Transcript No Slide Title

Completed Observation of the Randomized
Placebo-Controlled Phase of iPrEx
Sponsored by
NIH/NIAID/DAIDS
with co-funding by the
Bill & Melinda Gates Foundation
and drug donated by
Gilead Sciences
Grant et al, IAS Rome 2011
The iPrEx Study
•
•
•
•
•
MSM and Trans women
Randomized 1:1 daily oral PrEP
FTC/TDF vs placebo
Prevention services provided to all
Followed monthly 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
New England Journal of Medicine, online Nov 23, 2010
iPrEx Timeline
Intention to Treat – Primary Analysis (May 1, 2010)
Intention to Treat – Final Analysis (Aug 2010)
Post Stop - Analysis (Nov 21, 2010)
Final DEXA/HBV Visit (February 28, 2011)
28 Feb 11
31 Dec 10
30 Sept 10
30 Jun 10
31 Mar 10
31 Dec 09
30 Sept 09
30 Jun 09
31 Mar 09
31 Dec 08
30 Sept 08
30 Jun 08
31 Mar 08
31 Dec 07
30 Sept 07
30 Jun 07
Enrollment
Grant et al, IAS Rome 2011
Fully enrolled as of December 2009
Sites
Participants
11
2499
San Francisco
Boston
Chiang Mai
Iquitos
Guayaquil
Lima
Sao Paulo
Rio de Janeiro
Cape Town
New England Journal of Medicine, online Nov 23, 2010
Efficacy (MITT) 42% (18-60%) Through End of Study
Infection Numbers: 83 – 48 = 35 averted
P = 0.002
Grant et al, CROI Boston 2011
Efficacy of Oral FTC/TDF PrEP
Subgroups
Efficacy
Age
Ethnicity
Region
Schooling
Alcohol (on days drank)
Circumcision
Trans Identity or
Feminizing Hormones
Unprotected Receptive
Anal Intercourse
P Value
<25 years
≥25 years
28%
56%
Hispanic
Non-Hispanic
40%
52%
Andes
Non-Andes
41%
49%
<Secondary
≥Secondary
14%
52%
<5 drinks
≥5 drinks
48%
43%
No
Yes
36%
83%
No
Yes
49%
-3%
No URAI
URAI
-25%
52%
p=0.18
p=0.63
p=0.75
p=0.16
p=0.81
p=0.10
p=0.14
p=0.03
Grant et al, IAS Rome 2011
Oral FTC/TDF Prophylactic Activity
N
TNF-DP (cells)
Cases
HIV+
48
9%
Controls*
HIV144
36%
TFV (plasma)
8%
40%
FTC-TP (cells)
11%
41%
FTC (plasma)
8%
40%
Any Drug
10%
44%
* Matched on site and time on study.
- 92% reduction in HIV risk associated with drug detection
at the timepoint nearest first evidence of infection.
-Analysis adjusted for age, URAI baseline and follow-up,
schooling, BMI.
Anderson et al, IAS, Rome 2011
Drug Detection in Hair
• Correlates to dose (DOT)
Drug detection, by region
• Opt-in substudy
o Not case matched
o 100 hairs cut
o FTC and TNF
• Higher detection in…
o Older persons
o US/SA
• Lower detection in…
o Trans-identified
Proportion with drug
detection
Liu CROI 2011
100%
90%
80%
55%
60%
40%
20%
0%
US/South Africa
South
American/Thai
N=94
N=128
Liu et al, IAS, Rome 2011
Unprotected Receptive Anal Intercourse
p=0.30
Perceived Drug Assignment
Based on Week 12 CASI
Randomized to
Believe they
are on...
FTC/TDF
Placebo
Placebo
115 (9%)
108 (9%)
Don’t Know
791 (63%)
784 (63%)
Truvada
275 (22%)
278 (22%)
No CASI
67 (5%)
81 (7%)
p=0.89
New England Journal of Medicine, online Nov 23, 2010
Unprotected Receptive Anal Intercourse
Those who believed they were taking FTC/TDF
p=0.44
Acute HIV Infection
Enrollment
Follow-up:
Placebo
Follow-up:
FTC/TDF
Visits
AntibodyHIV RNA+
2,499
10
11,322
11,407
p=0.004 for Placebo
p=0.002 for FTC/TDF
12
7
Percent of Fold Change
Visits
(95% CI)
0.4%
Ref
0.1%
-3.8
(-1.5 to -9.5)
0.06%
-6.5
(-2.2 to -20.2)
The Aims:
Provide post-trial access in accordance with the
Declaration of Helsinki and Good Participatory Practices.
Learn from PrEP users about implementation issues.
Learn if PrEP use increases when people know the tablet
is safe and effective and not a placebo.
Learn what happens with sexual practices.
Learn if every 12 week monitoring Is sufficient.
Status on
July 20, 2011
Site
San Francisco
Boston
Cape Town
Chicago
Brazil x 3
Chiang Mai
Ecuador
Peru
Status
Enrolling
Enrolling
Enrolling
Expected Aug ’11
Expected Aug ’11
Expected Aug ’11
Expected Aug ’11
Under IRB Review
Conclusions
Oral FTC/TDF PrEP provides additional protection against
the acquisition of HIV infection among MSM receiving a
comprehensive package of prevention services.
Detectable drug is associated with a
92% reduction in HIV risk after adjusting for other benefits.
Oral FTC/TDF use was nearly 90 to 100% at some sites;
Lower at other sites; Hair is promising for monitoring.
There is no evidence for risk compensation even among
those who thought they were taking FTC/TDF.
iPrEx ABSTRACTS AT IAS, Rome 2011
#
ABSTRACT #
PRIMARY
AUTHOR
1
MOLBPE035
RM. Grant
2
MOLBPE043
M. Merhotra
3
MOLBPE037
A. Liu
4
MOLBPE039
5
MOPE393
6
MOLBPE034
7
TULBPE024
8
TUPE363
9
WELBC04
10
CDC214
11
CDB467
ABSTRACT TITLE
FORMAT
PRESENTATION
DATE
Acute Pre-seroconversion HIV Infection at Baseline Prior to Starting Oral or Topical
Poster
Pre-Exposure Prophylaxis: iPrEx and CAPRISA 004
July 17th
Poster
July 17th
Poster
July 18th
P. Goicochea Social Adverse Events Experienced by Trans Women and Other Men who Have Sex Poster
with Men (MSM) Participating in a HIV Pre-Exposure Prophylaxis (PrEP) Trial
July 18th
P. Goicochea Strategizing Communications for Successful Dissemination of Study Results in HIV
Prevention Trials: The case of the iPrEx Study
July 18th
P. Anderson Expanded case-control analysis of drug detection in the global iPrEx trial
Poster
Depression among men who have sex with men (MSM) at risk for HIV infection in
A. Liu
Poster
the Global iPrEx Study
Adherence/Drug Detection Rates and Study Participant Experiences of Counseling
H. Gilmore Support among MSM in the iPrEx pre-exposure prophylaxis (PrEP) trial in San
Poster
Francisco, United States
July 18th
Local Risk Indicators Key for Targeting PrEP
Hair as a biological marker of daily oral pre-exposure prophylaxis (PrEP)
adherence and tenofovir/emtricitabine (TFV/FTC) exposure in the Global iPrEx
Study
Completed observation of the randomized placebo-controlled phase of iPrEx: daily
RM. Grant oral FTC/TDF pre-exposure HIV prophylaxis among men and trans women who
Oral
have sex with men
Forgotten Risk, Remembered Sex: Standard HIV Risk Questions Underestimate Sex
J. McConnell
E-poster
in Networks
Low Bone Mineral Density in Peruvian Young Men at High Risk for HIV Infection:
P. Gonzales
E-poster
Risk Factors
July 19th
July 19th
July 20th
17