OBJECTIVES: Potential risk for diabetes among HIV patients using protease inhibitors (PIs) has been largely controversial in the literature. This systematic review and meta-analysis attempt to determine if PI use in treated HIV patients is associated with an increased risk of developing DM.

METHODS: A systematic literature search was performed using PubMed/Medline, EMBASE and Web of Science to retrieve observational studies published between January 1, 2000 and December 2018. Quality of cohort studies was assessed using the Newcastle-Ottawa Scale for cohort studies. Random-effects modelling was utilized to calculate pooled hazard ratios (HRs) and risk ratios (RRs). Possible heterogeneity was also assessed using Cochrane’s Q statistic from which the percentage of variation across studies (I²) was calculated. Publication bias was assessed using Begg and Mazumdar correlation rank test and visual inspection of asymmetry in the funnel plot. All analyses were conducted using Comprehensive Meta-analysis version 3.0.

RESULTS: Sixteen (16) cohort studies that met the quality criteria were included. Pooled RR based on the random effects model showed that use of PIs is associated with an increased risk of developing DM: (n=10; [RR: 1.25; 95 % CI: 1.07- 1.45]; p-value = 0.006, I²=57.0) while the pooled HR random effects model did not detect a significant association: (n=6; [HR: 1.16; 95 CI: 0.88 – 1.53]; p-value= 0.296, I2=39.9). There was no significant publication bias based on Begg’s test result: (p-value=0.5112).

CONCLUSIONS: This meta-analysis is currently the most comprehensive meta-analysis on the association between PI use and risk of DM. Results suggest that HIV patients taking PIs may have an increased risk of diabetes. More research using survival models is needed to better power the study to detect a possible association.