Advances in biomedical technologies provide potential for adolescent HIV prevention and HIV-positive survival. The UNAIDS 90–90–90 treatment targets provide a new roadmap for ending the HIV epidemic, principally through antiretroviral treatment, HIV testing and viral suppression among people with HIV. However, while imperative, HIV treatment and testing will not be sufficient to address the epidemic among adolescents in Southern and Eastern Africa. In particular, use of condoms and adherence to antiretroviral therapy (ART) remain haphazard, with evidence that social and structural deprivation is negatively impacting adolescents’ capacity to protect themselves and others. This paper examines the evidence for and potential of interventions addressing these structural deprivations.