavirenz (Sustiva), there had also been initial concerns about neural tube defects in 2006 that later abated with better evidence. Only in 2013 did the WHO recommend efavirenz for all adults and adolescents including women. In women ages 16-49, efavirenz is now the most prevalent ART, according to Nash and colleagues.

Their study measured dolutegravir use from January 2017 to March 2020. It included 134,672 people from 11 countries participating in the International epidemiology Databases to Evaluate AIDS. Only sites with more than 50 patients and 1% or more documented dolutegravir use were included. Women ages 16-49 comprised 52% of the cohort, whereas only 25% were men from the same age group.

In men and women over the age of 50, there were no significant disparities in dolutegravir uptake.

Nash and coauthors acknowledged that the study population may not be representative of a specific country or region. They also noted that their data was collected prior to the pandemic, which has since negatively impacted HIV care delivery.