Incidence of Insulin Resistance, the Metabolic Syndrome and Lipodystrophy in a 3 Year Cohort of HIV-Infected Patients Starting Antiretroviral Therapy in Côte d'Ivoire SP Eholié, K Lacombe, A Krain, ZDiallo, M Ouiminga, PCampa, O Bouchaud, E Bissagnene, PM Girard. LIP AFRI

Introduction * Natural history and risk factors for lipodystrophy have been well characterized through case reports and longitudinal cohort studies primarily in resource rich nations LD Prevalence (20-84%), incidence ( /100 PY) * Metabolic syndrome (MS) in patients on cART, further increasing the risk of age related chronic diseases in patients benefiting from a longer lifespan on antiretroviral therapy. MS prevalence (18% to 26%), incidence (8 -12/100 PY) depending on the definition used. *

Objectives * Primary objective * Secundary objective

PATIENTS AND METHODS * Study design: Three year prospective, multi-center, multinational longitudinal cohort study evaluating risk factors for the development of antiretroviral associated lipodystrophy (LPD) and metabolic syndrom (MS) and insuline resistance. * Patients: Patients presenting to the Treichville University Hospital in Abidjan, Côte d’Ivoire. * Inclusion criteria: documented HIV infection, age ≥ 16 yrs, of SSA origin, Karnofsky index ≥ 70, eligible to start cART in their country of residence and informed consent to participate in the study. * Exclusion criteria: clinical signs of LPD, pregnancy, body mass index (BMI) > 30 or 2.2 mmol/l or total cholesterol of > 5.5 mmol/l end stage renal, liver or cardiac disease.

Study design Inclusion 01/05/2005 – 31/01/2007 End of follow-up February 2010 J0 M12 M24 M36  Every 3 months: clinical + adherence monitoring  Every 6 months: clinical + biological + adherence monitoring  Every 12months: clinical + biological + adherence + insuline + dietétic  Closed prospective cohort  245 patients: Abidjan (176), Paris (69)

Method Definitions * Lipodystrophy 1)Definition 1 * Lipoatrophy: Fat loss in the checks, buttocks or extremities; or visible superficial veins * Lipohypertrophy: Gynecomastia or a bufffalo hump or abdominal obesity or truncal obesity * Combination of lipoatrophy and lipohypertrophy 1)Definition 2: care definition Presence of a moderate or severe grade of at least one of the above physcial exams findings

Method Definitions * HOMA calculated by multiplying the fasting serum insulin level by the fasting serum glucose level and then dividing by A score above 2 was considered to be elevated * Metabolic syndrom: ≥ 3 of the following 5 criteria - Waist circumference > 102 cm in males or > 88 cm in females; - Blood pressure ≥ 130/85 mmHG - Fasting triglycerides > 1.7 mmol/l; - HDL cholesterol < 1 mmol/l (M) or < 1.3 mmol/l (F); - Fasting blood glucose ≥ 6.1 mmol/l;

RESULTS

BASELINE CHARACTERISTICS Overall (N=245) Abidjan (N=176) Paris (N=69) Age (mean SD)36,2 (8,2)35,6 (7,4)37,8 (9,9) Sex ratio0,680,610,91 Delay for HIV diagnosis, month2,9 (1,7 – 10,0)2,7 (1,7 – 7,1)5,1 (2,1 – 32,0) Stage C CDC (n,%)48 (19,7)36 (20,3)12 (17,9) BMI, kg/m2 (mean, SD)21,4 (9,8)20,2 (3,4)23,8 (3,3) Caloric intake kcal HOMA Score0.71 (0.72)1.43 (1.31) CD4+ counts, mm3 (moy, SD)144 (100)119 (87)195 (112) Viral load log (moy, SD)5,1 (0,9)5,3 (0,8)4,5 (0,9) ART (n, %): - NNRTI - PI - 3TC - D4T - AZT 173 (70,9) 58 (23,8) 201 (82,4) 121 (49,6) 63 (25,8) 158 (89,2) 10 (5,7) 174 (98,3) 121 (68,4) 49 (27,7) 15 (22,4) 48 (71,6) 27 (40,3) 0 14 (20,9)

Incidence of insulin resistance, metabolic syndrom and lipodystrophy (rate/100 PY) Overall N=245 Abidjan N= 176 Paris N= 69 HOMA-IR > 247 (8.48)17 (3.95)30 (24.2) Metabolic syndrom31 (5.5)18 (4.3)13 (8.8) Lipodystrophy LD protocol LD Carr - Lipohypertrophy - Mixed LD - Lipoatrophy 125 (29.4) 39 (6.8) 23 (3.9) 13 (2.1) 3 (0.5) 89 (27.9) 19 (4.4) 6 (1.4) 11 (2.5) 2 (0.5) 36 (33.8) 20 (14.2) 17 (11.8) 2 (1.2) 1 (0.6)

Incidence of insulin resistance, metabolic syndrom and lipodystrophy (rate/100 PY) Overall N=245 Abidjan N= 176 Paris N= 69 P HOMA-IR > 247 (8.48)17 (3.95)30 (24.2)< Metabolic syndrom31 (5.5)18 (4.3)13 (8.8)0.06 Lipodystrophy LD protocol LD Carr - Lipohypertrophy - Mixed LD - Lipoatrophy 125 (29.4) 39 (6.8) 23 (3.9) 13 (2.1) 3 (0.5) 89 (27.9) 19 (4.4) 6 (1.4) 11 (2.5) 2 (0.5) 36 (33.8) 20 (14.2) 17 (11.8) 2 (1.2) 1 (0.6) 0.2 <

Survival rates of patients with CARR defined lipodystrophy over time, by study site 14.2/100 PY 4.4/100 PY Lipodystrophy : 19 (4.4/100 PY) Lipohypertrophy: 6 (1.4/100 PY) Mixed LD: 11 (2.5/100 PY) Lipo-Atrophy: 2 (0.5% 100 PY)

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Survival rates of patients with metabolic syndrome over time, by study site 4.3/100 PY 8.8/100 PY

Survival rates of patients with an elevated HOMA-IR over time, by study site 3.95/100 PY 24.2/100 PY

Predictive factors for lipodystrophy, metabolic syndrom and insulin resistance Outcomes Univariate Hazard ratio P Multivariate Adjusted HR P * Lipodystrophy - BMI ≥ 25 kg/m 2 - PI > 18 months Saquinavir Lopinavir 4.58 ( ) ( ) ( ) < ( ) ( ) ( ) 0.6 * Metabolic syndrom - Gender (F) - BMI ≥ 25 kg/m Nelfinavir > 18 M 12.8 ( ) ( ) < ( ) ( ) ( ) < ( ) 0.06 * HOMA > 2 - Gender (F) - VL > copies - Saquinavir > 18 M 0.5 ( ) ( ) ( ) ( ) ( ) ( ) 0.01

Conclusion * Increase risk of LD, SM and insuline resistance after 3 years follow-up; * Incidence rates lower than data observed in developped countries; * Further research needs to be done to untangle socio-environmental factors resulting in the differing incidences of metabolic complications.

ACKNOWLEDGEMENTS * Coordinators and investigators of LIPO-AFRI study * Physicians, nurses of Lipo-Afri study * Patients involved in LIPO-AFRI study * Dr Maryam Kassambara Sow * Dr Elie Bankineza * Fundation Bristol Myer Squibb, Program Secure the Future

AmesegnalehuThank you