AbstractIntroductionDespite widespread success in reducing vertical HIV transmission, most antenatal care (ANC) programmes in eastern and southern Africa have not emphasized primary prevention of maternal HIV acquisition during pregnancy and lactation/breastfeeding. We hypothesized that combination HIV prevention interventions initiated alongside ANC could substantially reduce maternal HIV incidence.MethodsWe constructed a multi‐state model describing male‐to‐female HIV transmission in steady heterosexual partnerships during pregnancy and lactation/breastfeeding, with initial conditions based on population distribution estimates for Malawi and Zambia in 2020. We modelled individual and joint increases in three HIV prevention strategies at or soon after ANC initiation: (1) HIV testing of male partners, resulting in HIV diagnosis and less condomless sex among those with previously undiagnosed HIV; (2) initiation (or re‐initiation) of suppressive antiretroviral therapy (ART) for male partners with diagnosed but unsuppressed HIV; and (3) adherent pre‐exposure prophylaxis (PrEP) for HIV‐negative female ANC patients with HIV‐diagnosed or unknown‐status male partners. We estimated the percentage of within‐couple, male‐to‐female HIV transmissions that could be averted during pregnancy and lactation/breastfeeding with these strategies, relative to base‐case conditions in which 45% of undiagnosed male partners become newly HIV diagnosed via testing, 75% of male partners with diagnosed but unsuppressed HIV initiate/re‐initiate ART and 0% of female ANC patients start PrEP.ResultsIncreasing uptake of any single strategy by 20 percentage points above base‐case levels averted 10%−11% of maternal HIV acquisitions during pregnancy and lactation/breastfeeding in the model. Joint uptake increases of 20 percentage points in two interventions averted an estimated 19%−23% of transmissions, and with a 20‐percentage‐point increase in uptake of all three interventions, 29% were averted. Strategies achieving 95% male testing, 90% male ART initiation/re‐initiation and 40% female PrEP use reduced incident infections by 45%.ConclusionsCombination HIV prevention strategies provided alongside ANC and sustained through the post‐partum period could substantially reduce maternal HIV incidence during pregnancy and lactation/breastfeeding in eastern and southern Africa.