HIV-Associated Lipodystrophy: Modifiable Risk Factors in Croatian Patients Christine M. Stanley, B.A. † Drago Turčinov, M.D.* George Rutherford, M.D. † Thomas E. Novotny, M.D. † Josip Begovac, M.D.* †University of California San Francisco *University Hospital of Infectious Diseases, Zagreb, Croatia

Lipodystrophy and HIV/AIDS Anti-retroviral (ARV) related lipodystrophy: 5-30% of people on protease inhibitors Also non-nucleoside reverse transcriptase inhibitors (NNRTI) Lipohypertrophy: dorsocervical fat pad, neck circumference, breast, abdominal fat Lipoatrophy: loss of fat from cheeks, arms, thighs, buttocks, shoulders

Risk Factors for Lipodystrophy (LD) Non-modifiable Increasing age Female gender Greater duration of ARV Greater body weight before ARV Modifiable Smoking Diet: Smaller intake of total protein and total dietary fiber while taking ARV Hendricks et al 2003 Am Journal Clinical Nutrition, case control study of 47 cases

Study Question: Could diet decrease the risk of LD in HIV/AIDS patients on ARVs? Mediterranean Diet: high intake of legumes, fruits, vegetables, nuts, cereals and olive oil moderate intake of fish low to moderate intake of dairy products low intake of meat and poultry moderate intake of alcohol Population-based Greek study found Mediterranean diet protective against death due to coronary heart disease and cancer. Population based (22,043 participants) prospective study of this diet in the Greek population was published in 2003 Found that a higher degree of adherence to the diet was associated with a reduction in total mortality, inverse association between diet adherence and death due to coronary heart disease and death due to cancer

Croatia: A Mediterranean and Central European Country Hypothesis: HIV/AIDS patients adherent to Mediterranean diet will have lower LD risk; Setting: One clinic in Zagreb treats all HIV patients in Croatia; Target group: Patients from diverse geographical areas with differing diets Approximately 450 people identified as having HIV in Croatia

Methods 136 patients from HIV clinic of Fran Mihalavic Infectious Disease Hospital in Zagreb, treated with ARV for at least one year; LD assessed using patient self-report and confirmation by physical exam; Metabolic data and body measurements obtained on all patients. Severity and number of signs was used to categorize patients as having lipoatrophy and/or lipohypertrophy Metabolic characteristics included HDL, LDL and total cholesterol. Body measurements included waist-to-hip ratio, change in BMI, weight prior to HAART

Measuring Dietary Adherence Food questionnaire included 150 food and beverage items; Usual dietary intake during the preceding year was calculated: 5 Beneficial categories: vegetables, legumes, fruits and nuts, cereals and fish 3 Detrimental categories: meat, poultry, dairy Moderate alcohol consumption considered beneficial A ten-point adherence scale dichotomized into: < 4 points = low adherence  4 points = medium and high adherence Sex-specific median cutoffs

Results 41% of participants had moderate to severe lipoatrophy; 32% of participants had moderate to severe lipohypertrophy; Mediterranean diet score of  4 was independently associated with a lower risk of lipohypertrophy.

Risk Factors for LD 56 with lipoatrophy, 44 with lipohypertrophy,  56 with lipoatrophy, 44 with lipohypertrophy, Stavudine is a Nucleotide reverse transcriptase inhibitor

LD and Food Categories Men without LD (n=108) consumed more fish (p=0.026), less meat (p=0.028) and less vegetable oils (p=0.024). 77% of men without LD vs 47% with LD frequently consumed olive oil (p=0.002). Meat Fish Vegetable Oils Dietary intake from 108 men in relation to lipodystrophy

Discussion: Lipodystrophy LD is common, progressive syndrome in HIV/AIDS patients taking ARV; Changes in fat distribution persist after discontinuation of ARV; LD may be disfiguring and stigmatizing; Because of cost and availability, patients may not have option to change treatment.

Conclusions Diet Adherence to Mediterranean diet associated with decreased LD risk; Consuming more fish, less meat, and less vegetable oil associated with lower LD risk; Consuming olive oil associated with lower LD risk. Smoking Former or current smokers had higher risk of lipoatrophy (p=0.042)

Study Limitations Cross-sectional design Prospective randomization not possible Difficult to infer causality due to multiple confounders Results specific to this patient group and may not be generalizable; One time point for assessment of lipodystrophy Questionable accuracy of retrospective dietary information; LD determined by self-report and physical exam.

Plitvice Lakes National Park , Croatia Dr. Josip Begovac, Christine Stanley, Sarah Gertler, Nancy Gertler