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The Caprisa 004 result in context Sheena McCormack Clinical Scientist MRC Clinical Trials Unit

The Caprisa 004 result in context Sheena McCormack Clinical Scientist MRC Clinical Trials Unit. Outline. The RCTs that did and didn’t demonstrate significant reduction in HIV incidence Strength of evidence in context of results to date The pipeline for PrEP and microbicide effectiveness

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The Caprisa 004 result in context Sheena McCormack Clinical Scientist MRC Clinical Trials Unit

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  1. The Caprisa 004 result in context Sheena McCormack Clinical Scientist MRC Clinical Trials Unit 1

  2. Outline • The RCTs that did and didn’t demonstrate significant reduction in HIV incidence • Strength of evidence in context of results to date • The pipeline for PrEP and microbicide effectiveness • What’s missing 2

  3. 40 trials of 33 interventions Adapted from Padian et al AIDS 2010, 24:621 3

  4. In context of results to date • It is exciting • Proof of concept for ARV prophylaxis • Proof of concept for microbicides • Is it sufficient evidence to roll out globally? 4

  5. In context of results to date Size of effect and strength of evidence Mwanza STI intervention 3 circumcision trials RV144 vaccine trial Caprisa 004 5

  6. Caprisa strengths and limitations • Strengths: • Greater protection (54%) in more adherent users • Protection against HSV2 (51%) • Consistency across analyses • Consistent with ARVs preventing MTCT • Caprisa and non-Caprisa PK/PD supportive • Intermittent macaque challenge (with PK) supportive Parikh et al J Virol Oct 2009:10358 • Limitations: • Lower bound of 6% / p=0.017 • Single trial population 6

  7. Effectiveness in the pipeline • 2010-11 • iPrEx: oral, TDF/FTC, daily, MSM, Global • CDC4370: oral, TDF, daily, IDU, Thailand • 2012-13 • Ptnrs PrEP: oral, TDF & TDF/FTC, daily, couples, Kenya and Uganda • FEMPrEP: oral, TDF/FTC, daily, women, 5 countries in sub-Saharan Africa including SA • VOICE: oral & vaginal, TDF & TDF/FTC (oral combination only), daily, women, US and 4 countries in sub-Saharan Africa including SA 7

  8. What’s missing from RCTs? • Effectiveness (or otherwise) of intermittent vaginal dosing in more diverse populations, and with a single dose - before OR after • How long the intervals can be between testing without unacceptable risk of resistance • Rectal safety and effectiveness 8

  9. What else is missing? • Long term (>3yrs) genital safety, safety in pregnancy, adolescents, those have frequent sex • Better understanding of PK/PD in sexually active couples • Safest way to promote correct and consistent use 9

  10. Concluding remarks (1) • Excited – yes! Ready to roll out – no! • Proof of concept on two counts • ARV as prophylaxis • Microbicides as route of delivery (we already know that women and their partners like them) • The window for placebo controlled trials is open, but could be closing, and prioritising the questions is URGENT 10

  11. Concluding remarks (2) • Can’t ignore the challenge of delivering effective treatment to those that need it in resource limited settings • Managing the risk of resistance whether from non-adherence to treatment, or PrEP ‘monotherapy’ will determine the shape of the epidemic • Consultation, especially with communities, ethics committees and governments will be critical to success 11

  12. Thank you to… the Caprisa 004 participants their partners the dedicated study team the communities that supported the trial the donors, reviewing authorities 12

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