Behcations

Metabolic Complications of HIV Infection and HAART

Christopher Behrens, MD

University of Washington

Metabolic Complications of HIV Infection and HAART

• Lactic Acidemia

• Lipodystrophy

• Dyslipidemia

• Insulin Resistance

• Cardiovascular Disease

• Bone Mineralization Disorders

Lactic Acidemia & Lactic AcidosisDefinitions

• Lactic Acidemia: serum lactate level greater than 2.0 mmol/L in conjunction with a normal serum pH– Common in HIV-infected patients on HAART– Varying degrees of severity– Often asymptomatic

• Lactic Acidosis: serum lactate level greater than 2.0 mmol/L in conjunction with a serum pH less than 7.30– Reflects most serious form of lactic acidemia– Rare but potentially fatal– Common signs & symptoms include lethargy, fatigue, weight loss,

nausea, abdominal pain, and dyspnea– Concomitant hepatotoxicity common with hepatomegaly, hepatic

steatosis, and even ascites and encephalopathy

Schambelan M et al. JAIDS 2002;31:257-75

CELL

glucose

pyruvatelactate

Acetyl CoA Krebscycle

NADHFADH2

OxidativephosphorylationATP

NRTI-induced mitochondrial toxicity

Proposed Pathogenesis

MITOCHONDRION

Fatty Acids

CELL

glucose

pyruvatelactate

Acetyl CoA Krebscycle

NADHFADH2

OxidativephosphorylationATP

NRTI-induced mitochondrial toxicity Proposed Pathogenesis

MITOCHONDRION

mtDNADNA pol γ

Fatty Acids

CELL

glucose

pyruvatelactate

Acetyl CoA Krebscycle

NADHFADH2

OxidativephosphorylationATP

MITOCHONDRION

mtDNADNA pol γ

Fatty Acids

NRTIs

NRTI-induced mitochondrial toxicity Proposed Pathogenesis

CELL

glucose

pyruvatelactate

Acetyl CoA Krebscycle

NADHFADH2

OxidativephosphorylationATP

NRTI-induced mitochondrial toxicity

Proposed Pathogenesis

MITOCHONDRION

mtDNADNA pol γ

Fatty Acids

NRTIs

CELL

glucose

pyruvatelactate

Acetyl CoA Krebscycle

NADHFADH2

OxidativephosphorylationATP

NRTI-induced mitochondrial toxicity

Proposed Pathogenesis

MITOCHONDRION

mtDNADNA pol γ

Fatty Acids

NRTIs

CELL

glucose

pyruvatelactate

Acetyl CoA Krebscycle

NADHFADH2

OxidativephosphorylationATP

NRTI-induced mitochondrial toxicity Proposed Pathogenesis

MITOCHONDRION

mtDNADNA pol γ

Fatty Acids

NRTIs

CELL

glucose

pyruvatelactate

Acetyl CoA Krebscycle

NADHFADH2

OxidativephosphorylationATP

NRTI-induced mitochondrial toxicity

Proposed Pathogenesis

MITOCHONDRION

mtDNADNA pol γ

Fatty Acids

NRTIs

CELL

glucose

pyruvatelactate

Acetyl CoA Krebscycle

NADHFADH2

OxidativephosphorylationATP

NRTI-induced mitochondrial toxicity

Proposed Pathogenesis

MITOCHONDRION

mtDNADNA pol γ

Fatty Acids

NRTIs

Classification of Lactic Acidemia

*Symptoms and signs that suggest lactic acidemia consist of nausea, vomiting, abdominal pain, weight loss, fatigue, myalgias, abdominal distention, abdominal pain, dyspnea, and cardiac dysrhythmias.

Source: HIV Web Study (www.hivwebstudy.org); Schambelan M et al. JAIDS 2002;31:257-75

NRTIs have different levels of mitochondrial toxicity

• rank: ddC / ddI / d4T > 3TC > ZDV > ABC for effects on mitochondrial DNA

polymerase gamma1

• tenofovir has low affinity for mitochondrial polymerase gamma as well2

• However, cases of severe hyperlactatemia have been reported in association with all NRTIs3

1. Kakuda TN. Clin Ther 2000 Jun;22(6):685-7082. Johnson AA et al. J Biol Chem 2001 Nov 2;276(44):40847-57 3. Schambelan M et al. JAIDS 2002;31:257-75

Risk Factors for the Development of Lactic Acidemia in Persons Taking NRTIs

*Most cases have involved stavudine**Especially with the use of stavudine plus didanosine

Source: HIV Web Study (www.hivwebstudy.org)

Hyperlactatemia & Lactic AcidosisMeasuring Serum Lactate Levels

no vigorous exercise for 24 hours prior

Draw without tourniquet and fist clenching

Use pre-chilled gray top (fluoride-oxalate) tube

Place on ice and promptly send to lab/process within 4

hours

If increased, confirm with repeat measurement

Arterial pH measurement if frank acidosis suspected

Schambelan M et al. JAIDS 2002;31:257-75.

Recommendations for the Management of Lactic Acidemia

Source: HIV Web Study (www.hivwebstudy.org); Carr A. Clin Infect Dis 2003;36 (Suppl 2):S96-100.

Case• 44 year old male with C3 AIDS, well-controlled on HAART

regimen of d4T/3TC/Efavirenz• Develops severe lactic acidosis and is admitted to the ICU• Recovers with discontinuation of HAART and supportive

care, but CD4 count now 290, HIV viral load 66,000 copies/mL

• What are your recommendations regarding antiretroviral therapy?

1. Do not resume HAART – continue to monitor2. Resume HAART with Kaletra + Efavirenz3. Resume HAART with TDF + 3TC + Efavirenz4. Resume prior HAART regimen, supplemented with L-

carnitine5. I don’t know; just tell me the answer and get on with the

talk

Resumption of Antiretroviral Therapy after Lactic Acidosis

• NRTI-sparing regimen? – Promising early results from trials of efavirenz +

ritonavir/lopinavir1

• Addition of mitochondrial-supporting compounds as prophylaxis against recurrent lactic acidosis?– Limited evidence of benefit in hastening recovery of

patients with lactic acidosis, but efficacy in preventing the condition has not been established2-4

• re-initiation of therapy using ‘mitochondria-sparing’ NRTIs (tenofovir, abacavir, 3TC, AZT)? – reasonably safe in two studies5,6

1. Allavena C et al. JAIDS 2005;39(3):300-306. 2. Fouty B et al. Lancet. 1998;352:291-2. 3. Lenzo NP et al. AIDS. 1997;11:1294-6.

4. Schramm C et al. Eur J Anaesthesiol. 1999;16:733-5. 5. Lonergan JT et al. AIDS. 2003;17:2495-9.6. ESS40010 Study Team. JAIDS. 2004;36:935-42.

Case• 44 year old male with C3 AIDS, well-controlled on HAART

regimen of d4T/3TC/Efavirenz• Develops severe lactic acidosis and is admitted to the ICU• Recovers with discontinuation of HAART and supportive

care, but CD4 count now 290, HIV viral load 66,000 copies/mL

• What are your recommendations regarding antiretroviral therapy?

1. Do not resume HAART – continue to monitor2. Resume HAART with Kaletra + Efavirenz3. Resume HAART with TDF + 3TC + Efavirenz4. Resume prior HAART regimen, supplemented with L-

carnitine5. I don’t know; just tell me the answer and get on with the

talk

Lipodystrophy

Case 1

• 41 year old HIV+ man on PI-based HAART presents for routine followup

• Complains of recent weight gain, especially in the abdomen

• “It’s the protease paunch!”

Case 1

• 41 year old HIV+ man on PI-based HAART presents for routine followup

• Complains of recent weight gain, especially in the abdomen

• “It’s the protease paunch!”

HIPAA

Case 1 continued

• PMH: – HIV-infected x 5 years

• well-controlled on HAART

• Nadir CD4 140, most recent 360

• No OIs, though radiology studies have suggested HIV encephalopathy

– Hypertension

• Medications– d4T + 3TC + Kaletra

(ritonavir/lopinavir) x 2 years

– Enalapril 10mg qd

Case 1 continued

• PE: obese abdomen, otherwise unremarkable

What intervention would you recommend?

A. Ask his wife to padlock the fridge and get him a treadmill

B. Discontinue lopinavir/ritonavir, substitute an NNRTI such as efavirenz or nevirapine

C. Start metformin 500mg bidD. LiposuctionE. None of the above have been demonstrated

to improve HIV-associated visceral fat accumulation

HIV/HAART Toxicities: Lipodystrophy

• Constellation of body habitus changes– Fat accumulation (lipohypertrophy): central (esp.visceral)

fat, dorso-cervical fat pads (buffalo humps), breasts, lipomata, within muscle & liver

– Fat wasting (lipoatrophy): face, extremities, buttocks, and trunk

• Lack of clear case definition has hampered clinical research: wide variation in reported prevalence

• Increasing evidence that lipoatrophy and lipohypertrophy are distinct entities, though can occur simultaneously

• Hyperlipidemia and insulin resistance also variably present

facial lipoatrophy

central adiposity

peripheral lipoatrophy

breast enlargement

Lipoatrophy

N Engl J Med 2005;352:48-62.

Dorsocervical Fat Pad

FRAM: Defining Lipodystrophy• N = 565 men 33-45 years old

– 412 HIV+ w/o OI’s in past month– 153 HIV-negative controls from

CARDIA study

• examined fat loss/deposition in peripheral sites (cheeks, face, arms, legs, buttocks) and central sites (waist, abdomen, neck, chest, upper back)

• Peripheral and central lipoatrophy more common in HIV+ subjects

• Central lipohypertrophy more common in HIV-negative subjects

• Lack of concordance between lipoatrophy and lipohypertrophy

0

10

20

30

40

50

60

peripherallipoatrophy

centrallipoatrophy

central fatdeposition

HV positive

HIV negative

p < 0.05 for all

Results for concordant self-report & exam

% o

f pa

tien

ts

Gripshover B et al. 10th CROI, Boston, 2003, Abstract 732.

Risk Factors for Lipoatrophy and Lipohypertrophy

Lichtenstein KA. JAIDS 2005;39:395-400.

Percentage of studies showing statistically significant associations between risk factors and either lipoatrophy (LA) (9 studies) or lipohypertrophy (LH) (8 studies) using multivariate analysis.

Lipohypertrophy

Risk Factors

Pathophysiology

Interventions

Lipohypertrophy: Risk Factors

• Duration of antiretroviral therapy

• Use of Protease Inhibitors

• Markers of disease severity

• Age • Female gender

Lichtenstein KA. JAIDS 2005;39:395-400.

Percentage of studies showing statistically significant associations between risk factors and lipohypertrophy (LH) (8 studies) using multivariate analysis.

Lipohypertrophy: Pathophysiology

• dysregulation of 11-beta-hydroxysteroid dehydrogenase?

• Dysregulation of adipocyte differentiation and/or function?

• ????

Lipohypertrophy: Treatment Options

• diet/exercise1-4

1. Jones SP et al. AIDS 2001 Oct 19;15(15):2049-51 2. Roubenoff R et al. Clin Infect Dis 2002 Feb 1;34(3):390-33. Roubenoff R et al. AIDS. 1999;13:1373-1375.4. Thoni GJ et al. Diabetes Metab. 2002;28:397-404.

Lipohypertrophy: Treatment Options

• diet/exercise

• Switching Protease Inhibitors out of HAART regimen: inconsistent results

Drechsler H, Powderly WG. Clin Infect Dis. 2002;35:1219-1230.

Lipohypertrophy: Treatment Options

• diet/exercise

• Switching Protease Inhibitors out of HAART regimen: inconsistent results

• Diabetes Agents?– Patients with lipodystrophy often

demonstrate insulin resistance as well

• N = 26 patients on antiretroviral therapy with insulin resistance and fat redistribution

• randomized to metformin or placebo for 12 weeks

1191

-1115-1500

-1000

-500

0

500

1000

1500

Placebo

Metformin

Hadigan C et al. JAMA 2000;284:472-7.

p = 0.08

Metformin Therapy for Lipohypertrophy?

Mea

n ch

ange

in v

isce

ral a

bdom

inal

fat

, mm

3

Lipohypertrophy: Treatment Options

• diet/exercise

• Switching Protease Inhibitors out of HAART regimen: inconsistent results

• Diabetes Agents?

• Plastic Surgery?

Surgical Correction ofBuffalo Hump?

• Liposuction or surgical excision a reasonable option, esp. if pain or functional limitations

• Only small studies to date• Generally well-tolerated

with favorable initial results • Conflicting data regarding

recurrence: One study found a recurrence rate of just 5% (1/18 patients)1 while another study reported a recurrence rate of 50% (5/10 patients)2

1. Gervasoni C et al. 10th CROI, Boston, 2003. Abstract 723.2. Piliero PJ et al. 10th CROI, Boston, 2003. Abstract 724.

What intervention would you recommend?

A. Ask his wife to padlock the fridge and get him a treadmill

B. Discontinue lopinavir/ritonavir, substitute an NNRTI such as efavirenz or nevirapine

C. Start metformin 500mg bidD. LiposuctionE. None of the above have been demonstrated

to improve HIV-associated visceral fat accumulation

Case 2

• 43 year old woman with history of PCP now doing well on HAART: d4T/3TC/ritonavir/lopinavir

• She complains that her cheeks appear sunken and the veins in her arms and legs are more prominent

What intervention would you recommend for her condition?

A. Discontinue Kaletra, substitute atazanavir or an NNRTI

B. Discontinue d4T, substitute abacavir or tenofovir

C. Initiate rosiglitazone therapy

D. Plastic surgery: facial injections

E. None of these interventions are likely to help

Lipoatrophy

Risk Factors

Pathophysiology

Interventions

Lipoatrophy: Risk Factors• Antiretroviral Therapy

– HAART, esp. 2 NRTIs plus PI– d4T, esp. when used with ddI– Hierarchy: d4T/ddI/ddC > AZT > TDF/ABC/3TC

• Older age• Lower body weight before therapy• Prior AIDS diagnosis• Lower CD4 nadir• Caucasian race• Male gender?

Grinspoon S et al. N Engl J Med 2005;352:48-62.Podzamczer D et al. 11th CROI, 2004, Abstract 716.

Lichtenstein KA et al. JAIDS 2003;32:48-56.Joly V et al. AIDS 2002;16:2447-2454.

Dube M et al. 4th Int’l Workshop on Adverse Drug Reactions and Lipodystrophy in HIV, 2002, abstract 27.Shlay J et al. XV International AIDS Conference, 2004, Abstract ThOrB1360.

J Acquir Immune Defic Syndr 2002 February 1;29(2):117-121

? Etiology of Lipoatrophy: Evidence of Mitochondrial Toxicity in Adipocytes

HIV infection may independently contribute to mitochondrial toxicity

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

1.8

Non-HIV Infected(n = 24)

HIV Infected, naïveto antiretrovirals

(n = 47)

HIV Infected, withmitochondrial toxicity,before stopping ARVs

(n = 8)

HIV Infected, withmitochondrial toxicity,after stopping ARVs

(n = 7)

N Engl J Med 2002; 346:811-820, Mar 14, 2002.

mtD

NA

:nD

NA

rat

io

Lipoatrophy: Treatment Options

• Switching d4T out of regimen: evidence for slow reversal of lipoatrophy

Abacavir substitution for patients with subcutaneous lipoatrophy (LA)

• 111 patients with subjective LA on stable AZT- or d4T- containing HAART randomized to substitute abacavir or continue current regimen1

• limb fat mass measured by DEXA and by subjective physician assessment

• statistically significant increase in limb fat mass by DEXA at 104 weeks of follow-up2

• Similar findings from other studies3,4,5

1. JAMA 2002;288(2): 207-15.2. AIDS 2004;18:1029-36.3. CID 2004;38:263-270.

4. JAIDS 2003;33:22-8.5. JAIDS 2003;33:29-33.

Mean change in limb fat mass (intention-to-treat analysis)

Lipoatrophy: Treatment Options

• Switching d4T out of regimen: evidence for slow reversal of lipoatrophy

• Diabetes Agents?

- Rosiglitazone increases subcutaneous fat in type 2 diabetic patients and reverses the block of adipocyte differentiation induced by HAART in vitro

Rosiglitazone for Lipoatrophy?Discouraging results to date

• N=108 HIV-1-infected adults with LA on ART randomized to rosiglitazone 4 mg twice daily (n=53) or matching placebo (n=55) for 48 weeks1

• Limb fat increased by 0.14 kg in the rosiglitazone group and 0.18 kg in the placebo group (p=NS)

• Two other similar studies:– One showed no

improvement2

– One showed modest benefit3

1. Carr A et al. Lancet. 2004;363:429-438. 2. Sutinen J et al. Antivir Ther 2003;8:199-207. 3. Hadigan C et al. Ann Intern Med 2004;140:786-794.

Change in limb fat by DEXAwww.clinicaloptions.com

Lipoatrophy: Treatment Options

• Switching d4T out of regimen: evidence for slow reversal of lipoatrophy

• Diabetes Agents?

• Facial Injections?– Intradermal Injections of

Polylactic Acid

Valantin MA et al. AIDS 2003, 17:2471–2477

VEGA: 96 week results

Valantin MA et al. AIDS 2003, 17:2471–2477

What intervention would you recommend for her condition?

A. Discontinue Kaletra, substitute atazanavir or an NNRTI

B. Discontinue d4T, substitute abacavir or tenofovir

C. Rosiglitazone

D. Plastic surgery: facial injections

E. None of these interventions are likely to help

Dyslipidemia

Dyslipidemia: Case 1 continued

• He returns for followup 3 months later and reports some improvement with increased physical activity

• You check a fasting lipid panel

Case 1 continued

• Fasting lipid panel• Total cholesterol 320• Triglycerides 870• HDL cholesterol 32• LDL cholesterol: could not be calculated

What intervention(s) would you recommend to improve his lipids?

A. Discontinue lopinavir/ritonavir, substitute atazanavir

B. Discontinue d4T, substitute tenofovir

C. Ask his employer to replace the donuts with granola in the vending machine

D. Start simvastatin

E. Start gemfibrozil

F. Nothing needs to be done; dyslipidemia associated with HIV/HAART is not associated with an increase in CAD

• Decreased levels of HDL & LDL (especially HDL) and elevated triglycerides seen in HIV-infected patients prior to introduction of HAART

• Most protease inhibitors have been associated with marked elevations in triglycerides and LDL but little effect on HDL levels

• NNRTIs and stavudine also associated with dyslipidemic effects

• HIV infection and PI-based HAART each associated with pro-atherogenic profile dyslipidemia

• Substantial evidence that PI-based HAART increases risk of coronary artery disease2-4

HIV/HAART Toxicities: Dyslipidemias

1. Schambelan M et al. JAIDS 2002; 31(3):257-75.2. 11th CROI, 2004, Abstract 739.

3. 11th CROI, 2004, Abstract 736.4. 11th CROI, 2004, Abstract 737.

The DAD Study Group, N Engl J Med 2003;349:1993-2003

Incidence of Myocardial Infarction According to the Duration of Exposure to Combination Antiretroviral Therapy

The Data Collection on Adverse Events of Anti-HIV Drugs (DAD) Study Group, N Engl J Med 2003;349:1993-2003

• often improves with removal of offending agents from regimen

• treatment w/ fibrates and/or statins often indicated

• beware of drug interactions, risk of myositis

HAART- associated Dyslipidemias: Treatment

Switch HAART regimen or initiate lipid-lowering pharmacotherapy?

Trend of mean plasma triglyceride levels of 130 evaluable patients switched from protease inhibitor to nevirapine (arm A) or efavirenz (B), or treated with pravastatin (C) or bezafibrate (D), at baseline and after 3, 6, 9 and 12 months of follow-up. Calza L et al. AIDS 2005: 19(10), 1051-8.

Switch HAART regimen or initiate lipid-lowering pharmacotherapy?

Trend of mean plasma total cholesterol levels of 130 evaluable patients switched from protease inhibitor to nevirapine (arm A) or efavirenz (B), or treated with pravastatin (C) or bezafibrate (D), at baseline and after 3, 6, 9, and 12 months of follow-up.

Calza L et al. AIDS 2005: 19(10), 1051-8.

Lipid Lowering Agents and ARV Therapy:Potentially Dangerous Drug Interactions

Agent

Pravastatin

Atorvastatin

Lovastatin

Simvastatin

Gemfibrozil

Fenofibrate

Niacin

Bile sequestrants

No dose adjustment

Dose titration

Avoid

Avoid

No dose adjustment

No dose adjustment

Associated with insulin resistance

Avoid

Recommendation

Dube MP et al. Clin Infect Dis 2000;31:1216-24.

Treatment of HIV-Associated Hyperlipidemia: ACTG 5087

• N=174 HIV+ patients with dyslipidemia randomized to pravastatin 40mg qd (n=86) or fenofibrate 200mg qd (n=88)

• Fewer than 5% of patients responded to either drug alone in reaching target NCEP guidelines after 12 weeks

• 136 subsequently progressed to dual therapy with both agents

• Only 10% of patients responded to dual therapy after 12 more weeks

• Few adverse events with either mono- or dual therapy

36

9

49

66

18

48

5 110

010203040

5060708090

100

LDL Goal HDL goal TG goal Compositegoal

Compositegoal

pravastatin

fenofibrate

combinedtherapy

Aberg JA et al. 40th IDSA, Chicago, 2002, abstract 26.

% o

f pa

tient

s ac

hiev

ing

endp

oint

What intervention(s) would you recommend to improve his lipids?

A. Discontinue Kaletra, substitute atazanavir

B. Discontinue d4T, substitute tenofovir

C. Ask Mr. Burns to replace the donuts with granola in the vending machine

D. Start simvastatin

E. Start gemfibrozil

F. Nothing needs to be done, as studies have failed to document an increase in CAD in patients on HAART

Insulin Resistance

HIV/HAART Toxicities: Insulin Resistance

• PIs have direct effect on glucose metabolism1

• indinavir leads to decreased insulin sensitivity in both HIV-infected and uninfected subjects2

• amprenavir may not share this class effect3

• efavirenz, but not nevirapine, implicated as well4

• NRTIs also recently identified as risk factor5

• mechanism: ? inhibition of an insulin-regulated glucose transporter GLUT46

1. Dube MP et al. JAIDS 2000;27:130-4.2. Noor MA et al. AIDS 2001;15:4.3. Dube MP et al. Antivir Ther 2001;6(4):11. Abst 14.

4. Mehta et al, 9th CROI, 2002, Abstract 679.5. Brown TT et al. AIDS 2005, 19:1375–13836. Murata H et al. J Biol Chem 2000;275:251-4.

Currier et al, 9th CROI, February 2002, abstract 677-T

Bone Mineralization Disorders associated with HIV and/or

HAART

Osteopenia

Osteonecrosis

Study Sample Prevalence* Risk Factors

Carr, 2001

Australia

221 HIV+ men,

Wt. 70-75 kg

25% Lactate level

low weight

Huang, 2001

Boston, MA

41 HIV+ men, BMI 25

18 HIV- men, BMI 25

BMD reduced in HIV+ men w/ high visceral fat

Historical low weight;

high visceral fat

McDermott, 2001

New England

203 HIV+ men, BMI 24

62 HIV+ women, BMI 25

BMC reduced in men on HAART

HAART use and duration

Knobel 2001

Spain

58 HIV+ men, 22 HIV+ women, BMI 23 overall

100 HIV- controls, BMI 23

89% in HIV+

30% in HIV-

Weight, BMI

Nolan, 2001

Australia

183 HIV+ men

BMI 23-24

56% in PI-treated;

49% in PI-naïve

Low pre-HAART BMI;

Indinavir protective

Gold, 2002

Australia

110 HIV+ men

lean mass 57 kg

55% Age, lean body mass, duration of NRTI use

Mondy, 2003

St. Louis, MO

108 HIV+ men, 17 HIV+ women; BMI 25

46% BMI, smoking, wt loss, steroids

Arnsten, 2003

New York, NY

200 HIV+ women: BMI 28

205 HIV- women: BMI 32

30% in HIV+ 24% in HIV-

Age, race, BMI;

PI use > 1 year protective

Studies on Osteopenia in HIV

Adapted from Arnsten JH et al, 10th CROI, Boston 2003, Abstract 103

* combined prevalence of osteopenia and osteoporosis

Alendronate for HIV-associated osteopenia: 48 week results

• N=31 HIV-infected subjects on HAART with lumbar spine BMD t scores less than -1.0

• 87% male, 80% caucasian, 29% smokers, mean age 44yo; mean BMI 25kg/m2

• median CD4 count 561 cells/microliter; 84% had VL < 400 copies/mL

• randomized to alendronate 70mg weekly (n=15) or placebo (n=16)

• all patients received calcium 1g daily and vit D 400IU daily

• no serious adverse events

0

1

2

3

4

5

6

Spine Hip

placeboalendronate

p = 0.005

% c

han

ge f

rom

bas

elin

e in

BM

D

Mondy K et al. 10th CROI, Boston, 2003. Abstract 134.

p = NS

Avascular Necrosis of the Femoral Head

Higher Prevalence of Osteonecrosis

in HIV-Infected Adults • Screening MRIs performed on 339 asymptomatic

HIV-infected adults and 118 age- and sex-matched HIV-negative controls

• osteonecrosis of the femoral head identified in 15 of 339 (4.4%) HIV-infected patients compared to 0/118 controls (p<0.05)

• Comparison of HIV-infected patients with or without osteonecrosis showed no difference by age, sex, race, risk factor, CD4 cell count, viral load, antiretroviral therapy, blood lipids or CBC.

• The risk was increased for those who had received corticosteroids, lipid-lowering agents or testosterone.

Miller KD et al. Ann Intern Med 2002 Jul 2;137(1):17-25.

• Other studies of HIV-infected patients have found similar associations with steroid use and hyperlipidemia but not with the use of specific antiretroviral agents1,2

• Implication: consider this diagnosis in HIV-infected patients with shoulder, groin or hip pain

1. Scribner AN et al. JAIDS 2000;25:19-25.2. Glesby MJ et al. JID 2001;184:519-23.

Higher Prevalence of Osteonecrosis in HIV-Infected Adults

The End