HIV-Associated HIV-Associated Lipodystrophy: Lipodystrophy:

Modifiable Risk Factors Modifiable Risk Factors in Croatian Patientsin Croatian Patients

Christine M. Stanley, B.A. Christine M. Stanley, B.A. †

Drago TurDrago Turččinov, M.D.*inov, M.D.*

George Rutherford, M.D. George Rutherford, M.D. †

Thomas E. Novotny, M.D. Thomas E. Novotny, M.D. †

Josip Begovac, M.D.*Josip Begovac, M.D.*

†University of California San Francisco*University Hospital of Infectious Diseases, Zagreb,

Croatia

Lipohypertrophy: Lipohypertrophy: dorsocervical dorsocervical fat pad, neck circumference, fat pad, neck circumference, breast, abdominal fatbreast, abdominal fat

Lipodystrophy and HIV/AIDSLipodystrophy and HIV/AIDS

Lipoatrophy:Lipoatrophy: loss of fat from loss of fat from cheeks, arms, thighs, cheeks, arms, thighs, buttocks, shoulders buttocks, shoulders

Anti-retroviral (ARV) related lipodystrophyAnti-retroviral (ARV) related lipodystrophy: :

5-30% of people on protease inhibitors5-30% of people on protease inhibitors

Also non-nucleoside reverse transcriptase Also non-nucleoside reverse transcriptase inhibitors (NNRTI)inhibitors (NNRTI)

Risk Factors for Lipodystrophy Risk Factors for Lipodystrophy (LD)(LD)

Non-modifiableNon-modifiable Increasing ageIncreasing age Female genderFemale gender Greater duration of ARVGreater duration of ARV Greater body weight before ARVGreater body weight before ARV

ModifiableModifiable SmokingSmoking Diet: Smaller intake of total protein Diet: Smaller intake of total protein

and total dietary fiber while taking and total dietary fiber while taking ARVARV

Study Question: Could diet Study Question: Could diet decrease the risk of LD in decrease the risk of LD in HIV/AIDS patients on ARVs?HIV/AIDS patients on ARVs?

Mediterranean Diet:Mediterranean Diet: high intake of legumes, fruits, vegetables, high intake of legumes, fruits, vegetables,

nuts, cereals and olive oilnuts, cereals and olive oil moderate intake of fishmoderate intake of fish low to moderate intake of dairy productslow to moderate intake of dairy products low intake of meat and poultrylow intake of meat and poultry moderate intake of alcoholmoderate intake of alcohol

Population-based Greek study found Population-based Greek study found Mediterranean diet protective against Mediterranean diet protective against death due to coronary heart disease and death due to coronary heart disease and cancer.cancer.

Hypothesis:Hypothesis: HIV/AIDS patients HIV/AIDS patients adherent to adherent to Mediterranean diet Mediterranean diet will have lower LD will have lower LD risk;risk;

Setting:Setting: One clinic in One clinic in Zagreb treats all HIV Zagreb treats all HIV patients in Croatia;patients in Croatia;

Target group:Target group: Patients from Patients from diverse diverse geographical areas geographical areas with differing dietswith differing diets

Croatia: Croatia: A Mediterranean and A Mediterranean and Central European CountryCentral European Country

136 patients from HIV clinic of Fran 136 patients from HIV clinic of Fran Mihalavic Infectious Disease Hospital in Mihalavic Infectious Disease Hospital in Zagreb, treated with ARV for at least Zagreb, treated with ARV for at least one year;one year;

LD assessed using patient self-report LD assessed using patient self-report and confirmation by physical exam;and confirmation by physical exam;

Metabolic data and body Metabolic data and body measurements obtained on all measurements obtained on all patients.patients.

MethodsMethods

Measuring Dietary Measuring Dietary AdherenceAdherence

Food questionnaire included 150 food and Food questionnaire included 150 food and beverage items;beverage items;

Usual dietary intake during the preceding Usual dietary intake during the preceding year was calculated:year was calculated:

5 Beneficial categories: vegetables, 5 Beneficial categories: vegetables, legumes, fruits and nuts, cereals and legumes, fruits and nuts, cereals and fishfish

3 Detrimental categories: meat, 3 Detrimental categories: meat, poultry, dairypoultry, dairy

Moderate alcohol consumption Moderate alcohol consumption considered beneficialconsidered beneficial

A ten-point adherence scale dichotomized A ten-point adherence scale dichotomized into:into: < 4 points = low adherence< 4 points = low adherence 4 points = medium and high adherence4 points = medium and high adherence

ResultsResults

41% of participants had moderate to 41% of participants had moderate to severe lipoatrophy; severe lipoatrophy;

32% of participants had moderate to 32% of participants had moderate to severe lipohypertrophy;severe lipohypertrophy;

Mediterranean diet score of Mediterranean diet score of 4 was 4 was independently associated with a lower independently associated with a lower risk of lipohypertrophy.risk of lipohypertrophy.

Risk Factors for LDRisk Factors for LD

OR 95%CI P Lipoatrophy

Gender Male Female

0.33 1.00

0.13-0.86

0.023

Stavudine use Yes No

3.99 1.00

1.72-9.28

0.001

Duration of HAART (per 12 months)

1.47 1.17-1.85 0.001

Lipohypertrophy

Mediterranean diet score <4 ?4

1.00 0.31

0.12-0.77

0.012 Gender Male Female

0.09 1.00

0.03-0.26

<0.001

Known duration of HIV infection before start of HAART (per 12 months)

1.17

1.05-1.31

0.005

Duration of HAART < 25 months ? 25 months

1.00 5.49

1.42-21.31

0.014

LD and Food CategoriesLD and Food Categories

Men without LD Men without LD (n=108) consumed (n=108) consumed more fish more fish (p=0.026), less (p=0.026), less meat (p=0.028) meat (p=0.028) and less vegetable and less vegetable oils (p=0.024). oils (p=0.024). 77% of men 77% of men without LD vs 47% without LD vs 47% with LD frequently with LD frequently consumed olive oil consumed olive oil (p=0.002).(p=0.002).

0

20

40

60

80

100

120

140

Med

ian

food

con

sum

ptio

n (g

/day

)

Lipodystrophy No Lipodystrophy

Meat Fish Vegetable Oils

Dietary intake from 108 men in relation to lipodystrophy

LD is common, progressive syndrome LD is common, progressive syndrome in HIV/AIDS patients taking ARV;in HIV/AIDS patients taking ARV;

Changes in fat distribution persist Changes in fat distribution persist after discontinuation of ARV;after discontinuation of ARV;

LD may be disfiguring and LD may be disfiguring and stigmatizing;stigmatizing;

Because of cost and availability, Because of cost and availability, patients may not have option to patients may not have option to change treatment.change treatment.

Discussion: Discussion: LipodystrophyLipodystrophy

DietDiet Adherence to Mediterranean diet Adherence to Mediterranean diet

associated with decreased LD risk;associated with decreased LD risk; Consuming more fish, less meat, and less Consuming more fish, less meat, and less

vegetable oil associated with lower LD risk;vegetable oil associated with lower LD risk; Consuming olive oil associated with lower Consuming olive oil associated with lower

LD risk.LD risk.

SmokingSmoking Former or current smokers had higher risk of Former or current smokers had higher risk of

lipoatrophy (p=0.042)lipoatrophy (p=0.042)

ConclusionsConclusions

Cross-sectional designCross-sectional design Prospective randomization not possibleProspective randomization not possible Difficult to infer causality due to multiple confoundersDifficult to infer causality due to multiple confounders

Study LimitationsStudy Limitations

Results specific to this patient group and may Results specific to this patient group and may not be generalizable;not be generalizable;

Questionable accuracy of retrospective dietary Questionable accuracy of retrospective dietary information; information;

LD determined by self-report and physical exam.LD determined by self-report and physical exam.

Dr. Josip Begovac, Christine Stanley, Sarah Gertler, Nancy Gertler

Plitvice Lakes National Park , Croatia