A total of 28 peer-reviewed publications and a book chapter forms the basis of this PhD thesis, which reports on original contributions to scientific knowledge and impact over the past 15 years to the HIV response in Botswana and Zimbabwe. The peer reviewed publications included herein represent a portion of the more extensive research portfolio of the author on aligned topics. The aspects which are included in each of the thesis chapters are summarised below. Table 1, at the end of this section, includes key details of each of the publications included in this thesis. The commentary section of this thesis summarises the contribution in HIV prevention, care, treatment, and risk mitigation arenas, and how these enabled both Botswana and Zimbabwe to have robust HIV responses, which have been commended for sustained interventions that enabled progress toward epidemic control in southern Africa. The population groups at the greatest risk of HIV acquisition in Botswana and Zimbabwe are presented and interventions proffered. The governance and partnerships required for a successful HIV response and the need for a robust health system to support any effective HIV programme is explained. The impact of COVID-19 on the otherwise successful and mature HIV response, as well as providing recommendations for effective COVID-19 pandemic responses in the context of an existing HIV epidemic is presented in the commentary. Finally, the thesis presents lessons learned and how these can be applied within the boundaries of Botswana and Zimbabwe but also around the globe, it also proffers recommendations and outlines further key areas for investigation.