Esteban Mart nez Hospital Cl nic University of Barcelona Frascati, 15 July 2011

1. Esteban Martínez Hospital Clínic & University of Barcelona Frascati, 15 July 2011

2. Metabolic problems in HIV+ patients Stroke and metabolic problems Neurocognitive impairment and metabolic problems

3. Metabolic problems in HIV+ patients Stroke and metabolic problems Neurocognitive impairment and metabolic problems

6. El descenso del HDL-colesterol tiene un papel muy importante en el riesgo de enfermedad coronaria. Su papel supera, incluso, al papel protector que puede tener un nivel plasmatico bajo de LDL-colesterol. Como se puede ver en esta diapositiva del Estudio Framingham, para cualquier nivel de LDL-colesterol que se considere, el nivel de HDL-colesterol modula de forma importante el riesgo cardiovascular. De este modo, si una persona tiene un nivel elevado de LDL-colesterol como 220 mg/dL pero su HDL-colesterol esta tambien elevado (85 mg/dL), el riesgo de enfermedad coronaria es muy bajo. Por contra, si una persona tiene una LDL-colesterol optimo (100 mg/dL) pero su HDL-colesterol es bajo (25 mg/dL) su riesgo de enfermedad coronaria es mas del doble que en el ejemplo previo.El descenso del HDL-colesterol tiene un papel muy importante en el riesgo de enfermedad coronaria. Su papel supera, incluso, al papel protector que puede tener un nivel plasmatico bajo de LDL-colesterol. Como se puede ver en esta diapositiva del Estudio Framingham, para cualquier nivel de LDL-colesterol que se considere, el nivel de HDL-colesterol modula de forma importante el riesgo cardiovascular. De este modo, si una persona tiene un nivel elevado de LDL-colesterol como 220 mg/dL pero su HDL-colesterol esta tambien elevado (85 mg/dL), el riesgo de enfermedad coronaria es muy bajo. Por contra, si una persona tiene una LDL-colesterol optimo (100 mg/dL) pero su HDL-colesterol es bajo (25 mg/dL) su riesgo de enfermedad coronaria es mas del doble que en el ejemplo previo.

12. Speaking points: A substudy of the Multicenter AIDS Cohort Study (MACS) compared the prevalence and incidence of diabetes mellitus (DM) 229 HIV-infected men on HAART and 361 uninfected control subjects, over a 3 year observation period, with median follow-up of 2.3 years At baseline, subjects included in the sub study had a fasting glucose of =98 mg/dL, no self-report of DM or use of antidiabetic medication Incidence of DM, which was defined as fasting glucose =126 mg/dL, self-report of DM or use of antidiabetic medication, was higher in the HIV-infected subjects as compared to the uninfected controls (RR=4.11; 95% CI, 1.85-9.16) The rate of incident DM was 4.7 per 100 person years among HIV-infected men using HAART compared with 1.4 cases per 100 person years among HIV-seronegative men Reference: Brown TT, et al. Arch Int Med. 2005;165:1179-1184. Speaking points: A substudy of the Multicenter AIDS Cohort Study (MACS) compared the prevalence and incidence of diabetes mellitus (DM) 229 HIV-infected men on HAART and 361 uninfected control subjects, over a 3 year observation period, with median follow-up of 2.3 years At baseline, subjects included in the sub study had a fasting glucose of =98 mg/dL, no self-report of DM or use of antidiabetic medication Incidence of DM, which was defined as fasting glucose =126 mg/dL, self-report of DM or use of antidiabetic medication, was higher in the HIV-infected subjects as compared to the uninfected controls (RR=4.11; 95% CI, 1.85-9.16) The rate of incident DM was 4.7 per 100 person years among HIV-infected men using HAART compared with 1.4 cases per 100 person years among HIV-seronegative men Reference: Brown TT, et al. Arch Int Med. 2005;165:1179-1184.

13. HIV* men more likely to have metabolic syndrome than HIV- men ?HDL, ?TGs, ?glucose more likely in HIV+ ?waist circumference less likely in HIV+ The Multicenter AIDS Cohort Study (MACS) has followed a group of HIV-positive and HIV-negative men who have sex with men (MSM) across the United States for almost 20 years. This study evaluated the prevalence of metabolic syndrome in 646 HIV-positive men and 397 HIV-negative men in the MACS cohort. HIV-positive men were more likely than HIV-negative men to have evidence of the metabolic syndrome. Furthermore, HIV-positive men were more likely to have elevated fasting triglycerides, elevated fasting glucose, and low HDL cholesterol—some of the parameters used to make a diagnosis of the metabolic syndrome. The metabolic syndrome is tightly linked to increases in risk for cardiovascular events in the general population. For more information, please go online to: http://www.clinicaloptions.com/hiv/conf/rio2005/cs/TuPe2.2B18.asp The Multicenter AIDS Cohort Study (MACS) has followed a group of HIV-positive and HIV-negative men who have sex with men (MSM) across the United States for almost 20 years. This study evaluated the prevalence of metabolic syndrome in 646 HIV-positive men and 397 HIV-negative men in the MACS cohort. HIV-positive men were more likely than HIV-negative men to have evidence of the metabolic syndrome. Furthermore, HIV-positive men were more likely to have elevated fasting triglycerides, elevated fasting glucose, and low HDL cholesterol—some of the parameters used to make a diagnosis of the metabolic syndrome. The metabolic syndrome is tightly linked to increases in risk for cardiovascular events in the general population. For more information, please go online to: http://www.clinicaloptions.com/hiv/conf/rio2005/cs/TuPe2.2B18.asp

14. Metabolic problems in HIV+ patients Stroke and metabolic problems Neurocognitive impairment and metabolic problems

19. Metabolic problems in HIV+ patients Stroke and metabolic problems Neurocognitive impairment and metabolic problems

21. Cross-sectional study 98 patients, 44 years, 63% previous AIDS 24% had CV risk (diabetes, hypertension, or both) 6 neurocognitive domains assessed After adjusting for age, CV risk was associated with: Slower processing speed (P=0.4) Poorer verbal fluency (P=0.002) Compared with CV risk-treated patients, patients with untreated CV risk had: Reduced processing speed, learning/memory, and executive functioning

23. SMART sub-study 292 participants from Australia, North America, Brazil, and Thailand 536 median CD4 cells/mm3, 88% HIV-1 RNA <400 c/mL 5-test neurocognitive battery 14% had neurocognitive impairment (NCI). Prior CVD was associated with NCI Prior CVD, hypercholesterolemia, and hypertension were associated with poorer neurocognitive performance HIV (CD4 cells or HIV-1 RNA) or ART (CNS penetration effectiveness rank) were not associated with poorer neurocognitive performance

25. ? HDL cholesterol is the characteristic lipid problem in HIV+ patients. ? TGs may occur in association with RTV-boosted PIs and lipodystrophy. ? total body fat and ?limb fat are the characteristic fat problems in HIV+ patients. There is a relative ? in VAT. Diabetes mellitus and metabolic syndrome occur at a higher risk in HIV+ patients Ischemic stroke is associated with HIV factors rather than with CV factors Neurocognitive impairment is associated with CV factors rather than with HIV factors