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Background: Despite past and present global interventions, the human immunodeficiency virus (HIV) pandemic remains a public health problem in low- and middle-income countries (LMICs). The World Health Organization (WHO) has assisted these countries by providing antiretroviral therapy (ART) policies for adoption and adaptation to local needs. Objectives: This article describes the response of countries in sub-Saharan Africa (SSA), to the WHO’s changing CD4-threshold ART-initiation recommendations of the past two decades. Methods: Relevant articles published in international peer-reviewed journals were accessed via the following search engines: PubMed, Google Scholar, Cochrane, Embase and EBSCOhost. The study’s inclusion criteria were articles published in the English language between 2000 and 2019 that highlighted changes to the CD4 ART-initiation threshold and that focused on the WHO’s ‘commencement of ART’ policy guidelines. Sixteen studies (n = 16) from SSA were identified and included in this review: four are cross-sectional, four deal with cost-effectiveness, four are retrospective, one is a randomised trial and three are observational studies. Only studies conducted in SSA were assessed. Results: Four themes emerged: (1) adoption of the WHO CD4-ART-initiation policy by SSA countries, (2) timely implementation of the changing guideline initiation policy in the region, (3) barriers and facilitators encountered in the implementation of the changing guidelines and (4) description of similarities in policy implementation at country level from 2002 to 2019. Regional studies – cross-sectional, observational, retrospective, cost-effectiveness and randomised have described greater access to ART in SSA. However, barriers remain. The most common barriers to the timely implementation of ‘new’ ART-initiation guidelines were economic constraints, drug stock-outs, delays in obtaining baseline blood-test results and staff shortages. Conclusion: Although countries in SSA have adopted the WHO-ART-CD4 initiation-threshold policy guidelines, implementation has seldom occurred in a timely manner. Barriers have been identified. Whilst a small number of countries have implemented recommendations promptly, for many, the barriers still require to be overcome.