Introduction Swaziland has the highest global HIV prevalence with an estimated 27% of people aged 15–49 living with HIV. To address this issue, the Government aimed to optimise HIV investment by assessing the impact of key interventions.

Methods We used Optima to assess the impact of moderate- and high-level scale-up of five interventions: scaling-up antiretroviral therapy (ART) coverage to 65% (at CD4 count <500 cells/mm³) by 2020 and 75% by 2030 (moderate scale-up) or 85% by 2020 and 90% by 2030 (high-level scale-up), voluntary medical male circumcision (VMMC) to 55% by 2018 (moderate) or 45% by 2015 and 70% by 2018 (high-level) for males aged 10−49, prevention of mother-to-child transmission to 90% (moderate) or 95% (high-level) by 2018, tuberculosis/HIV co-treatment to 75% by 2015, 85% by 2018, and 90% by 2030 (moderate) or similar targets for high-level scale-up except with 95% coverage by 2030, and implementation of conditional cash transfers (CCT) to 60% (moderate) or 95% (high-level) by 2018 for women aged 15–24. Data were provided by the Swaziland Government for general and key populations disaggregated by age and sex for 2000−2013.

Results By 2030, compared to current coverage, it is possible to reduce new infections by 27% and AIDS-related deaths by 12% (moderate scale-up) or by 49% and 24%, respectively, with high-level scale-up. The highest impact interventions are ART, VMMC, and CCT.

The discounted cumulative additional program cost of these combined interventions was US$74 million with an incremental cost-effectiveness ratio of US$2,700 per infection averted (for moderate scale-up) and US$309 million with an incremental cost-effectiveness ratio of US$6,300 per infection averted (for high level scale-up).

Conclusion Rapid scale-up of ART and VMMC, as well as implementation of CCT for women aged 15–24 showed the greatest impact on reducing new HIV infections and AIDS-related deaths in Swaziland.

Disclosure of interest statement No conflicts of interest.