Background Young males (YMs) and especially young females (YFs) (age 15–24) in sub-Saharan Africa are at a higher risk of HIV infection compared to older adults. HIV testing of young individuals facilitates early identification of their ‘HIV+’ status, prompt ART initiation, and provision of male circumcision and PrEP. We hypothesise that youth-prioritised combination interventions could have substantial impact on HIV incidence among them and the wider adult population.

Methods We constructed a mathematical model that represented HIV heterosexual transmission in Nyanza, Kenya and used local data to specify cross-generational sex, risk- and age-dependent behaviours, and school attendance. We estimated the impact of leveraging HIV testing and counselling for condom use among Nyanza youth, prompt ART initiation (at CD4≤ 350 cells/mm³) for those newly-found infected, and gender-specific interventions for YMs and YFs. The former reaching 80% circumcision among ‘HIV-‘ YMs while the later reaching 40% PrEP coverage among ‘HIV-‘ YFs not attending school and halving the proportion of partnerships that YFs attending school form with 20+ years-old men.

Results We predict a reduction in HIV incidence over 10 years among youth by 38% (from 1.6%/person-years) and adults by 29% (from 1.2%/person-years), if the annual testing likelihood for youth increases to 90% with those newly-found infected increasing condom use by 30% and initiating ART promptly. The adult incidence is reduced 34% and 35% by further male and female specific interventions when applied separately. The full package with all interventions combined would decrease incidence among youth and adults by 59% and 40%, respectively, and reduce the lifetime HIV risk experienced by YFs by 24%.

Conclusion In populations where young people are at the highest risk of HIV infection, carefully prioritised, gender-specific intervention can have a substantial impact on the risk of infection, both in that group and the overall population.