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HIV Lipodystrophy
Jisun OhPGY-2 Internal Medicine
University of Western OntarioEndocrinology Half Day
2006.12.13
Objectives
• HIV Lipodystrophy– Clinical Relevance– Clinical Manifestations– Pathophysiology– Treatment
Drug (abbreviations) Brand name Nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs) Abacavir (ABC) Ziagen® Didanosine (ddI) Videx®, Videx® EC Emtricitabine (FTC) Emtriva® Lamivudine (3TC) Epivir® Stavudine (d4T) Zerit® Tenofovir (TDF) Viread®* Zalcitabine (ddC) Hivid® Zidovudine (ZDV, AZT) Retrovir®
Non-nucleoside reverse transcriptase inhibitors (NNRTIs) Delavirdine (DLV) Rescriptor® Efavirenz (EFV) Sustiva® Nevirapine (NVP) Viramune®
Protease inhibitors (PIs) Amprenavir (APV) Agenerase® Atazanavir (ATV) Reyataz® Darunavir (DRV) Prezista® Fosamprenavir (FPV) Lexiva® Indinavir (IDV) Crixivan® Lopinavir/ritonavir (LPV/r) Kaletra Nelfinavir (NFV) Viracept® Ritonavir (RTV) Norvir®
Saquinavir (SQV) Fortovase®, Invirase®
Tipranavir (TPV) Aptivus®
Fusion inhibitor
Enfuvirtide (T-20) Fuzeon®
Prevalence of PI-related Dyslipidemia
• NOT an UNCOMMON issue – ~50%
• 47% of PI recipients at one clinic1
• 57% of PI recipients2
– LDL: 19%– TG: 44%– LDL + TG: 37%
*1Henry K, Lancet 1998, 2Behrens G, AIDS 1999
Case: Ms. TH
• 38F, HIV+ since ’86, HAART since ‘93
• Significant FHx of CAD, current smoker, +metabolic syndrome
• Lipodystrophy: new since HAART
• Dyslipidemia: new since HAART– TC 4.94, TG 5.11, HDL 0.80– Started on Ezetrol 10 mg daily
Questions
• What kinds of metabolic changes are associated with antiretroviral therapy in HIV?– Pathophysiology?
• What is Ms. TH’s risk of developing CVD?– Should her dyslipidemia be treated?
• To what targets?
Case: Mr. GM
• Mr. GM– 41M, HIV + since 1991– ++Opportunistic infections
• CMV retinitis, oral candidiasis
– Mega-HAART treatment: • d4T, DDI, Kaletra, Amprenavir, Sustiva• CD4 155 (improved), viral load 67 (improved)
Drug (abbreviations) Brand name Nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs) Abacavir (ABC) Ziagen® Didanosine (ddI) Videx®, Videx® EC Emtricitabine (FTC) Emtriva® Lamivudine (3TC) Epivir® Stavudine (d4T) Zerit® Tenofovir (TDF) Viread®* Zalcitabine (ddC) Hivid® Zidovudine (ZDV, AZT) Retrovir®
Non-nucleoside reverse transcriptase inhibitors (NNRTIs) Delavirdine (DLV) Rescriptor® Efavirenz (EFV) Sustiva® Nevirapine (NVP) Viramune®
Protease inhibitors (PIs) Amprenavir (APV) Agenerase® Atazanavir (ATV) Reyataz® Darunavir (DRV) Prezista® Fosamprenavir (FPV) Lexiva® Indinavir (IDV) Crixivan® Lopinavir/ritonavir (LPV/r) Kaletra Nelfinavir (NFV) Viracept® Ritonavir (RTV) Norvir®
Saquinavir (SQV) Fortovase®, Invirase®
Tipranavir (TPV) Aptivus®
Fusion inhibitor
Enfuvirtide (T-20) Fuzeon®
Mr. GM
0
5
10
15
20
25
30
35
1 2 3 4 5 6 7
TG
TC
HDL
JanMar
May June
July4 yrs
Ezetrol
Lipidil + Dietary
Questions
• Does Mr. GM’s lipid profile present a significant risk?– Long term outcomes?
• What are the best treatment options for his dyslipidemia?– Interactions with HAART
HIV Lipodystrophy
• Changes in fat distribution often associated with metabolic abnormalities– Insulin resistance– Hyperglycemia– Dyslipidemia– C peptide > 2.5 mmol/L– Lipoatrophy
• Loss of subcutaneous fat (Limbs, Face, Buttocks)
– Lipohypertrophy• Abdomen (Visceral Fat, Buffalo Hump, Breast enlargement)
+/- prominence leg/arm veins
Lipodystrophy Syndrome(s)
Fat atrophy
Fat accumulation
Lipidabnormalities
Dysregulation of glucose metabolism
HIV Dyslipidemia
• Dyslipidemia of Chronic Infection– Initially: HDL, LDL, and TC– More advanced disease: TG
• Dyslipidemia specific to antiretrovirals, specifically PI’s (Protease Inhibitors)– TG, TC, LDL
Pathophysiology
• Dyslipidemia secondary to HIV infection– Typical of dyslipidemia observed in chronic
infections– Interferon-α: natural course of HIV
• clearance, production TG• ?direct vs indirect effects on lipid metabolism
– TNF (acute phase reactant)• only during opportunistic infections• May exacerbate TC, HDL, LDL
Pathophysiology
• PI-associated HIV Dyslipidemia– Not fully understood– Multiple mechanisms likely involved
• Structural Similarities (CRABP-1 and LRP)• CYP 3A inhibition• Direct stimulation hepatic TG synthesis• Mitochrondrial alterations• Genetic Predisposition
CRABP-1
• Structural similarity– Catalytic region of HIV-1 protease– Cytoplasmic retinoic acid-binding protein type
1 (CRABP-1) – PI binds to CRABP-1 instead of viral protease
• Reduced RXR-PPARγ activity: increased apoptosis, diminished peripheral adipocyte proliferation
• Peripheral lipoatrophy, hyperlipidemia
LRP
• Structural similarity– Catalytic region of HIV-1 protease– Low-density lipoprotein-receptor-related
protein (LRP)– PI binds to LRP-LPL complex
• Inhibits FFA cleavage from TG: promotes FFA accumulation in peripheral adipocytes
– LDL and VLDL
Increased Hepatic TG Synthesis
• PIs may directly stimulate hepatic TG synthesis– Several PIs upregulate mRNA production for
key enzymes in TG biosynthetic pathway
Mitochondrial Alterations
• HAART (multiple NRTIs) inhibits mitochondrial DNA polymerase γ mitochondrial DNA depletion
mitochondrial respiratory chain dysfunction reduced cell energy production
– Abnormalities in adipocytes• Lipodystrophy syndrome• Hyperlipidemia
Genetic Predisposition
• Apo CIII gene– Association between TG (with HDL) and
several polymorphisms• Variations at -455 and -482 associated with
VLDL and HDL• Carriers of -455 variant 30% lower HDL levels• Plasma lipid concentrations increase according to
# variant alleles
Why It Matters
Psychosocial• Self-esteem
• Stigmatization• Mood disorders• Adherence with ART
Clinical• Pain
– Neck– Lower back– Breast
• Breathing problems• Umbilical hernia• GERD• Adherence with ART
Cardiovascular Complications
• Introduction of HAART has changed the natural history of HIV disease– Notable extension of life expectancy– Chronic and manageable disease– Prolonged metabolic alterations
• ?affect on long-term prognosis and outcome of HIV-infected persons
• Well known cardiovascular risk factors– Dyslipidemia, Insulin Resistance, Overt Diabetes Mellitus
Metabolic Changes
• CV disease takes time to develop
• The older one is, the more important CHD becomes
▲
CV Risk
Risk HIV disease
progression
Why It Matters: MI in HIV Study Event N Comment
HOPS*1 21 MI 5,672 Risk of MI PI vs no PI
German2 29 MI 4,993 Risk of MI prior HAART
Johns Hopkins3
43 CHD 2,671 Risk of CHD HIV+ vs HIV–
French4 49 MI 19,975 on PI
Risk of MI on PI vs HIV–
CA Medicaid5
N/A 28,513 Risk of CHD with ART in 18–33 yr olds, but not older individuals
Kaiser6 65 MI 4,408 Risk of MI HIV+ vs HIV–No greater risk on PIs
D:A:D*7 126 MI 23,468 Risk with HAART
VA8 1,207 CHD 36,766 risk of MI in HAART era
1. Holmberg 9th CROI, Seattle, 2002, #698; 2. Rickerts Eur J Med Res 2000;5:329; 3. Moore 10th CROI, Boston, 2003 #132; 4. Mary-Krause 8th CROI, Chicago, 2001, #657; 5. Currier 4th Int Workshop on Adverse Events and Lipodystrophy, San Diego, 2002; 6. Klein et al. 10th CROI, Boston, 2003 #747; 7. Friis-Møller ibid, #130; 8. Bozzette NEJM 2003
D:A:D Study, NEJM 2003
26% relative risk increase MI / yr over first 4~6 yrs
Friis-Møller, NEJM, 2003
Approach to Management
• Search for secondary contributory causes– Hypothyroidism– Chronic liver disease– Chronic renal failure– Diabetes Mellitus– Familial Hypercholesterolemia– Obesity– Alcohol Abuse
Approach to Management
• Search for secondary contributory causes– Medications
• Beta Blockers• Diuretics• Steroid Derivatives• Oral Contraceptives• Hormonal Treatment
Treatment of Dyslipidemia
• Lifestyle Interventions
• Switching Antiretrovirals
• HMG CoA-Reductase Inhibitors
• Fibrates
• Niacin
• Alternative Treatments
Guidelines
• “For the purposes of initiating therapy for dyslipidemia, the Panel recommends that the NCEP guidelines should generally be followed for HIV-infected patients. Of note, the new NCEP guidelines now include a category termed CHD “risk equivalents,” which include diabetes mellitus, other atherosclerotic disease, and multiple risk factors that confer a 10-year risk of CHD of >20%. Because of the high risk of CHD in these groups, these individuals should be treated as aggressively as those with established CHD.”*
*Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the NCEP Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001; 285:2486-97.
Guidelines
• “When TG levels exceed 200 mg/dL, calculation of non-HDL-C should be performed and considered a secondary target for intervention.”
• “In addition, the high frequency of low HDL-c in persons with HIV warrants attention.”
*Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the NCEP Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001; 285:2486-97.
Lifestyle Interventions
• Diet & Exercise– Thorough trial of non-drug therapies
• Efficacy may be limited– TC by 11%, TG by 21% (Henry K, Lancet, 1998)
– Competing dietary needs frequently identified• Need to lean muscle mass but lipid level
– Dietary options often limited• Prominent GI symptoms in advanced HIV
Dietary Intervention
• Recent Brazilian abstract– Randomized trial: 47 patients new to HAART
• Control: general guidelines on dietary education• Intervention: above + nutritional follow-up every 3
months based on NCEP-ATPIII
– Direct Dietary Orientation prevented the development of dyslipidemia at 6 months
• Extended to 1 year*R. Lazzaretti, 2006, AIDS Conference, Toronto
Lifestyle Interventions
• Treat/Control Other Modifiable Cardiovascular RF’s– Smoking– Glycemic Control in DM– Hypertension
PI-Related Dyslipidemia
• VLDL >> IDL, HDL no change
• TG
• Ritonavir > Amprenavir/Nelfinavir> Indinavir/Saquinavir > Atanavir
• Atanavir associated with minimal/no significant dyslipidemia
• (Mobius, J Acquir Immune Defic Syndr 2005 & Cahn, J Int Assoc Physicians AIDS Care, 2004)
Drug (abbreviations) Brand name Nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs) Abacavir (ABC) Ziagen® Didanosine (ddI) Videx®, Videx® EC Emtricitabine (FTC) Emtriva® Lamivudine (3TC) Epivir® Stavudine (d4T) Zerit® Tenofovir (TDF) Viread®* Zalcitabine (ddC) Hivid® Zidovudine (ZDV, AZT) Retrovir®
Non-nucleoside reverse transcriptase inhibitors (NNRTIs) Delavirdine (DLV) Rescriptor® Efavirenz (EFV) Sustiva® Nevirapine (NVP) Viramune®
Protease inhibitors (PIs) Amprenavir (APV) Agenerase® Atazanavir (ATV) Reyataz® Darunavir (DRV) Prezista® Fosamprenavir (FPV) Lexiva® Indinavir (IDV) Crixivan® Lopinavir/ritonavir (LPV/r) Kaletra Nelfinavir (NFV) Viracept® Ritonavir (RTV) Norvir®
Saquinavir (SQV) Fortovase®, Invirase®
Tipranavir (TPV) Aptivus®
Fusion inhibitor
Enfuvirtide (T-20) Fuzeon®
Switching Antiretrovirals
• Ensure no compromise in control of HIV infection when switching medications
Switching Antiretrovirals
• Switching to a less dyslipidemic PI– Atazanavir
• Not associated with significant TG, TC, LDL• Simplifies treatment (once daily dosing)• No impact on viral load, CD4 count• Nelfinavir Atazanavir
•(Mobius, J Acquir Immune Defic Syndr 2005 & Cahn, J Int Assoc Physicians AIDS Care, 2004)
NNRTI-Related Dyslipidemia
• Associated with dyslipidemia– TC, LDL– BUT HDL, TG– Lesser degree than PIs
Switching Antiretrovirals
• Switching PI for Abacavir1
– Improved lipid profile– No change CD4 counts, viral load
• Stavudine Tenofovir2
– Sustained improvement of dyslipidemia– Significant reduction of cardiovascular risk– Differences amongst various NNRTIs
• dyslipidemia
1. Keiser, BMC Infect Dis 2005. 2. Llibre, AIDS 2006.
Drug (abbreviations) Brand name Nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs) Abacavir (ABC) Ziagen® Didanosine (ddI) Videx®, Videx® EC Emtricitabine (FTC) Emtriva® Lamivudine (3TC) Epivir® Stavudine (d4T) Zerit® Tenofovir (TDF) Viread®* Zalcitabine (ddC) Hivid® Zidovudine (ZDV, AZT) Retrovir®
Non-nucleoside reverse transcriptase inhibitors (NNRTIs) Delavirdine (DLV) Rescriptor® Efavirenz (EFV) Sustiva® Nevirapine (NVP) Viramune®
Protease inhibitors (PIs) Amprenavir (APV) Agenerase® Atazanavir (ATV) Reyataz® Darunavir (DRV) Prezista® Fosamprenavir (FPV) Lexiva® Indinavir (IDV) Crixivan® Lopinavir/ritonavir (LPV/r) Kaletra Nelfinavir (NFV) Viracept® Ritonavir (RTV) Norvir®
Saquinavir (SQV) Fortovase®, Invirase®
Tipranavir (TPV) Aptivus®
Fusion inhibitor
Enfuvirtide (T-20) Fuzeon®
Statins
• First line therapy for hypercholesterolemia in general population
• Considerable evidence to demonstrate benefits in reducing CHD risk– 1° and 2° prevention
Statins
• Generally, studies show modest efficacy with good tolerability
• Potential for interaction with HAART medications level statin– CYP 3A4-metabolized medications:
• PIs and NNRTIs• Most statins• Cyclosporine, erythromycin, itraconazole, oral
anticoagulants
Statins in HIV Dyslipidemia Agent Considerations
Lovastatin (Mevacor®)
Simvastatin (Zocor®)
Extensively metabolized by CYP3A4; toxicity likely when combined with PIs.
Fluvastatin (Lescol®) Metabolized by CYP2C9; interaction with nelfinavir likely.
Cerivastatin (Baycol®)
Off market
Atorvastatin (Lipitor®)
Some CYP3A4 metabolism; small amount of anecdotal and research experience in HIV. Modest increases in AUC when coadministered with ritonavir-saquinavir.
Pravastatin (Pravachol®)
No significant p450 interactions; primarily renal excretion. Minimally decreased AUC when coadministered with ritonavir-saquinavir.
Dube. Clin Infect Dis. 2000; 31:1216-24.
Relative Safety with 3A4 Inhibitors
Simvastatin Lovastatin
Fluvastatin
Pravastatin
Rosuvastatin
Atorvastatin
Statin and HAART Interactions
• Fluvastatin metabolized by CYP 2C9
• Pravastatin not significantly metabolized by CYP enzyme system– Lower risk of interactions with HAART– Reasonable to recommend low dose as 1st
line treatment for HAART-related dyslipidemia• Pravastatin 10 mg daily • Fluvastatin 20 mg daily
Statins: Recent Studies
no effects TC, TG-homocysteine,
Study Event N= Comment
Pravastatin 40 mg 1 1º: TWAUC2 º: total & regional body fat, fasting lipids, glucose, insulin, markers CV risk @ 16 wks
33 +subcutaneous fat-homocysteineNo significant effects TC, TG
Statins, Fibrates, Dual Therapy2
Lipid parameters @ 70 wks
103 TC: -7S/14F/22D%TG: -21S/40F/42D%
Statins, Fibrates3 Fasting lipids at 1 yr 106 Statin: -34.8% (TG) -25.2% (TC)Fibrate: -40.7% (TG), -21.9% (TC)
Rosuvastatin4 TG/TC @ 24 wks 16 TG -30.1%, TC 21.7%
Combination Fenofibrate and Pravastatin5
LDL/HDL/TG/non-HDLc @ 48 wks
174 Substantial improvements, but unlikely to meet guidelines
Fibrates vs Statin6 TG/TC @ 3 and 12 months
245 TG: significant improvementsTC: only significant at 3 months
1.Mallon, AIDS 2006. 2. Aberg, AIDS Res Hum Retrovir 2005. 3.Visnergarwala, J Infect 2004. 4. Calaz, AIDS 2005. 5.Benesic, Infection 2004. 6. Bonnet, HIV Med 2004.
TC
0
2
4
6
8
10
12
baseline 10mg
mm
ol\
L
8.04+2.15 6.67+1.5617.1% decrease
Ezetimibe in Antiretroviral Dyslipdemia
*R Hegele, unpublished data
Ezetimibe in Antiretroviral Dyslipdemia
TG
0
2
4
6
8
10
12
baseline 10mg
mm
ol\
L
5.90+3.41 4.39+3.16
25.6% decrease
*R Hegele, unpublished data
Ezetimibe in Antiretroviral Dyslipdemia
HDL
0
0.5
1
1.5
2
2.5
baseline 10mg
mm
ol\
L
1.17+0.54 1.27+0.53
8.7% increase
*R Hegele, unpublished data
Ezetimibe in Antiretroviral Dyslipdemia
LDL
0
1
2
3
4
5
6
7
8
baseline 10mg
mm
ol\
L
3.47+3.03 2.98+0.9713.94% decrease
*R Hegele, unpublished data
Fibrates
• Well established tolerability and efficacy profile in mixed hyperlipidemia and TG
• Favorable but moderate effect on serum lipids, well tolerated
• Similar efficacy as statins in dyslipidemia
• Concomitant use of statins and fibrates cautioned– Risk of skeletal muscle toxicity
Fibrates
• Comparisons between fibrates– Gemfibrozil
• Safe, but moderate efficacy (questionable clinical significance)1
– Fenofibrate• Improves clinical atherogenic profile
– -40% TG, -14% TC, -21% apoCIII, -17% apoB, -17% non-HDLc
– +15% HDL, +11% apoA1
1. Miller, AIDS 2002. 2. Badiou, Atherosclerosis 2004.
Niacin
• Effective therapy for hypertriglyceridemia• Use has been cautioned in PI-related
dyslipidemia– Flushing, cutaneous rash, pruritis, insulin resistance
• One study with extended release Niacin1
– Significant decreases in TC (14%), TG (34%), non-HDL c (19%)
– No significant decrease in LDL or HDL– Insulin resistance was an issue– Well tolerated with good safety profile
• Most side effects gone with ASA 325 mg daily
1. Gerber, Clin Infect Dis 2004.
Niacin• Acipimox
– Nicotinic acid analogue, potent inhibitor of lipolysis
– Recent study evaluating apicimox use in HIV patients with TG
• Contributory factors to dyslipidemia: Insulin resistance, ++lipolysis, ++ FFAs
• FFAs (-68%), -lipolysis, improved insulin sensitivity, modest but significant –TGs
• Potential clinical utility of apicimox in HIV dyslipidemia
*Hadigan C, JCEM 2006
Fish Oil
• Mixed results with various studies• TGs (19.5%)• Associated LDL (22%) over 16 wks• Contribution of fish oil to LDL unclear• Whether this negates benefits of TG unclear• PEE (polyunsaturated ethyl esters) vs fibrates
– Fibrates>PEE TG
• Further investigation warranted
*Woods, Nutr Clin Care 2005, Wohl, CID 2005.
TTA
• Tetradecylthioacetyl acid– Potential lipid lowering and immuno-
modulatory properties
• Small study (n=10)– TTA + dietary intervention may be therapeutic
approach– Larger efficacy of dietary intervention than
previously reported studies– -TNFα levels
*Fredrikson, Eur J Clin Invest 2004.
Leptin
• 1 randomized, double-blinded, placebo controlled study (n=7)– Effect of r-metHu leptin on metabolic
abnormalities evaluated• Improves insulin resistance, fasting insulin levels,
HDL, truncal fat mass
• Future studies warranted to further explore mechanisms and therapeutic role
*Lee J, JCEM 2006.
Switching Antiretrovirals
• Use of thymidine analogue NRTIs strongly associated with lipoatrophy
• Stavudine>zidovudine• Epidemiological studies & clinical trials• Stavudine/Zidovudinealternative nucleoside analog agents
– Modest gains in limb fat
– Use of PIs + NRTIs may accelerate lipoatrophy• Observational data• PINNRTI or Abacavir
– 36% increase limb fat at 2 years
• (Mallal, AIDS 2000)
Prevention
• Randomized, double blind comparison in antiretroviral naïve patients– Stavudine vs tenofovir (+efavirenz & lamivudine)
• Tenofovir group: normal limb fat @ 133 weeks• Stavudine group: significant decline lower limb fat mass in
nearly 50% of patients• No baseline assessments done
• Open label– Tenofovir/emtricitabine vs Zidovudine/lamivudine
+Efavirenz• Primary endpoint virologic efficacy (@ 48 weeks)• Subset analysis: total limb fat less by DEXA in Zidovudine
group
*Carr, Jama 2002. Martin, AIDS 2004.
Thiazolidinediones
• Visceral Fat, Insulin Sensitivity in congenital forms of (non-HIV) lipodystrophy – Rosiglitazone for HIV-associated lipoatrophy
• Data conflicting, remains investigational• Improvements in insulin sensitivity, but TC, TG• Possible limb fat
*Sustinen, Ann Intern Med 2004.
Uridine
• Pyrimidine nucleoside
• Protects adipocytes from adverse effects of thymidine analogues
• NucleomaxX® increases uridine levels– Sugar cane derived dietary supplement– Preliminary results of small, randomized trial
suggests favorable effects on limb fat• Larger, randomized trial underway
*Sustinen, Abstract, 2005.
Leptin
• Pilot study– Improvement in fasting insulin levels, insulin
resistance, and HDL levels, truncal fat mass
*Lee J, JCEM 2006.
Surgical Approaches
• Various injectable fillers to fill in space vacated by facial lipoatrophy– Permanent: purified silicone oil,
polymethylmethacrylate, polyalkylamide, polytetrafluoroethylene (non-FDA approved)
– Temporary: poly-L-lactic acid (PLLA/SculptraTM)- used in dissolvable sutures/dental implants, non-FDA approved: bovine/human collagen, hyaluronic acid, autologous fat
• 50 patients: mean dermal thickness by U/S– 7 mm at 96 weeks
*Sustinen, Curr Opin Infect Dis 2005.
Before 15 months7 months
‘Hamster Syndrome’: hypertrophy of fat transferred to face
“Hamster Syndrome”
*Google Images
Exercise
• Safe & potentially useful in patients with abdominal fat accumulation
• Limited efficacy data
• Individualized, supervised, aerobic training program– Preferential loss of visceral fat and
improvements in TC, TG and HDL at 4/12
*Thoni, Diabetes Metab 2002.
Metformin
• Randomized Placebo Controlled Trial– Metformin 500 mg bid x 3 months in HIV
patients with central obesity and hyperinsulinemia
• Improved insulin sensitivity, reduced visceral and subcutaneous abdominal fat, improved markers of fibrinolysis
• Cannot be recommended to reduce truncal fat in non-diabetic patients
– Risk/benefit ratio not well defined
• Avoid in patients who predominantly have moderate to severe lipoatrophy
*Hadigan, JAMA 2000
Growth Hormone and Related Drugs
• Phase II trials rhGH (recombinant human GH/Serostim®)
• visceral and subcutaneous abdominal fat
• LDL, HDL
• Side effects– Fluid retention, arthralgias, myalgias, carpal
tunnel syndrome, diabetes mellitus
*Schambelan, Ann Intern Med 1996
*Engelson, J Acquir Immune Defic Syndr 2002.
Surgical Approaches
• Suction assisted lipectomy (liposuction) for dorsocervical fat accumulation– Recurrent fat accumulation
• Reduction mammoplasty for breast enlargement
Switching Antiretrovirals
• Clear associations between fat accumulation and specific antiretroviral agents less apparent
Conclusions
• HIV lipodystrophy is an important clinical problem– QOL Issues affecting treatment compliance– Increased risk of medical complications
• Dyslipidemia in HIV should be treated aggressively– Antiretroviral efficacy, resistance, side effects
• Future studies and analyses will help further define optimal treatment of HIV dyslipidemia
Recommended