The association between HIV, antiretroviral therapy, and gestational diabetes mellitus

Objectives: The widespread, chronic use of antiretroviral therapy raises questions concerning the metabolic consequences of HIV infection and treatment. Antiretroviral therapy, and specifically protease inhibitors, has been associated with hyperglycemia. As pregnant women are vulnerable to development of hyperglycemia, the objective of this study was to explore existing literature on the relationship between HIV infection, HIV treatment, and gestational diabetes mellitus (GDM). Methods: A systematic search was conducted in six databases for articles providing data on HIV-positivity, protease inhibitor exposure, and GDM or glucose intolerance development in pregnancy. The quality of articles was evaluated using an adapted Cochrane Collaboration bias assessment tool. Risk ratios were generated from pooled data using meta-analysis by the Mantel-Haenszel method. Results: Of 891 references screened, six studies on the role of HIV-positivity, 10 on protease inhibitor use, and two on both were included. Meta-analysis showed no significant relationship between HIV infection and the development of GDM [risk ratio 0.80, 95% confidence interval (CI): 0.47-1.37, I20%]. Meta-analysis of protease inhibitor exposure showed increased GDM in studies using first-generation protease inhibitors (risk ratio 2.29, 95% CI: 1.46-3.58) and studies using the strictest diagnosis criteria, the National Diabetes Data Group criteria for 3-h oral glucose tolerance test (risk ratio 3.81, 95% CI: 2.18-6.67). Conclusion: Meta-analysis showed no significant association between HIV-positivity and GDM. Significance of protease inhibitor use was limited to studies using the strictest diagnostic criteria for GDM. Results are limited by high risk of bias. Well designed prospective studies are needed to further clarify this relationship and its consequences for clinical practice.