ABSTRACT/SUMMARY In our 2018 Lancet HIV commentary (“Ending AIDS by 2030: Catchy slogan or sincere goal?"), we note that published surveillance data together with mathematical modeling make it clear that UNAIDS 2030 goals (90% reduction in HIV incidence) are not going to be met with current spending and resource allocation, and UNAIDS 2020 goals (90% of infected are detected, 90% of detected are linked to care, and 90% of linked to care are virally suppressed) are not going to be met by 2020. Existing models suggest a tripling in HIV spending (from $12.8 billion to $40 billion per year) would be necessary to meet these goals, together with an optimizing of that spending. Indeed, without optimization, the necessary spending for that goal would likely top $52 billion per year. To achieve UNAIDS 2030 goals it will be necessary to critically assess the role of all available tools and tailor strategies to maximize their impact. However, current mathematical models omit three important tools in the arsenal for achieving 2030 goals in resource-limited regions: (1) Specific interventions that target the HIV care continuum (in particular specific interventions with randomized controlled-trial evidence include SMS-based text reminders for appointments and/or medications and combination interventions similar to Link4Health [including accelerated medication initiation, SMS-based text reminders, care/information package +/- noncash financial incentive]), (2) targeting interventions to high risk populations (such as those with alcohol use disorders [AUDs] and common mental disorders [CMDs]) that are specifically relevant to a region’s demographics and policy constraints, and (3) alternate timing of the peak of HIV spending (earlier is better because it leads to “getting ahead of the epidemic” but may be less feasible). Accordingly, focusing on the countries of Zimbabwe, eSwatini (formerly known as Swaziland), and South Africa (in particular, the province of KwaZulu Natal [KZN]) because of their disproportionate burden of HIV morbidity and mortality, our proposal uses mathematical modeling to evaluate the allocative efficiency of a wide spectrum of combination HIV prevention strategies to determine: How cost-effective would interventions enhancing ART linkage-adherence-retention (e.g., long acting ART) need to be in order to efficiently constitute combination HIV prevention strategy (Aim 1); How cost-effective would interventions enhancing PrEP linkage- adherence-retention (e.g., long-acting PrEP) need to be in order to efficiently constitute combination HIV prevention strategy (Aim 2); and how cost-effective would interventions enhancing PrEP and ART linkage- adherence-retention need to be in order to efficiently constitute combination HIV prevention strategy (Aim 3).