I5 TH KAP ANNUAL SCIENTIFIC CONFERENCE PROGRAMME Kisumu, Kenya

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2 Lopinavir/ritonavir+Tenofovir/Emtricitabine is Associated With Less Favorable Changes in Lipids Compared to Nevirapine+Tenofovir/Emtricitabine in Women Initiating ART in sub Saharan Africa: A5208 ( OCTANE ) I5 TH KAP ANNUAL SCIENTIFIC CONFERENCE PROGRAMME Kisumu, Kenya Douglas Shaffer, MD, MHS, FACP Kenya Medical Research Institute/Walter Reed Project HIV Program Kericho, Kenya

3 Case Presentation ID: 52 y/o female w/ CD4=102 cells/μl presents to HIV clinic for ART initiation HPI/Cc: 3 4 month h/o heartburn & chest pain usually after breakfast; currently with heartburn PMH: Tb, PUD, recurrent UTI Rx 2 0 active bladder, LMP=42 y/o Rx: TMP/SMX, MVI, omeprazole, & ciprofloxacin SH: busaa qd, cigarettes prn, 3 healthy children (12 20 y/o), widowed (husband died 2 0 HIV), works in garden daily Work up/results?

4 Diagnostic Evaluations CD4 = 102 cells/μl HgB = 13.1 gm/dl ( ) Cr = 185 umol/l (55 102) ALT = 30.2 U/L ( ) Urine dip: unavailable BP = 165/99 mmhg (normal/low risk < /80 90) BMI = 33 kg/m 2 (obese > 30.0) Cholesterol = 7.1 mmol/l ( ) LDL = 4.2 mmol/l ( ) HDL = 0.8 mmol/l ( ) Triglycerides = 3.0 mmol/l ( ) Glucose = 8.2 mmol/l ( )

5 Chest X Ray

6 Electrocardiogram

7 Diagnosis Acute inferior wall myocardial infarction in an HIV infected, post menopausal, female with dyslipidemia, hyperglycemia, and high blood pressure

8 Background Attention to cardiovascular risk factors (CVRFs) in PLWHAs receiving ART in sub Saharan Africa is important with increased focus on comprehensive, long term disease management. Limited, long term prospective data currently exist regarding CVRFs in HIV infected women receiving ART in sub Saharan Africa, with virtually no randomized, controlled trial data by ART regimens. The Optimal Combination Therapy After Nevirapine Exposure (OCTANE) study provides an opportunity to compare CVRFs between women receiving LPV/r and NVP based ART.

9 OCTANE* Study Design (Optimal Combination After Nevirapine Exposure) + SD NVP SD NVP 1:1 1:1 TDF+FTC+ NVP TDF+FTC+ LPV/RTV TDF+FTC+ NVP TDF+FTC+ LPV/RTV Endpoints: 1. Virologic failure 2. Death HIV+ female > 18 y/o CD4 < weeks, after last participant has been enrolled Trial 1: superiority study (n=241) Trial 2: non inferiority/equivalence study (n=500) 741 women enrolled in South Africa, Zimbabwe, Botswana, Malawi, Uganda, Kenya, & Zambia * Lockman S, et al. The OCTANE Study (ACTG A5208). N Engl J Med Oct 14;363(16):

10 CVRF Secondary Analyses Data from trial 1 and Trial 2 (n=741) Restricted to the period of time women remained on initial, randomized ART CVRFs from follow up weeks 48 and 96 Lipids obtained regardless of fasting status Descriptive statistics used (mean (SD) or percent) for baseline characteristics General linear model used to calculate unadjusted and adjusted mean changes (95% CI) 48 & 96 weeks after ART World Health Organization (WHO) and/or National Institutes of Health (NIH) criteria used for assigning clinical categories

11 Baseline Characteristics* NVP (370) LPV/r (n=371) Age (years) 33.5 (7.0) 33.4 (7.2) Baseline CD4 (cells/mm 3 ) (65.8) (68.3) HIV 1 RNA (log 10 (copies/ml)) 5.0 (0.7) 5.1 (0.7) Cholesterol (mg/dl) (32.2) (31.4) Cholesterol < 200 mg/dl 97.8% 97.0% HDL (mg/dl) 34.3 (14.6) 34.0 (13.2) HDL < 40 mg/dl 70.8% 70.5% SBP (mmhg) (16.2) (15.4) DBP (mmhg) 73.2 (11.8) 72.8 (10.6) BP < 140/90 mmhg 89.5% 92.1% BMI (kg/m 2 ) 23.7 (5.0) 23.5 (4.7) BMI > 25 kg/m % 30.5% * Data available from > 96% of participants for each variable presented

12 Week 48 & 96 CVRFs* Chol (mg/dl) HDL (mg/dl) TC/HDL ratio SBP (mmhg) DBP (mmhg) BMI (kg/m 2 ) Week N NVP (n=370) Mean Change Standard Error N LPV/r (n=371) Mean Change Standard Error Adjusted Analysis * Difference in Mean (95% CI) P value ( 13.1, 3.3) ( 14.1, 1.6) (3.9, 8.2) < (2.9, 8.3) < ( 1.1, 0.3) ( 0.8, 0.1) (1.0, 4.9) (1.0, 6.1) (1.7, 4.6) < (2.0, 5.6) < (0.3, 1.0) (0.3, 1.4) * Adjusted for baseline risk factor and prior single dose NVP

13 Baseline to Week 48 & 96 Categorical Clinical Changes in CVRFs* Week NVP (n=370) LPV/r (n=371) Cholesterol (mg/dl) HDL (mg/dl) TC/HDL ratio SBP/DBP (mmhg) BMI (kg/m 2 ) <200 to >200 <200 to > % 6.5% % 9.1% <40 to >40 <40 to > % 15.4% % 13.5% < 4.0 to > 4.0 < 4.0 to > % 10.5% % 12.2% <139/<89 to >140/>90 <139/<89 to >140/> % 5.7% % 7.3% <24.99 to >25.0 <24.99 to > % 11.3% % 3.7% * Only selected categories of clinical concern shown NVP & LPV/r significantly different for all but BMI

14 Conclusions LPV/r+TDF/FTC was associated with less favorable changes in lipids (greater increase in cholesterol, lesser increase in HDL, and smaller decrease in TC/HDL) but smaller increases in BMI and BP compared to NVP+TDF/FTC in women initiating ART in sub Saharan Africa. The long term clinical significance of these changes is unknown. Awareness and management of CVRFs will take on larger roles in chronic disease management of PLWHAs in sub Saharan Africa.

15 Acknowledgements KEMRI/WRP Kericho Moi University Eldoret Fred Sawe Abraham Siika Hellen Ngeno Pricilla Chepkorir Kericho District Hospital Moi Teaching and Referral Hospital Eunice Obiero Sylvester Kimaiyo Clinic team Clinic team OCTANE teams in South Africa, Zimbabwe, Botswana, Malawi, Uganda, & Zambia CVRF analyses presented at CROI 2011: Yajing Bao, Agnes Moses, Fredrick Sawe, Yu Zheng, Michael Hughes, Shahin Lockman, and Judith Currier OCTANE Study Volunteers