BackgroundIn recent years, safer conception strategies have been developed to help HIV-serodiscordant couples conceive a child without transmitting HIV to the seronegative partner. The SAFER clinical trial assessed implementation of these strategies in Zimbabwe.MethodsAs a part of the SAFER study, we estimated the costs (in 2017 US)associatedwithindividualandcombinationstrategies,inthetrialsettingandreal−worldpractice,fromahealthcaresystemperspective.Saferconceptionstrategiesincluded:1)ARTwithfrequentviralloadtestinguntilachievingundetectableviralload(ART−VL);2)dailyoralpre−exposureprophylaxis(PrEP);3)semen−washingwithintrauterineinsemination;and4)manualself−inseminationathome.Forcostsinthetrial,weusedamicro−costingapproach,includingatimeandmotionstudytoquantifypersonneleffort,andestimatedthecostpercoupleforindividualandcombinationstrategiesforameanof6 monthsofsaferservices.Forreal−worldpractice,wemodeledcostsforthreeimplementationscenarios,representingdifferencesfromthetrialininputprices(paidbytheMinistryofHealthandChildCare[MOHCC]),interventionintensity,andincrementstocurrentHIVpreventionandtreatmentpracticesandguidelines.Weusedone−waysensitivityanalysestoassesstheimpactofuncertaintyininputvariables.ResultsIndividualstrategycostswere769-1615percoupleinthetrial;185-563ifusingMOHCCprices.UnderthetargetinterventionintensityandusingMOHCCprices,individualstrategycostswere73-360percoupleoverandabovethecostofcurrentHIVclinicalpractices.Thecostofdeliveringthemostcommonlyselectedcombination,ART−VLplusPrEP,rangedfrom166-$517 per couple under the three real-world scenarios. Highest costs were for personnel, lab tests, and strategy-specific consumables, in variable proportions by clinical strategy and analysis scenario. Total costs were most affected by uncertainty in the price of PrEP, number of semen-washing attempts, and scale-up of semen-washing capacity.ConclusionsSafer conception methods have costs that may be affordable in many low-resource settings. These cost data will help implementers and policymakers add safer conception services. Cost-effectiveness analysis is needed to assess value for money for safer conception services overall and for safer strategy combinations.Trial registrationRegistry Name: Clinicaltrials.gov.Trial registration numberNCT03049176 . Registration date: February 9, 2017