1 / 40

Timothy Mastro Family Health International XVII International AIDS Conference Mexico City 7 August 2008

Timothy Mastro Family Health International XVII International AIDS Conference Mexico City 7 August 2008. Rationale for ARV PrEP for HIV Prevention . Data suggesting that ARV PrEP may be effective ARVs for PMTCT Post-exposure prophylaxis for HIV Monkey models for SHIV transmission

pamelia
Download Presentation

Timothy Mastro Family Health International XVII International AIDS Conference Mexico City 7 August 2008

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Timothy Mastro Family Health International XVII International AIDS Conference Mexico City 7 August 2008

  2. Rationale for ARV PrEP for HIV Prevention • Data suggesting that ARV PrEP may be effective • ARVs for PMTCT • Post-exposure prophylaxis for HIV • Monkey models for SHIV transmission • Available ARVs appear safe • Available ARVs can be used once daily • TDF: tenofovir disoproxil fumarate: Viread ® • FTC: emtricitibine: Emtriva ® • TDF/FTC: Truvada ®

  3. Data from Monkey Studies at CDC:Prevention of Rectal SHIV Transmission by Chemoprophylaxis with ARVs Laboratory Branch, DHAP, CDC 100 FTC/Tenofovir (subcut, n = 6) 75 FTC/TDF (oral, n = 6) p = 0.0075, [HR = 7.8] % Uninfected animals 50 FTC (subcut, n = 6) p = 0.021, [HR = 3.9] 25 TDF (oral, n = 4)* p = 0.3 Control (n = 18) 0 0 2 4 6 8 10 12 14 Number of rectal exposures

  4. One Completed Clinical Trial • West Africa Phase II PrEP Trial (FHI/BMGF) • RCT: daily TDF 300mg and placebo • Women (n=936) in Ghana, Cameroon, Nigeria • Conducted June 2004 - March 2006 • No evidence of increased clinical or laboratory adverse effects • No evidence of risk compensation • Inadequate power to assess efficacy • 8 HIV seroconversions: 2 TDF, 6 placebo • RR = 0.35, p=0.24

  5. Ongoing PrEP Trials • Tenofovir Extended Safety Study (CDC) • Bangkok Tenofovir Study (CDC) • Botswana TDF2 (TDF/FTC) Trial (CDC) • iPrEX (UCSF/NIAID/BMGF) • Partners PrEP (UW/BMGF)

  6. Planned PrEP Trials • FEM-PrEP (FHI/USAID/BMGF) • VOICE (MTN 003) (NIAID)

  7. OnGOINGPrEP TRIALS

  8. U.S. Extended Tenofovir Safety Trial • Sponsor CDC • Objective To assess clinical, laboratory and behavioral safety; and adherence and acceptability • Design Randomized double-blind placebo controlled phase II extended safety study with 1:1 TDF : placebo • Duration 24 months with DSMB review of data every 6 months

  9. U.S. Extended Tenofovir Safety Trial • 400 HIV-neg MSM (Atlanta, San Francisco, Boston) • 9 month delay in enrollment of 200 men to assess behavioral changes once drug prophylaxis started • Close monitoring of seroconverters for resistance and clinical outcomes • Adverse events, and access to HIV care if infected, managed through physician referral • Started February 2005; fully enrolled July 2007; follow-up to end August 2009

  10. Bangkok Tenofovir Study (BTS)BMA Drug Treatment Clinics Sponsor: CDC TUC Lab (Nonthaburi) BMA Lab Thailand Bangkok

  11. Bangkok Tenofovir Study (BTS)

  12. BTS Objectives

  13. Botswana TDF-2 Study Sponsor: CDC

  14. Botswana TDF-2 Study • Trial started in 2005 with TDF; halted enrollment (at N=71) in March 2006 to prepare for switch to Truvada (TDF/FTC). • New trial (TDF-2) started in February 2007 • Study population originally 1200 heterosexual men and women aged 18-29 • Now planning to expand age range to 18-39 and increase N to 1800-2000 through addition of new site

  15. The iPrEx Study:Safety, Efficacy, Behavior, and Biology Sponsored by NIH/NIAID/DAIDS with co-funding by the Bill and Melinda Gates Foundation and drug donated by Gilead Sciences

  16. The iPrEX Study • Plans to enroll 3000 high-risk MSM • Randomized 1:1 daily oral PrEP • FTC/TDF vs Placebo • Followed on drug for: • HIV seroconversion • Adverse events (especially renal & liver) • Metabolic effects (Bone, Fat, Lipids) • HBV flares among HBsAg+ • Risk behavior & STIs • Adherence • If infected • Drug resistance • Viral load • Immune responses & CD4 count

  17. The iPrEX Study

  18. After 3 Years of Preparation, iPrEx is Enrolling as Planned

  19. Why MSM? • MSM bear a major burden of the epidemic • Throughout the Americas • In some parts of Asia • The burden in Africa is increasingly appreciated • Efficacy could be different after rectal exposure • Higher efficiency of transmission • Possibly different tissue penetration of virus and drug • iPrEx is the only efficacy trial of PrEP in MSM

  20. Partners PrEP • Multisite trial of pre-exposure prophylaxis against HIV in HIV discordant couples • Parallel comparison of TDF and TDF/FTC PrEP to prevent HIV-1 acquisition within HIV-1 discordant couples Jared Baeten, MD, PhD Connie Celum, MD, MPH University of Washington

  21. Where Partners PrEP Study Fits into the PrEP Research Landscape • When considering possible wide-spread implementation, HIV discordant couples would be a priority target • More than half of new HIV transmissions occur in stable couples • 3 Arm Trial: side-by-side evaluation of TDF and FTC/TDF • Will enroll and follow HIV+ partners • Assess PrEP efficacy vs. HIV+ partner characteristics (e.g., high viral load) • Drug levels to test for drug sharing (in context of counseling re: sharing) • Assess baseline and longitudinal resistance in HIV+ partners • marker / impact of sharing • transmitted vs. acquired resistance in seroconverters

  22. Partners PreP: Design

  23. Partners PrEP: Statistical Power • Sample size = 3900 HIV discordant couples • 1:1:1 randomization (common placebo arm) • estimated HIV incidence in placebo arm of 3.25%  With 191 endpoints, >80% power to detect 60% efficacy of each arm against placebo and ‘rule out’ <30% efficacy

  24. Partners PrEP: Timeline • Funding awarded from BMGF: mid-2007 • Protocol development and pre-IND: May 2007 • IND approved: September 2007 • Site preparedness, stakeholder sessions, IRB & national drug authority approvals: October 2007-present • First 2 sites activated: May & June 2008 • Additional 6 sites to be activated: Q3-Q4 2008 • Target enrollment period: 2 years • Completion of follow-up and results: 2011

  25. Planned PREP TRIALS

  26. FHI FEM-PrEP: Trial Overview

  27. FHI FEM-PrEP: Trial Objectives

  28. FEM PrEP: Timeline • Jun 2007 Initiation of non-research community activities (i.e., CABs) • Aug 2007 Initiation of site preparedness activities • Oct 2007 Investigators’ meeting (Nairobi) • Mar 2008 FHI PHSC approval • May 2008 IND submission • Jul 2008 1st training (Kenya) • Q4 2008 1st screening • Q3 2011 Trial completion (primary objective) • Q3 2012 Trial completion (seroconverter objectives)

  29. VOICE Vaginal and Oral Interventions to Control the Epidemic Sponsor: NIAID/NIH

  30. VOICE Study Objectives

  31. The VOICE Study • Safety and effectiveness study of tenofovir gel, tenofovir tablet and Truvada tablet for prevention of HIV infection in 4,200 women • Randomized trial with 5 study groups. Two sequential randomizations. Women will use product for average of 21 months

  32. VOICE Study Hypothesis • >25% difference in effectiveness • Between tenofovir 1% gel and placebo gel • Between TDF and oral placebo • Between FTC/TDF and oral placebo • No difference in safety • Between daily regimens of tenofovir 1% gel and placebo gel • Between daily regimens of TDF and oral placebo • Between daily regimens of FTC/TDF and oral placebo

  33. VOICE Study Sites South Africa Malawi Uganda Zambia Zimbabwe

  34. VOICE Study Timeline *Strategic Working Group, Division of AIDS, National Institute of Allergy and Infectious Diseases (NIAID) ** Prevention Sciences Review Committee, NIAID ***Division of AIDS, NIAID

  35. Summary of Ongoing PrEP Studies - I

  36. Summary of Ongoing PrEP Studies - II

  37. Summary of Planned PrEP Studies

  38. Total Participants in 7 Trials

  39. Next Steps • Intermittent vs. daily PrEP • New ARVs and combinations • Formulations: oral, injectable, gel, vaginal ring • Adolescents • Program implementation

  40. Acknowledgements • Lynn Paxton CDC • J Gerardo Garcia-Lerma CDC • Walid Heneine CDC • Bob Grant University of California, San Francisco • Connie Celum University of Washington • Lut Van Damme Family Health International • Amy Corneli Family Health International • Sharon Hillier Magee Hospital, University of Pittsburgh • Ward Cates Family Health International • Mitchell Warren AIDS Vaccine Advocacy Coalition

More Related