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Issues about periconception use of dolutegravir are reminiscent of early concerns about efavirenz. South Africa intends to include dolutegravir in its first-line antiretroviral therapy (ART) regimen because of cost savings, the drug's high barrier to resistance, and efficacy. However, recent data from Botswana suggest potential teratogenicity of dolutegravir. WHO recommends that non-pregnant women of childbearing age who are not using an effective form of contraception and women in early pregnancy should not initiate treatment with dolutegravir. Similar concerns about efavirenz once existed; the 2010 South African ART guidelines recommended that pregnant women and women at-risk of pregnancy should not be given efavirenz. Screening of fertility intentions and contraceptive use were poor, and protocols for regimen changes were unevenly implemented across South Africa. High incidence of unplanned pregnancies and late pregnancy diagnosis resulted in delays in efavirenz substitution. In the absence of reassuring safety data on dolutegravir, South Africa should learn from past mistakes and develop systems to ensure improved communication with patients and better integration of comprehensive reproductive health services.