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Antiretroviral therapy (ART) has transformed HIV infection from a death sentence into a chronic condition. In sub-Saharan Africa, the area most affected by this disease, availability of ART has increased dramatically over the last few years. Nevertheless, many people are still not receiving ART either because they are not aware of being HIV-positive or because they struggle to access ART or to engage in HIV care. It is fundamental to take decisions which maximise the health benefits with the limited resources available. When I was writing this thesis, there were countless discussions regarding whether the recommendation on when to start ART had to be modified to a CD4 count threshold higher than 350 cells/μL, given the compelling evidence that ART reduces substantially the risk of transmission in heterosexual serodifferent couples. In this thesis I evaluated the effectiveness and cost-effectiveness of alternative ways of increasing the number of adults receiving ART in South Africa: increasing the CD4 count threshold at which a person is eligible to be initiated on ART, or maintaining the eligibility criteria to CD4 count below 350 cells/μL but expanding the number of people who are diagnosed and engaged in care. In particular, I focused on the impact these two alternatives would have on the development and transmission of resistance. To inform the model on the extent to which NNRTI resistance mutations are present in people who have interrupted NNRTI, I conducted an analysis using data from the UK resistance database. In addition, since I found that the most cost-effective strategy was to expand the number of people engaged in HIV care without modifying the CD4 threshold at which a person is eligible to receive ART, I evaluated at which steps in the current leaky cascade of HIV care it was most cost-effective to intervene. Finally, as new evidence regarding the accuracy and acceptability of HIV self-testing came up, I decided to evaluate the cost-effectiveness of introducing HIV self-testing in a setting such as Zimbabwe.