Decentralization of HIV care to get treatment closer to where people live is essential to achieve the UNAIDS target of ensuring 90% of HIV positive individuals know their status, 90% of diagnosed HIV positive individuals receive sustained antiretroviral therapy (ART) and 90% of people on ART have suppressed viral load (90-90-90) by 2020. However, decentralization of antiretroviral treatment in resource limited settings is often inequitable between rural and urban settings, due to severe shortages of health workers in rural settings, even where task-shifting to lower cadres for delivery of ART is undertaken, as recommended by WHO. The results of the four studies discussed in this PhD thesis are nested within two multi-country projects conducted by the Joint Clinical Research Centre (JCRC) based in Kampala, Uganda. The first project, the Lablite Project (Optimizing Clinical Care Strategies and Laboratory Monitoring for Cost-effective Roll-Out of Antiretroviral Therapy in Africa) was an implementation project conducted in Malawi, Uganda and Zimbabwe. The second project was a clinical trial; the pediatric HIV CHAPAS-3 trial (Pharmacokinetics and Adherence/Acceptability of Simple Antiretroviral Regimens) conducted in Uganda and Zambia. The overall goal of the studies conducted in Eastern and Southern African region was to describe and understand roll out and uptake of antiretroviral therapy services to lower level health facilities in resource limited settings. In summary our studies showed, ART coverage and HIV testing increased after decentralization of ART at local health facility at population level. At patient level, we found that bringing ART closer to patients’ homes improves ease of access through reductions in distance to the facility, travel time, and out of pocket expenses. Cost effective models of community level access to ART that aim to minimize distance and patient related costs in accessing ART should be studied further. Lastly we observed high levels of adherence to ART, particularly among children whose caregiver’s beliefs in necessity of treatment most strongly outweighed their concern. We showed that a beliefs in medicine questionnaire (BMQ) is a valuable screening tool to help at the primary healthcare level to identify caregivers who may benefit from a more intensive follow up.