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DYSLIPIDEMIA AND ATHEROSCLEROSIS IN HIV INFECTION

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Premature atherosclerosis described in HIV-infected persons prior to introduction of HAART. ... of HIV and HAART on rates of sub-clinical atherosclerosis. ... – PowerPoint PPT presentation

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Title: DYSLIPIDEMIA AND ATHEROSCLEROSIS IN HIV INFECTION


1
DYSLIPIDEMIA AND ATHEROSCLEROSIS IN HIV INFECTION
  • MICHELLE FLORIS-MOORE, M.D., M.S.
  • AIDS Research Program
  • Dept. of Epidemiology Population Health
  • Montefiore Medical Center

2
BACKGROUND
  • Pre-HAART Era
  • HIV infection associated with high triglyceride
    and low HDL levels.
  • Premature atherosclerosis described in
    HIV-infected persons prior to introduction of
    HAART.
  • Autopsy studies found arteriopathy, with
    thickening of arterial intima and narrowing of
    the lumen.

3
HAART Era
  • Fat redistribution, with peripheral/facial
    wasting and central adiposity
  • May be predominantly LA or LH, or mixed LD
  • Lipoatrophy most strongly associated with NRTI
    use
  • Abnormal adipocytokine levels
  • Leptin variably related to LD.
  • Adiponectin levels lower in patients with LD.
    Some studies show stronger association with LA
    than with mixed LD.
  • Insulin resistance.
  • Increased LDL and triglycerides.

4
Leptin and Adiponectin
  • Leptin
  • secreted by adipocytes, also derived from other
    sources (e.g. skeletal muscle)
  • Regulates food intake and energy expenditure
  • deficiency ? insulin resistance
  • Adiponectin
  • Secreted exclusively by adipocytes
  • Decreased levels associated with insulin
    resistance, CVD.

5
HIV and Carotid IMT
  • Measured carotid IMT in Matched triads HIVve
    HIVve, PI-naïve HIVve, on PI.
  • Matched on age, race, gender, BP, smoking,
    menopausal status.
  • Excluded known CAD, DM, uncontrolled HTN, BMI gt
    30, fam h/o MI.
  • No differences in carotid IMT among groups.
    Traditional CAD risk factors assoc with ? IMT.

Currier J, et al (Abstract 131, CROI 2002)
6
  • Longitudinal study. HIVve vs HIV-ve. HIVves
    grouped by ART use.
  • Carotid IMT measured at baseline and 1 yr.
  • HIVve participants had
  • (1) higher baseline carotid IMT
  • (2) faster progression of IMT over 1 year
  • PI use not associated with IMT.

Hsue P, et al. Circulation 20041091603-1608
7
HIV and CAD outcomes
  • DAD study prospective multicenter study,
    23,468 participants.
  • ? total chol and TGs associated with length of
    exposure to ART.
  • 126 MIs (36 fatal) from 1999 2002.
  • Relative risk of MI 1.26 per year of HAART use.

Friis-Moller N, et al. AIDS 2003,
171179-1193 DAD Study Group. NEJM 2003, 349
1993-2003
8
HIV and CAD outcomes
  • Retrospective study of CAD events in 36,766 pts
    at VA hospitals, 1995-2001.
  • Median length of HAART rx 16 mths.
  • Outcome Hosp / death due to CAD / CVD.
  • CAD/CVD hosp rate ?d (1.7/100py to 0.9).
  • No association between ART and CAD/CVD.

Bozette S.A., et al. NEJM 2003 348702-710
9
Objectives
  • To describe the effect of HIV infection and
    HAART on the lipid profile.
  • To examine the relationship of HIV infection and
    HAART to body fat distribution and leptin and
    adiponectin levels.
  • To describe the effects of HIV and HAART on rates
    of sub-clinical atherosclerosis.

10
Study Population
  • Natural History of Menopause in HIV-Infected
    Drug Users (MS) study.
  • Ongoing 5-year longitudinal study of menopause in
    mid-life women who are either HIV-infected or at
    risk for HIV infection.
  • Women aged 35 or older who have not yet completed
    menopause transition.

11
Metabolic Sub-study
  • 240 women with no h/o MI
  • Recruited into 4 groups
  • HIV-uninfected
  • HIV-infected, ART-naive
  • HIV-infected, on non-PI HAART
  • HIV-infected, on PI-based HAART

12
Semi-annual Research Visit
  • Interview Medical history, medications, dietary
    intake, physical activity, drug and cigarette
    use.
  • Measurements Weight, height, BP, waist and hip
    circumference
  • Phlebotomy CD4 cell count, HIV Viral Load

13
Outcome Measures
  • Every 18 months, after a 12-hour overnight fast
    Total cholesterol, HDL-C, LDL-C, Triglycerides,
    Lipoprotein (a).
  • Fasting leptin, adiponectin, and FFA levels done
    at baseline.
  • DEXA scans done at 18 month intervals to evaluate
    body fat distribution.
  • Carotid artery ultrasound done to measure IMT at
    baseline and in Year 3.

14
Demographics
15
Drug Use
16
CD4 Count by ART group
p .40
17
HIV-Infected Participants
18
Duration of PI Use
19
BMI Distribution
kg/m2
p lt .001
20
Trunk and Limb Fat by HIV/ART Group
p .004
p .001
21
Trunk/Limb Fat Ratio by HIV/ART Group
p .15
22
Regional fat is lower in Cocaine UsersMS. n518


g/cm
g/cm
Trunk fat
Leg fat
23
Leptin by HIV/ART group
p .02
24
NHANES III Leptin Levels in Women by BMI and
Ethnicity
Ruhl CE, Everhart JE. Am J Clin Nutr
200174295-301.
25
Adiponectin by HIV/ART group
p .71
26
Factors Correlating with Leptin and Adiponectin
27
Lipids by HIV/ART group
p .052
Median TG
28
Lipids by CD4 Group
p lt .01
p .45
p .02
p .77
Median TG
29
Lipids CD4 gt 500 group compared to HIV -ves
p lt .01
p lt .01
p .47
Median TG
30
IGT and HTN by HIV/ART Group
p .68
p .34
Includes 15 women with pre-existing DM
31
Carotid Artery IMT
  • Common carotid artery IMT gt 0.8mm defined as
    abnormal thickness.
  • 15 randomly selected studies read by second
    radiologist for analysis of inter-rater
    reliability.
  • Intra-class Correlation Coefficient 0.99 (95
    CI 0.996 0.999)

32
Mean IMT (mm) by Gender
33
Percent with IMT gt 0.8mm by HIV/ART group
p .051
34
Multivariate Analysis of IMT
35
CONCLUSIONS
  • HIV-infected participants on HAART had lower
    trunk and limb fat mass compared to those not on
    ART and to HIV-uninfected participants.
  • Leptin levels correlated positively with trunk
    fat, limb fat, and HOMA-IR.
  • Adiponectin levels correlated negatively with
    trunk fat, trunk/limb fat ratio, and HOMA-IR, and
    positively with HDL levels.

36
CONCLUSIONS
  • Those in higher CD4 groups had higher levels of
    total cholesterol and LDL cholesterol.
  • Traditional risk factors (age, obesity) and
    current cocaine use were associated with
    increased risk of pre-clinical atherosclerosis.

37
ACKNOWLEDGEMENTS
  • MS Study
  • Ellie Schoenbaum
  • Julia Arnsten
  • Andrea Howard
  • Yungtai Lo
  • Nancy Budner
  • Galina Moskaleva
  • Mordecai Koenigsberg
  • Renee Shanker
  • Metta Cantlo
  • Madeline Crespo-Figueroa
  • Samantha Miller
  • Tufts Nutrition Collaborative - CDAAR
  • Alice Tang
  • Jane Lanzillotti
  • Lisa Gualtieri
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