Characteristics and Oral PrEP Adherence in the TDF2 Open-Label Extension in Botswana Henderson FL 1, Taylor AW 1, Chirwa LI 2,Williams TS 1,3, Borkowf CB 1, Kasonde M 2, Mutanhaurwa R 2, Matlhaba O 2, Hageman K 1, Casillas P 2, Samandari T 1 1. Centers for Disease Control and Prevention, Atlanta, GA 2. Centers for Disease Control and Prevention, Gaborone and Francistown, Botswana 3. ICF Macro, Atlanta, GA National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention Division of HIV/AIDS Prevention The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

Background  TDF2 Study, 2007–2010  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*  TDF2 Open-Label Extension (OLE),  Provide TDF/FTC for TDF2 participants for 12 months  Assessed safety, effectiveness, behavioral risk compensation and adherence *Thigpen et al NEJM Aug 2;367(5):423-34

Methods  Screening occurred from February May 2013  Monthly visits  30-day supply of TDF/FTC dispensed with adherence counselling  Dual rapid HIV test (Ag/Ab, HIV 1/2)  Pregnancy testing (female)  Provided condoms  Quarterly visits  HIV EIA (Ag/Ab, HIV 1/2) & safety labs  Risk reduction counseling  Retention strategies included SMS text messaging and phone calls  No reimbursement provided

 Post Study: Tenofovir levels were measured using dried blood spot cards  Dried blood spot cards were collected monthly  120 (52%) out of 229 participants were tested at 5 time points during follow-up  Sampling method focused on a longitudinal view of adherence Methods NMonths Tested Group 1301, 2, 5, 8, 11 Group 2301, 3, 6, 9, 12 Group 3301, 4, 7, 10, 12 Group 4301, months around missed visit(s)

RESULTS

Screening, Enrollment, and Follow-up of TDF2 OLE Participants, Botswana,  Observed person-years in TDF2 OLE  Last participant exit occurred in July 2014

Factors Associated with Not Completing TDF2 OLE, Botswana, CharacteristicsUnadjusted Risk Ratio (RR)95% CIP Value Gender Female Male 1.6 Ref (1.2, 2.3)<0.01 Adverse event* No Yes 2.1 Ref (1.3, 3.4)<0.01 *Definitely or possibly related adverse events experienced during the entire length of follow-up  Factors that were not associated but were examined in the univariate model:  Enrollment Site  Age  Education  Marital Status  Employment status  Travel time to clinic  Sex partners in the past 3 months  Condomless sex acts in the past 3 months

Mean Number of Sex Partners in Past 30 Days, TDF2 OLE, Botswana,

Mean Number of Condomless Sex Acts in Past 30 Days TDF2 OLE, Botswana,

Extracellular TFV Detectability* TDF2 OLE, Botswana, *n=120 participants; Lower limit of detection = 5 ng/mL

Factors Associated with Extracellular TFV Detectability* TDF2 OLE, Botswana, CharacteristicsAdjusted RR95% CIP Value Gender Female Male 0.91 Ref (0.86, 0.96)<0.001 Condomless Sex Acts 0 acts > 1 acts 0.95 Ref (0.91, 1.00)0.06 Sex Partners in the Past 30 Days 0 sex partners 1 sex partner >2 sex partners Ref (0.91, 1.08) (0.93, 1.04) Enrollment Site Gaborone Francistown 1.07 Ref (1.01, 1.12)0.01 *n=120 participants; Lower limit of detection = 5 ng/mL

Association Between Self Reported Adherence and Extracellular TFV Detectability* TDF2 OLE, Botswana, Noted an association present between self- reported adherence and detectable drug, p < *n=120 participants; Lower limit of detection = 5 ng/mL

Self Reported Adherence in Past 3 Days TDF2 OLE, Botswana, Overall, 87% of participants reported taking the drug daily over the past 3 days

HIV Infection TDF2 OLE, Botswana,  No HIV infections were observed among participants after initiation of TDF/FTC  5-6 cases of HIV infections would have been expected based on the TDF2 RCT incidence rate

CONCLUSIONS

Conclusions  High adherence to daily PrEP among both heterosexual men and women at risk for HIV  Supports recent findings that women and men who are at risk for HIV can adhere to daily PrEP  Slight decrease in the number of sex partners and condomless sex acts during the course of the study  PrEP is a highly effective HIV prevention strategy when taken consistently

Limitations  TDF2 OLE study population participated in a previous clinical trial  Self-selected, motivated individuals joined TDF2 OLE  Not yet completed drug level testing for all study participants

Next Steps  Intracellular drug level testing using dried blood spot cards  Analysis of the TDF2 OLE qualitative substudy to understand barriers and facilitators of adherence and visit attendance  Investigate differences in adherence between men and women

Ke a Leboga!  TDF2 and OLE participants  Botswana MOH  Gilead Sciences, Inc.*  CDC  Taraz Samandari  Amy Martin  Chou-Pong Pau  Chuck Rose  Felicia Hardnett  Lisa Harper  Michael Thigpen  Lynn Paxton  TDF2 OLE 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 *Gilead Sciences, Inc. provided the open-label Truvada® during the conduct of this study. They had no involvement in the study conduct and data analysis.

Faith L. Henderson, MPH Allan W. Taylor, MD, MPH National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention Division of HIV/AIDS Prevention Author Contact Information The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.