1. Enrollment into Open-Label Phase of TDF2 PrEP Study, Botswana, 2013 Chirwa LI 1, Taylor AW 2, Williams TS 2,3, Henderson FL 2, Kasonde M 1, Mutanhaurwa R 1, Matlhaba O 1, Hageman K 2, Casillas P 1, Samandari T 2 1. Centers for Disease Control and Prevention, Gaborone and Francistown, Botswana; 2. Centers for Disease Control and Prevention, Atlanta, GA; 3. ICF Macro, Atlanta, GA The findings and conclusions in this presentation are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

2. Background TDF2 Study (2007–2009) –1219 HIV-negative heterosexual young adults in Botswana (1563 person-years, PY) –Randomized 1:1 to TDF/FTC or placebo –1.2 infections per 100 PY in TDF/FTC vs 3.1/100 PY in placebo group –62% protective efficacy (Thigpen et al NEJM. 2012 Aug 2;367(5):423-34)

3. Background TDF2 Open-Label Extension (OLE) –Protocol: if efficacy demonstrated, provide TDF/FTC for TDF2 participants for 12 months –Further safety, effectiveness, risk and adherence data We report: –Baseline characteristics –Preliminary visit adherence –Preliminary safety

4. Methods Screening occurred from Feb - May 2013 Inclusion criteria included: –Former TDF2 participants –Provided informed consent –Normal serum creatinine/phosphorus –If female, willing to use hormonal contraceptive Exclusion criteria included: –HIV infection –Pregnancy or breastfeeding –Other clinical condition that made the participant unsuitable for enrollment

5. Methods Study Procedures –Monthly follow-up visits 30-day supply of TDF/FTC dispensed at each visit 2 finger-stick rapid HIV tests (Ag/Ab, HIV 1/2) If female, pregnancy testing Adherence counseling –Quarterly visits included HIV EIA Safety labs Risk reduction counseling –Retention strategies included SMS text messaging and phone calls –No reimbursement Study Status –Last exit visits July 2014

6. 1219 Former TDF2 participants 1219 Former TDF2 participants 582(48%) able to contact and scheduled for screening 334 (57%) attended screening 334 (57%) attended screening 67 (20%) were ineligible 67 (20%) were ineligible 267 (80%) were eligible to start TDF/FTC 267 (80%) were eligible to start TDF/FTC 229 (86%) started TDF/FTC 229 (86%) started TDF/FTC Recruitment, Screening, and Enrollment of TDF2 Open Label Extension Participants Reasons for Ineligibility: -Did not consent -Had no interest/no time -Pregnant/breastfeeding -Had abnormal labs -Were HIV-positive Reasons for Ineligibility: -Did not consent -Had no interest/no time -Pregnant/breastfeeding -Had abnormal labs -Were HIV-positive 38 (14%) did not start TDF/FTC 38 (14%) did not start TDF/FTC

7. Table 1. Selected characteristics of enrolled TDF2 Open Label Extension study participants, 2013-2014 Started DrugDid Not Start Drug N=229N=38P-value n (%) Site0.50 Gaborone134 (58.5)20 (52.6) Francistown95 (41.5)18 (47.4) Gender0.23 Female102 (44.5)13 (34.2) Male127 (55.5)25 (65.8) Median Age (IQR)30 (28, 34)29 (27, 31)0.13 Education Level0.74 Primary and below4 (2)1 (2.6) Secondary141 (61)21 (55.3) Post-Secondary84 (37)16 (42.1) Marital Status0.13 Single163 (71.2)25 (65.8) Married18 (7.9)0 (0) Cohabitating37 (16)10 (26.3) Separated/widowed11 (4.9)3 (7.9) Employment Status0.37 Employed178 (77.7)27 (71) Unemployed51 (22.3)11 (29) Median Income(IQR), USD*193 (114,398)205 (100,512)0.86 Median Travel Time (IQR)30 (20,55)30 (20,60)0.96 Had an HIV Test since TDF2212 (92.6)33 (86.8)0.23 *Botswana Pula converted to USD using exchange rate of 8.79. Results

8. Table 2. Participants' motivations for TDF2 Open Label Extension study participation, 2013-2014 Started Drug Did Not Start Drug N=229N=38 n (%) P-value Feels at risk183 (80)24 (63.2)0.02 Feels partner is at risk156 (68.1)18 (47.4)0.01 Partner is HIV positive30 (13)3 (7.9)0.59 Does not know partners HIV status 91 (39.7)16 (42.1)0.78 Inconsistent condom use113 (49.3)18 (47.4)0.82 Multiple sex partners109 (47.6)15 (39.5)0.35 Exchanges sex10 (4.4)3 (7.9)0.41 Family encouraged54 (23.5)5 (13.2)0.21 Friend encouraged34 (14.9)2 (5.3)0.13 Sex partner encouraged78 (34)9 (23.7)0.21 Results

9. Retention –Of the 229 participants who started TDF/FTC, 125 (54%) completed 12 months of follow-up

10. Results Table 3. Baseline HIV risk perception by study completion for enrolled participants, TDF2 Open Label Extension, 2013-2014 Completed 0-9 months Completed 10-12 months P-Value Perceived HIV risk in the past 6 months, n (row %) 0.03 Low Risk61 (44.9)75 (55.2) High or Medium Risk28 (30.8)63 (69.2) Perceived HIV risk in the next 6 months, n (row %) 0.64 Low Risk75 (40)113 (60) High or Medium Risk14 (35.9)25 (64.1)

11. Severe Adverse Events 10 Severe Adverse Events (SAE) reported Involving total of 8 participants Resolution of SAE SAEs reported to CDC Spontaneous resolution Temporary hold Permanent discontinuation Unresolved at study exit Total Hypophosphatemia, Grade 3 132 6 Hyperamylasemia, Grade 3 1113 Hypercreatininemia, Grade 1 1 1 Total 342110

12. Conclusions Higher risk perception among those starting TDF/FTC compared with those not starting Participants reporting higher baseline HIV risk were more likely to complete the study TDF/FTC was safe and well tolerated

13. Lessons Learned High Interest in PrEP –79% of those contacted scheduled screening visit to learn more –86% of those who screened eligible began PrEP Logistical considerations –Delay in study start –Monthly visits –Lack of reimbursement

14. Next Steps Motivations and risk behaviors Drug levels and adherence Qualitative substudy –Reasons for screening losses –Reasons for drop-out –Experience in study

15. Ke a leboga! TDF2 and OLE participants Botswana MOH Gilead Sciences, Inc. CDC –Chuck Rose –Lisa Harper –Michael Thigpen –Lynn Paxton –Paula Casillas MINISTRY OF HEALTH REPUBLIC OF BOTSWANA TDF2 OLE Study Staff Joseph, Tshepang Ndungo, Josephine Moeletsi, Febby Keatlhotswe, Mothusi Sebonego, Wandani Kabelo, Tshepo Manyiwa, Early Mogatle, Karen Mokanyane, Onalenna Lekoko, Molemane Simon, Boikhutso Gabanthate, Rose Lefhoko, Abigail Majaye, Gene Seabelo, Baganetsi Makovore, Vongai Molosiwa, Molefhi

16. Author Contact Information Lovemore Ian Chirwa, MBBS, MPhil –hos2@cdc.gov –Tel: +267 2415222 Allan W. Taylor, MD, MPH –ataylor2@cdc.gov –+1 404-639-6120