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Background: The aim of this review was to summarize the data on HIV/AIDS epidemiology and affected populations in Ghana and to describe the United States President's Emergency Plan for Emergency Relief's (PEPFAR) response to the epidemic., Design: We conducted a literature review focusing on PEPFAR's contribution to the HIV response in Ghana. Additionally, we summarized the epidemiology of HIV. We searched both peer-reviewed and grey literature., Setting: Ghana., Results: Overall, HIV prevalence in Ghana is 1.6% with regional variation. Key populations (KPs) are disproportionately affected by HIV in the country. FSW and their clients, and MSM, account for 28% of all new infections. PEPFAR provides technical assistance (TA) to Ghana to maximize the quality, coverage and impact of the national HIV/AIDS response. To ensure adequate supply of antiretrovirals (ARVs), in 2016-2017, PEPFAR invested $23.7 million as a onetime supplemental funding to support Ghana's ARV treatment program. In addition, the National AIDS Control Programme in collaboration with PEPFAR is implementing a scale up of viral load testing. PEPFAR is also implementing a comprehensive package of prevention services in five regions to help reach MSM and FSW and to expand HIV testing services for KPs., Conclusions: Ghana is making changes at both policy and program level in the fight against HIV/AIDS and is working towards achieving the UNAIDS' 90-90-90 targets. PEPFAR is providing TA to ensure these goals can be achieved., Funding: This manuscript has been supported by the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) through the Centers for Disease Control and Prevention (CDC)., Competing Interests: Conflict of interest: None declared