BACKGROUNDThe Chronic Care Model is an effective framework for improving chronic disease management. There is scarce literature describing this model for people living with HIV. Decision Support (DS) and Clinical Information Systems (CIS) are two components of this model that aim to improve care by changing health care provider behavior.OBJECTIVEOur aim was to assess the effectiveness of DS and CIS interventions for individuals with HIV, through a systematic literature review.DESIGNWe performed systematic electronic searches from 1996 to February 2011 of the medical (E.g. Medline, EMBASE, CINAHL) and grey literature. Effectiveness was measured by the frequency of statistically significant outcome improvement. Data and key equity indicator extraction and synthesis was completed.PARTICIPANTS AND INTERVENTIONSWe included comparative studies of people living with HIV that examined the impact of DS or CIS interventions on outcomes.MAIN MEASURESThe following measures were assessed: outcome (immunological/virological, medical, psychosocial, economic measures) and health care process/performance measures.KEY RESULTSRecords were screened for relevance (n = 10,169), full-text copies of relevant studies were obtained (n = 123), and 16 studies were included in the review. Overall, 5/9 (55.6%) and 17/41 (41.5%) process measures and 5/12 (41.7%) and 3/9 (33.3%) outcome measures for DS and CIS interventions, respectively, were statistically significantly improved. DS–explicit mention of implementation of guidelines and CIS-reminders showed the most frequent improvement in outcomes. DS-only interventions were more effective than CIS-only interventions in improving both process and outcome measures. Clinical, statistical and methodological heterogeneity among studies precluded meta-analysis. Primary studies were methodologically weak and often included multifaceted interventions that made assessment of effectiveness challenging.CONCLUSIONSOverall, DS and CIS interventions may modestly improve care for people living with HIV, having a greater impact on process measures compared to outcome measures. These interventions should be considered as part of strategies to improve HIV care through changing provider performance.Electronic supplementary materialThe online version of this article (doi:10.1007/s11606-012-2145-y) contains supplementary material, which is available to authorized users.