IAS 2010 20July 1 The Caprisa 004 result in context Sheena McCormack Clinical Scientist MRC Clinical...
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Transcript of IAS 2010 20July 1 The Caprisa 004 result in context Sheena McCormack Clinical Scientist MRC Clinical...
![Page 1: IAS 2010 20July 1 The Caprisa 004 result in context Sheena McCormack Clinical Scientist MRC Clinical Trials Unit.](https://reader035.fdocuments.us/reader035/viewer/2022062905/5a4d1ad07f8b9ab0599712b9/html5/thumbnails/1.jpg)
1IAS 2010 20July
The Caprisa 004 result in context
Sheena McCormackClinical Scientist
MRC Clinical Trials Unit
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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
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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
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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?
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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
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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
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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
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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
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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
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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
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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
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12IAS 2010 20July
the Caprisa 004 participants
their partnersthe dedicated
study teamthe communities that supported
the trialthe donors, reviewing authorities
Thank you to…