Background: Hyperglycemia has been reported frequently both among HIV-infected patients receiving protease inhibitors (PIs) and HCV-infected persons. However, little is known about the relationship of HCV and diabetes mellitus (DM) in HIV-infected persons receiving highly active antiretroviral therapy (HAART).

Methods: We conducted a cross-sectional study (n=3157) to assess the relationship between HCV and diabetes and a prospective study (n=983 persons on HAART with at least 2 pretreatment nonfasting glucose measurements <200 mg/dL) to ascertain the incidence of diabetes among persons receiving HAART in a university-based, urban HIV clinic.  Incident and prevalent DM were defined as nonfasting glucose >200 mg/dL.  Cox proportional hazards regression was used to identify risk factors of diabetes.

Results: The prevalence of DM was higher in HCV-infected persons (278/1442; 19.3%) than HCV-uninfected persons (241/1715; 14.1%) (p<0.0001) even after adjustment for age, gender, race, and weight (odds ratio, 1.4; 95% confidence interval [CI], 1.2-1.7). Among HAART recipients, the incidence of DM per 100 person-years was 7.2 (95% CI, 6.2-8.3) overall, 8.2 (95% CI, 6.7-10.1) for HCV-infected persons and 6.3 (95% CI, 5.0-7.8) for HCV-uninfected persons.  The incidence of DM per 100 person-years on specific drug regimens was: ritonavir (8.5; 95% CI, 6.1-11.7), indinavir (7.4; 95% CI, 5.1-10.6), nelfinavir (7.3; 95% CI, 5.2-10.0), saquinavir (7.1; 95% CI 4.9-10.3), efavirenz (7.7; 95% CI, 5.3-11.2), and nevirapine (4.2, 95% CI, 2.4-7.5).  Older age, pretreatment CD4 count < 200 cells/mm³, and failure to increase at least 50 CD4 cells/mm³ during treatment were independent risk factors for DM.  The risk of DM among ritonavir users was significantly higher than nevirapine users (RH, 2.0; 95% CI, 1.1-4.0) but no other significant differences between drugs were detected.  Of note, 25% of DM cases occurred in young persons (< 40 years) weighing <150 pounds.

Conclusions: DM is marginally more common in HCV/HIV co-infected patients, but HCV did not substantially increase the risk of incident DM in persons receiving HAART.  In addition, although incident DM appears to be common during HAART, particularly among patients without traditional risk factors for diabetes (e.g., older age and obesity), the incidence rate of DM was similar for all PIs and efavirenz, suggesting that factors other than PI use may contribute to the pathogenesis of DM in HIV-infected persons.