Dolutegravir-based antiretroviral therapy (ART) may lead to both fewer deaths in women and fewer overall HIV transmissions, according to study results published in the Annals of Internal Medicine.
Currently, efavirenz-based ART is recommended by the World Health Organization (WHO) as the preferred first-line regimen for people with HIV, but dolutegravir-based ART may offer superior tolerability and efficacy. However, preliminary data revealed a higher risk of neural tube defects (NTDs) in infants born to women who conceived while receiving dolutegravir (0.94%) compared with women receiving efavirenz (0.05%). Therefore, WHO recommended efavirenz as a safe and effective alternative for women of childbearing potential desiring pregnancy or lacking access to reliable and consistent contraception. However, from the public health, clinical, and patient perspective, the risk for developing NTDs potentially attributable to dolutegravir should be weighed against the benefits of dolutegravir over efavirenz, which include increasing sustained virologic suppression and therefore improving outcomes and reducing HIV transmission. Thus, this study aimed to project clinical outcomes of ART policies for women of childbearing potential in South Africa.
A total of 3.1 million South African women with HIV (aged 15 to 49 years) who were starting or continuing first-line ART were included in the study, along with their children. Over 5 years, 3 model approaches were used: efavirenz for all women of childbearing potential, dolutegravir for all women of childbearing potential, or WHO-recommended efavirenz without contraception or dolutegravir with contraception (WHO). Outcomes for the WHO approach were calculated as a weighted average of the dolutegravir and efavirenz strategies based on contraceptive use. Measured outcomes included mortality in women and children, sexual and pediatric HIV transmissions, and NTDs.
Results showed that combined deaths in women and children were lowest with the dolutegravir approach (13,700 fewer deaths in women and 2100 fewer NTD-related deaths in children) when compared with either the WHO approach (362,800 deaths) or the efavirenz approach (367,300 deaths). The dolutegravir approach and the WHO approach decreased women’s deaths, increased virologic suppression, and decreased sexual HIV transmissions compared with efavirenz. However, treatment with dolutegravir showed an increase in total pediatric deaths by 4400 incidents as a result of NTDs. The WHO approach had more benefits than efavirenz, which included averting 4900 women’s deaths and 20,500 sexual HIV transmissions but added 300 pediatric deaths.
Overall, the study authors concluded that, “These results argue against a blanket policy of favoring efavirenz over dolutegravir in women of childbearing potential. Rather, this study supports an open, context-specific discussion about the tradeoffs between the risks for harm and the benefits of these treatment options.”
The primary funding sources for this study include: National Institutes of Health, National Institute of Allergy and Infectious Diseases and Eunice Kennedy Shriver National Institute of Child Health and Human Development, Massachusetts General Hospital, and Harvard University Center for AIDS Research.
Dugdale CM, Ciaranello AL, Bekker LG, et al. Risks and benefits of dolutegravir- and efavirenz-based strategies for South African women with HIV of child-bearing potential [published online April 2, 2019]. Ann Intern Med. doi:10.7326/M18-3358