Post on 06-Jan-2018
description
1IAS 2010 20July
The Caprisa 004 result in context
Sheena McCormackClinical Scientist
MRC Clinical Trials Unit
2IAS 2010 20July
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
3IAS 2010 20July
40 trials of 33 interventionsType of intervention
BeneficialEffect
AdverseEffect
NoEffect
Total
Behaviour & microfinance
8 8
STI intervention 1 8 9Circumcision 3 1 4Diaphragm 1 1Non-ARV microbicides
1 11 12
ARV microbicides 1 1ARV oral 1 1Vaccines 1 3 4
Adapted from Padian et al AIDS 2010, 24:621
4IAS 2010 20July
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?
5IAS 2010 20July
Size of effect and strength of evidence
60
51
71
72
77
58
39
31
51
53
61
42
6
1
19
22
34
21
0 20 40 60 80 100
Mwanza STI intervention
3 circumcision trials
RV144 vaccine trialCaprisa 004
In context of results to date
6IAS 2010 20July
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
7IAS 2010 20July
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
8IAS 2010 20July
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
9IAS 2010 20July
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
10IAS 2010 20July
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
11IAS 2010 20July
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
12IAS 2010 20July
the Caprisa 004 participants
their partnersthe dedicated
study teamthe communities that supported
the trialthe donors, reviewing authorities
Thank you to…