IntroductionPeople living with HIV/AIDS (PLWHA) frequently struggle to maintain optimal adherence to antiretrovirals (ARVs). Different adherence-improving interventions have been developed and examined through decision analytic model-based health technology assessments. Therefore, we aimed to conduct a systematic review of all decision analytic models developed to improve adherence in PLWHA.MethodsThe review protocol was registered on Prospero (CRD42022270039) and relevant studies published from inception to 23 October 2022 were identified through searches of the following databases: PubMed, Embase, the National Health Service Economic Evaluation Database, PsycINFO, the Health Economic Evaluations Database, and EconLit. Studies were included if they were modeling works of full economic evaluations, including cost-effectiveness analyses (CEA), cost-utility analyses, cost-benefit analyses, and cost-consequence analyses. The primary outcome was the cost effectiveness of adherence interventions reported as the incremental cost per additional quality-adjusted life-year (QALY). Study quality was assessed with the Quality of Health Economics Studies instrument. Due to the heterogeneity of the data, a permutation matrix was used for quantitative data synthesis rather than a meta-analysis.ResultsThe 15 studies identified were conducted in North America (8/15), Africa (4/15), and Europe (3/15). The time horizon was one year in one study, ten years in one study, 20 years in three studies, and a lifetime horizon in ten studies. The types of interventions were smartphone-based (5/15), nurse involved (2/15), directly observed therapy (2/15), case manager involved (1/15), simplification of regimens (1/15), Link4Health (1/15), and others (3/15) that involved multicomponent intervention. The interventions gained higher QALYs with cost savings in all 15 studies and gained QALYs at a higher cost at an acceptable incremental cost-effectiveness ratio in 80 percent (12/15) of studies. The studies were of fair (13%) to high quality (87%).ConclusionsThis study is the first systematic review of decision analytic model-based CEAs of adherence interventions in the management of PLWHA. Most of the identified studies recently published good quality cost-effectiveness analyses with an adequate timeframe.