indinavir-sulfate and Diabetes-Mellitus

To evaluate the incidence and determinants of diabetes in a cohort of HIV-infected adults initiated with combination antiretroviral treatment (cART) in 1997-1999 and followed up to 2009.. Prospective study of 1046 patients at 47 French clinical sites.. Potential determinants of diabetes occurrence, defined by confirmed increased glycemia and/or initiation of antidiabetic treatment, were assessed by a proportional hazards model, including time-updated metabolic parameters and ART exposure.. Among the cohort, representing 7846 person-years of follow-up (PYFU), 54% received indinavir, 75% stavudine and 52% didanosine. Overall, 111 patients developed diabetes, with an incidence of 14.1/1000 PYFU (14.6 in men, 12.6 in women). Incidence peaked in 1999-2000 (23.2/1000 PYFU) and decreased thereafter. The incidence of diabetes was associated [adjusted hazard ratio (aHR), all P<0.02] with older age (hazard ratio = 2.13 when 40-49 years, hazard ratio = 3.63 when ≥50 years), overweight (hazard ratio = 1.91 for a BMI 25-29 kg/m(2), hazard ratio = 2.85 >30 kg/m(2)), waist-to-hip ratio (hazard ratio = 3.87 for ≥0.97 male/0.92 female), time-updated lipoatrophy (hazard ratio = 2.14) and short-term exposure to indinavir (0-1 year: hazard ratio = 2.53), stavudine (0-1 year: hazard ratio = 2.56, 1-2 years: hazard ratio = 2.65) or didanosine (2-3 years: hazard ratio = 3.16). Occurrence of diabetes was not associated with HIV-related markers, hepatitis C, hypertension or family history of diabetes. Insulin resistance was predictive for incident diabetes.. In this nationwide cohort, followed for 10 years after cART initiation, diabetes incidence peaked in 1990-2000, was markedly higher than that reported for European uninfected or other HIV-infected populations (4-6/1000 PYFU) and linked with age and adiposity. Adiposity and glycemic markers should be monitored in aging HIV-infected patients.

Topics: Adiposity; Adult; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Body Mass Index; Cohort Studies; Diabetes Mellitus; Didanosine; Female; Follow-Up Studies; HIV Infections; Humans; Incidence; Indinavir; Male; Middle Aged; Odds Ratio; Proportional Hazards Models; Prospective Studies; Risk Factors; Stavudine; Waist-Hip Ratio

In a nationwide, population-based cohort study we assessed the risk of diabetes mellitus (DM) in HIV-infected individuals compared with the general population, and evaluated the impact of risk factors for DM in HIV-infected individuals.. We identified 4,984 Danish-born HIV-infected individuals from the Danish HIV Cohort Study and a Danish born population-based age- and gender-matched comparison cohort of 19,936 individuals (study period: 1996-2009). Data on DM was obtained from the Danish National Hospital Registry and the Danish National Prescription Registry. Incidence rate ratios (IRR) and impact of risk factors including exposure to Highly Active Antiretroviral Therapy (HAART) and antiretroviral drugs were estimated by Poisson regression analyses.. In the period 1996-1999 risk of DM was higher in HIV-infected individuals compared to the comparison cohort (adjusted IRR: 2.83; 95%CI: 1.57-5.09), both before (adjusted IRR: 2.40; 95%CI: 1.03-5.62) and after HAART initiation (adjusted IRR: 3.24; 95% CI: 1.42-7.39). In the period 1999-2010 the risk of DM in HIV-infected individuals did not differ from that of the comparison cohort (adjusted IRR: 0.90; 95% CI: 0.72-1.13), although the risk was decreased before HAART-initiation (adjusted IRR: 0.45; 95%CI: 0.21-0.96). Increasing age, BMI and the presence of lipoatrophy increased the risk of DM, as did exposure to indinavir, saquinavir, stavudine and didanosine.. Native HIV-infected individuals do not have an increased risk of developing DM compared to a native background population after year 1998. Some antiretroviral drugs, not used in modern antiretroviral treatment, seem to increase the risk of DM.

Topics: Adult; Anti-Retroviral Agents; Antiretroviral Therapy, Highly Active; Body Mass Index; Cohort Studies; Denmark; Diabetes Complications; Diabetes Mellitus; Didanosine; Female; HIV Infections; Humans; Incidence; Indinavir; Male; Middle Aged; Regression Analysis; Risk Factors; Saquinavir; Stavudine; Treatment Outcome

Topics: Adult; Diabetes Mellitus; HIV Infections; HIV Protease Inhibitors; Humans; Indinavir; Male; Nelfinavir

Topics: Adult; Anti-HIV Agents; Diabetes Mellitus; Diagnosis, Differential; HIV Infections; Humans; Indinavir; Male

To describe a syndrome of peripheral lipodystrophy (fat wasting of the face, limbs and upper trunk), hyperlipidaemia and insulin resistance in patients receiving potent HIV protease inhibitor therapy.. Cross-sectional study.. Outpatient clinic of a university teaching hospital.. HIV-infected patients either receiving at least one protease inhibitor (n=116) or protease inhibitor-naive (n=32), and healthy men (n=47).. Lipodystrophy was assessed by physical examination and questionnaire and body composition by dual-energy X-ray absorptiometry. Fasting triglyceride, cholesterol, free fatty acid, glucose, insulin, C-peptide and fructosamine levels, other metabolic parameters, CD4 lymphocyte counts, and HIV RNA load were also assessed.. HIV protease inhibitor-naive patients had similar body composition to healthy men. HIV protease inhibitor therapy was associated with substantially lower total body fat (13.2 versus 18.7 kg in protease inhibitor-naive patients; P=0.005), and significantly higher total cholesterol and triglyceride levels. Lipodystrophy was observed clinically in 74 (64%) protease inhibitor recipients after a mean 13.9 months and 1(3%) protease inhibitor-naive patient (P=0.0001). Fat loss occurred in all regions except the abdomen after a median 10 months. Patients with lipodystrophy experienced a relative weight loss of 0.5 kg per month and had significantly higher triglyceride, cholesterol, insulin and C-peptide levels and were more insulin-resistant than protease inhibitor recipients without lipodystrophy. Patients receiving ritonavir and saquinavir in combination had significantly lower body fat, higher lipids and shorter time to lipodystrophy than patients receiving indinavir. Three (2%) patients developed new or worsening diabetes mellitus.. A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance is a common complication of HIV protease inhibitors. Diabetes mellitus is relatively uncommon.

Topics: Adult; Anti-HIV Agents; Body Composition; Cross-Sectional Studies; Diabetes Mellitus; Female; HIV Infections; HIV Protease Inhibitors; Humans; Hyperlipidemias; Indinavir; Insulin Resistance; Lipodystrophy; Male; Nelfinavir; Risk Factors; Ritonavir; Saquinavir; Syndrome

Topics: Diabetes Complications; Diabetes Mellitus; HIV Infections; HIV Protease Inhibitors; Humans; Hyperglycemia; Indinavir; Nelfinavir; Ritonavir; Saquinavir