Background:  Abnormalities in glucose metabolism have been described with increasing frequency in patients with HIV and may result from both direct and indirect effects of highly active antiretroviral therapies (HAART). The incidence and prevalence of pre-diabetes and diabetes (DM) and their relationship to antiretroviral therapy has not been well defined in a prospective cohort.

Methods:  We examined the prevalence of hyperglycemia in 1107 men enrolled in the Multicenter AIDS Cohort Study, using data from April 1999 through September 2002. Hyperglycemia (pre-diabetes and DM) was defined as a fasting plasma glucose (FPG) ³110 mg/dL, use of anti-diabetic medication, or self-reported diagnosis of DM. DM was defined as a FPG ³126 mg/dL, use of anti-diabetic medication, or self-reported diagnosis of DM. Of the 1107 men, 563 were HIV^- and 544 were HIV⁺ (423 on HAART). For the 618 men with a FPG £105 mg/dL, no history of DM or use of anti-diabetic medication at baseline, the incidence rates of hyperglycemia and DM were determined. In addition, we examined the association between incident pre-diabetes and DM, and specific anti-retroviral regimens, including the use of protease inhibitors (PI), d4T, and efavirenz. 

Results:  Of HIV⁺ men on HAART, 14% had prevalent DM at baseline compared with 5% in the HIV^- group (odds ratio = 4.4; 95% confidence interval [CI]: 2.6, 7.4, after adjustment for age and body mass index [BMI]). Of 618 men, 79 (13%) incurred incident hyperglycemia in 1054 person-years yielding an overall rate of 7.5 cases per 100 person-years (95% CI:  6.0, 9.4), and 38 incurred incident DM in 1088 person-years, yielding an overall rate of 3.5 cases per 100 person-years (95% CI:  1.7, 3.7). After adjustment for age and BMI, the hazard of pre-diabetes or DM among the HIV⁺ HAART group was 1.8 times (95% CI: 1.1, 3.0) that of the HIV^- group, and the hazard of DM among the HIV⁺ HAART group was 3.1 times (95% CI: 1.3, 7.1) that of the HIV^- group. Exposure to a HAART regimen including a PI (hazard ratio [HR] = 1.9; 95% CI:  1.1, 3.3), d4T (HR = 2.1; 95% CI:  1.1, 3.9) or efavirenz (HR = 3.9; 95% CI:  1.6, 9.5) were each significantly associated with a higher rate of incident pre-diabetes or DM compared to the HIV^- group.

Conclusions:  HIV⁺ men with HAART exposure have an increased prevalence and incidence of pre-diabetes and DM. Exposure to a HAART regimen—including PIs, d4T, or efavirenz—was associated with an apparent increased risk of hyperglycemia.

Keywords: diabetes; antiretrovirals; metabolic complications