The integrase inhibitor dolutegravir (DTG) could have a major role in future antiretroviral therapy (ART) regimens in sub-Saharan Africa because of its high potency, barrier to resistance, tolerability, and low cost, but there is uncertainty over appropriate policies for use relating to the potential for drug resistance spread and a possible increased risk of neural tube defects in infants if used in women at the time of conception. This study used an existing individual-based model of HIV transmission, progression, and the effect of ART with the aim of informing policy makers on approaches to the use of DTG that are likely to lead to the highest population health gains.