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Pharmacology Supports on Demand Dosing in MSM/TW

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Presentation on theme: "Pharmacology Supports on Demand Dosing in MSM/TW"— Presentation transcript:

1 Pharmacology Supports on Demand Dosing in MSM/TW
David V. Glidden, Ph.D. Professor of Biostatistics University of California at San Francisco IAS 2016, Durban

2 Randomized Evidence: IPERGAY 86% Effectiveness in MSM1 Biological Efficacy Adherence/ Acceptability Animal Studies Pharmacology IPERGAY drug levels 82-86% detection in plasma2 Rectal Protection Macaques Identification of Protective Level8 ADAPT Study Coverage of Sex in 6/6 protected6 Onset of Protection9,10 Bangkok: 74% of MSM3 Protective as daily7 New York: 52% of MSM4 Cape Town: 52% of women5 1. Molina, 2015 3. Holtz, 2015 5. Bekker, 2015 8. Anderson, 2012 9. Seifert, 2015 2. Fonsart, 2014 4. Mannheimer, 2015 6,7 Garcia-Lerma, 2008, 2010 10. Cottrell, 2016

3 Pharmacology Evidence
Dosing Pattern Drug Levels Clinical Outcomes Defined Dosing TFV-DP HIV Incidence BMD Small Pharmacology Studies Clinical Studies with Pharmacology For on Demand Dosing Cell PrEP Study iPrEx Randomized Initiation of Daily Dosing TFV-DP in vPBMCs HIV

4 iPrEx Randomized Study
10 HIV+ at enrollment 1080 MSM Placebo TDF/FTC 1086 MSM 160 TG 163 MSM 1135 HIV- 83 HIV+ 1176 HIV- 48 HIV+ 144 HIV- controls 48 HIV+ cases TFV-DP in vPMBC detected in 52/144 control TFV/FTC plasma in detected in 63/144 TFV-DP in vPBMC detected in 3/42 TFV/FTC plasma detected in 4/44 Estimated EC90:16, 95%CI (3-28) fmol TFV-DP/ 106 vPBMC Grant et al. NEJM, 2010 Anderson et al. Sci. Trans. Med., 2012

5 Protective Concentration
Anderson et al., Sci. Trans. Med

6 iPrEx Open Label No infections ≥ 4 tablets/week
Grant et al, Lancet Inf. Dis. 2014

7 Cell PrEP: Design 21 HIV- TDF/FTC naive volunteers
10 Female 11 Male Median (Range) Age 31 (20- 47) Weight (kg) 81 (56-124) BMI kg/m2 27 (21- 38) eGFR ml/min/1.73m2 93 (68-129) Black White Hispanic Initiate Daily TDF/FTC Stop/ Washout End Day vPBMC sampled fresh lysed PMBCs, assayed for TFV-DP Seifert et al., Clin. Infect. Dis. 2015

8 Estimated Protection (95%CI)
Cell PrEP: Results Tablets % Reaching EC90 Estimated Protection (95%CI) 1 17% 77% (40% to 93%) 2 44% 89% (51% to 98%) 3 71% 96% (60% to 100%) 4 84% 98% (67% to 100%) 7 90% 99% (70% to 100%) Seifert et al., Clin. Infect. Dis. 2015

9 Future Directions Plausible protective levels in MSM/TW onset within 4 pills with isolated use Persistence of levels remains unclear not clear how long need to persist Need in vivo EC90 for women, MSW, IDU ≥ 98% protection in vagina after 3 days Cottrell et al., J. Inf. Dis., 2016

10 Jose Castillo-Mancilla
Megha Mehrotra Juan Guanira Carlos Mosquera Lorena Vargas Sybil Hosek Jaime Martinez Peter Anderson Sharon Seifert Lane Bushman Jose Castillo-Mancilla Grace Chow Ana Martinez

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