1. Assessment of cardiovascular risk in a 3-year- cohort of HIV-infected patients of Sub-Saharan origin living in France or Côte d’Ivoire and starting antiretroviral therapy. SP Eholié, K Lacombe, A Krain, Z Diallo, M Ouiminga, P Campa, O Bouchaud, E Bissagnéné, PM Girard LIP AFRI

2. INTRODUCTION (1) HIV-infected patients of Sub-Saharan African (SSA) origin are increasingly accessing combination antiretroviral therapy (cART) in their countries of origin and adoption; Cardiovascular disease (CVD) prevention and treatment is of increasing importance with longer life spans on cART; Most studies on cardiovascular disease risk (CVR) in HIV-infected patients on cART are primarily Caucasian cohorts in resource rich nations.

3. INTRODUCTION (2) The Data collection of Adverse Effects of Anti-HIV Drugs Study (DAD) Cohort study group recently published a CVR prediction equation for HIV infected patients on cART; The World Health Organization (WHO) and International Society of Hypertension (ISH) developed field based CVR prediction charts, based on the patients’ WHO region of origin. These charts do not take into account HIV infection or cART use; The two CVR prediction equations were compared using data from patients who participated in a three year completed cohort of HIV infected patients of SSA origin living in France or Côte d’Ivoire.

4. Objectives 1.To quantify the estimated 10 year cardiovascular disease risk (CVR) in HIV- infected patients of Sub-Saharan origin starting antiretroviral therapy. 2.To compare the differences in the 10 year cardiovascular risks in the populations at the two different countries of residence. 3.To compare the 10 year cardiovascular disease risk as estimated by the DAD equation and the field based WHO risk prediction charts.

5. 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). * Patients: Patients presenting to one of three University Hospital Centers in Paris, France (Saint Antoine, Avicenne and Tenon) and at 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.

6. 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)

7. Methodology Assessment of cardiovascular risk * Framinghams’ Score: age, presence or absence of diabete, presence or absence of smoking, blood pressure categories and LDL cholesterol (Wilson PWF,Circulation 1998) * Equation of DAD Study Group: Framingham + exposure to indinavir, lopinavir and presence/absence of abacavir in the current c-ART (model used to estimate 12 months CV risk) * 10 years Prediction of WHO/ISH CVR : Sub regional epidemiological speficities + following risk factors: gender, Systolic blood pressure, smoking, diabete type 2, Total cholesterol

8. PATIENTS AND METHODS Calculating risk scores: 1.The 10 year DAD cardiovascular disease risk (CVR) was calculated using the DAD equation (Figure 1) Definition of cardiovascular disease (CVD): stroke, endarterectomy of the carotid artery, any invasive coronary artery procedure, myocardial infarction or death due to coronary heart disease. Factors in DAD equation: age, sex, systolic blood pressure (SBP), smoking status, family history of CVD, total and HDL cholesterol, diabetes, IDV, LPV/r and ABC exposure (Figure 2). DAD equation for the risk of CVD, CND or MI

9. PATIENTS AND METHODS The 10 year WHO/ISH CVR was obtained by creating a Stata TM 10.0 based model of the risk prediction charts (Figure 3). CVR calculated for each participant at baseline and at months 12, 24 and 36. Definition of cardiovascular event: fatal or non-fatal stroke or myocardial infarction. Factors in WHO/ISH model: patient’s WHO African sub-region, gender, age group, SBP, smoking status, diabetes and total cholesterol. Patients younger than 40 years of age were put into the 40 – 49 age group.

10. RESULTS

11. BASELINE CHARACTERISTICS Overall (N=245) Abidjan (N=176) Paris (N=69) LFU (n, %)32 (13,1)24 (13,6)8 (11,9) Age (mean SD)36,2 (8,2)35,6 (7,4)37,8 (9,9) Sex ratio0,680,610,91 Delay for HIV diagnosis, month s(med, IQR) 2,9 (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)20,5 (2,5)23,8 (3,3) CD4+ counts, mm3 (moy, SD)144 (100)124 (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)

12. Paris: 2.93% Abidjan: 2.45% Ten years cardiovascular risk diseases by cohort Paris: 2.43% Abidjan: 1.37% P<0.001 P=0.6

13. Survival probability of patients with a fifty percent increase in 10-year DAD Cardiovascular Disease Risk (CVR) There were no reported cases of cardiovascular disease (MI, CVA) during the three years of follow up.

14. Ten-year estimated WHO/ISH cardiovascular disease risk in HIV positive patients of Sub-saharan African origin on cART.

15. CONCLUSION The DAD CVR equation demonstrated a small but significantly different risk of 10-year CVR before cART initiation between the two study sites, becoming non significant at the end of follow up. The WHO 10-year CVR prediction charts, while very applicable in the field, gave less precise figures on 10 year CVR disease risk and does not take into account HIV infection or cART. As there were no reported cases of cardiovascular disease during follow up, no determinants of CVR could be evaluated but determinants such as country of residence and cART regimen would be of interest. More extensive follow up is needed to know which cardiovascular prediction model would be most useful and accurate for HIV patients of Sub-Saharan origin on cART.

16. 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

17. AmesegnalehuThank you