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HIV treatment requires lifelong adherence to medication regimens that comprise inconvenient scheduling, adverse side effects, and lifestyle changes. Antiretroviral adherence and treatment fatigue have been inextricably linked. Adherence in HIV-infected populations has been well investigated; however, little is known about treatment fatigue. This review examines the current state of the literature on treatment fatigue among HIV populations and provides an overview of its etiology and potential consequences. Standard systematic research methods were used to gather published papers on treatment fatigue and HIV. Five databases were searched using PRISMA criteria. Of 1557 studies identified, 21 met the following inclusion criteria: (a) study participants were HIV-infected; (b) participants were prescribed antiretroviral medication; (c) the article referenced treatment fatigue; (d) the article was published in a peer …