• Caitlin M Dugdale, Andrea L Ciaranello, Linda-Gail Bekker, Madeline E Stern, Landon Myer, Robin Wood, Paul E Sax, Elaine J Abrams, Kenneth A Freedberg, and Rochelle P Walensky.
• Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (C.M.D., A.L.C., K.A.F.).
• Ann. Intern. Med. 2019 May 7; 170 (9): 614625614-625.

BackgroundDolutegravir is superior to efavirenz for HIV antiretroviral therapy (ART) but may be associated with an increased risk for neural tube defects (NTDs) in newborns if used by women at conception.ObjectiveTo project clinical outcomes of ART policies for women of child-bearing potential in South Africa.DesignModel of 3 strategies: efavirenz for all women of child-bearing potential (EFV), dolutegravir for all women of child-bearing potential (DTG), or World Health Organization (WHO)-recommended efavirenz without contraception or dolutegravir with contraception (WHO approach).Data SourcesPublished data on NTD risks (efavirenz, 0.05%; dolutegravir, 0.67% [Tsepamo study]), 48-week ART efficacy with initiation (efavirenz, 60% to 91%; dolutegravir, 96%), and age-stratified fertility rates (2 to 139 per 1000 women).Target Population3.1 million South African women with HIV (aged 15 to 49 years) starting or continuing first-line ART, and their children.Time Horizon5 years.PerspectiveSocietal.InterventionEFV, DTG, and WHO approach.Outcome MeasuresDeaths among women and children, sexual and pediatric HIV transmissions, and NTDs.Results Of Base Case AnalysisCompared with EFV, DTG averted 13 700 women's deaths (0.44% decrease) and 57 700 sexual HIV transmissions, but increased total pediatric deaths by 4400 because of more NTDs. The WHO approach offered some benefits compared with EFV, averting 4900 women's deaths and 20 500 sexual transmissions while adding 300 pediatric deaths. Overall, combined deaths among women and children were lowest with DTG (358 000 deaths) compared with the WHO approach (362 800 deaths) or EFV (367 300 deaths).Results Of Sensitivity AnalysisWomen's deaths averted with DTG exceeded pediatric deaths added with EFV unless dolutegravir-associated NTD risk was 1.5% or greater.LimitationUncertainty in NTD risks and dolutegravir efficacy in resource-limited settings, each examined in sensitivity analyses.ConclusionAlthough NTD risks may be higher with dolutegravir than efavirenz, dolutegravir will lead to many fewer deaths among women, as well as fewer overall HIV transmissions. These results argue against a uniform policy of avoiding dolutegravir in women of child-bearing potential.Primary Funding SourceNational 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.

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