Management of LongTerm Metabolic Complications: CaseBased Discussion

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Management of Long-Term Metabolic Complications
Case-Based Discussion
Oluwatoyin Adeyemi, MDAssistant Professor of
MedicineRush Medical College
The International AIDS SocietyUSA
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Statins and CVS risk

• Statins are the agents of choice for 1º and 2º
  cardiovascular prevention achieving a 20
  reduction in MM by lowering LDLc by 1mmol/L
  (meta-analysis of 90,000 HIV- pts).
• Have pleiotropic effects- effect on SREBP,
  favorable efects on inflammation, endothelium and
  coagulation cascade.
• Pravastatin, fluvastatin and rosuvastatin not
  metabolized through CYP-3A4.

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Dyslipidemia Lipid-Lowering Therapy vs PI to
NNRTI Switch
Calza L, et al. AIDS. 2005191051-1058.
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Relationship Between Myocardial Infarction and
HAART
RR 1 1.8 1.9 2.3
3.1 3.2 3.1 4.4
RR per year of cART Overall 1.17 Men 1.14 Women
1.38
El-Sadr W, et al. 12th CROI. 2005. Abstract 745.
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Risk Factors for Myocardial Infarction in DAD
El-Sadr W, et al. 12th CROI. 2005. Abstract 745.
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Prevalence of CVD Risk Factors in DAD Cohort
Friis-Moller N, et al. AIDS. 2003171179-1193.
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Contribution of Dyslipidemia to Myocardial
Infarction Risk
El-Sadr W, et al. 12th CROI. 2005. Abstract 745.
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Cardiovascular Risk Factors Increased with Time
On HAART
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MI Risk Factors in HIV-Positive Patients

• 2115 patients (9.0) at high risk for MI over 10
  years
• Reclassifying smokers as nonsmokers reduced total
  high-risk proportion from 9.0 to 4.1
• Assuming lower cholesterol levels decreased total
  proportion from 9.0 to 5.8

All data adjusted according to country, with
patients with previous cardiovascular disease
assumed to have 5-fold greater risk of MI.
Law M, HIV Med 20067218-230
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Studies examining relationship b/w use of HAART,
HIV infection and risk of CVS
Increase CV events
Grinspoon sk. AIDS 2005 19 641-652
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Interventions for Insulin Resistance

• Diet No randomized study
• Metformin and exercise1
• Both improve insulin resistance, blood pressure,
  waisthip ratio
• Reduce visceral fat, but also reduce subcutaneous
  fat
• Do not appear to alter lipids
• Rosiglitazone2,3
• Improves insulin resistance
• Worsens LDL-C and triglycerides
• No benefit for lipoatrophy

1. Driscoll, et al. AIDS. 200418465-473. 2.
Carr, et al. Lancet. 2004363429-438. 3.
Hadigan, et al. Ann Intern Med. 2004140786-794.
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Treatment Interventions for Lipoatrophy Previous
Studies
1. Carr A, et al. JAMA. 2002288207-215. 2.
Martin A, et al. AIDS. 2004181029-1036. 3.
McComsey G, et al. Clin Infect Dis.
200438263-270. 4. Moyle G, et al. CROI 2005.
Abstract 44LB. 5. Milinkovic A, et al. CROI
2005. Abstract 857. 6. Murphy R, et al. CROI
2005. Abstract 45LB. 7. Sutinen J , et al 7th
Lipo Workshop. Abstract. 8. Mallon P, et al.
AIDS. In press. 9. Sutinen J, et al. Antiviral
Ther. 20038199-207. 10. Carr A, et al. Lancet.
2004363429-438. 11. Hadigen C, et al. Ann
Intern Med. 2004140786-794. 12. Cavalcanti R,
et al. CROI 2005. Abstract 854.
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Treatment Interventions for LipoatrophyNew
Studies
1. Slama L, et al. CROI 2006. Abstract 151LB. 2.
Kohli R, et al. CROI 2006. Abstract 148. 3.
Mulligan K, et al. CROI 2006. Abstract 147. 4.
Shikuma C, et al. CROI 2006. Abstract 149.
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Stavudine to Tenofovir switch- The Lipo-Rec
study group

• 873 HIVpts (352 in the lipid sub-study)
• Stavudine for median of 4 yrs, 73 on NNRTI
  regimen, 77 with lipodystrophy (86 of these
  lipoatrophy), 12 on lipid lowering meds.
• TFV substituted for stavudine (77 lipodystrophy,
  13 neuropathy, 26 lipids, 10 high TG).
• At wk 48- sustained reduction in TC (-17.5mg/dl),
  LDL-c (-8.1) and TG (-35), greatest in pts with
  baseline hyperlipidemia (-29 LDL-c and 76 TG)
  respectively.
• Greatest TG decrease in pts with TGgt500 (-266)
• 10yr CVR decreased in all pts (plt0.001)

Llibre et al. AIDS 20061407-1414