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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 - PowerPoint PPT Presentation
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Sponsored byNIH/NIAID/DAIDS
Completed Observation of the RandomizedPlacebo-Controlled Phase of iPrEx
with co-funding by theBill & Melinda Gates
Foundationand drug donated by
Gilead SciencesGrant et al, IAS Rome 2011
• 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
The iPrEx Study
New England Journal of Medicine, online Nov 23, 2010
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)
iPrEx Timeline
30 Ju
n 07
30 S
ept 0
7
31 D
ec 0
7
31 M
ar 0
8
30 Ju
n 08
30 S
ept 0
8
31 D
ec 0
8
31 M
ar 0
9
30 Ju
n 09
30 S
ept 0
9
31 D
ec 0
9
31 M
ar 1
0
30 Ju
n 10
30 S
ept 1
0
31 D
ec 1
0
28 Fe
b 11
Enrollment
Grant et al, IAS Rome 2011
Fully enrolled as of December 2009
Lima
IquitosGuayaquil
Sao Paulo
Rio de Janeiro
BostonSan Francisco
Cape Town
Chiang Mai
Sites 11Participants 2499
New England Journal of Medicine, online Nov 23, 2010
Efficacy (MITT) 42% (18-60%) Through End of StudyInfection Numbers: 83 – 48 = 35 averted
P = 0.002
Grant et al, CROI Boston 2011
Efficacy P Value
Age <25 years28%
≥25 years56% p=0.18
Ethnicity Hispanic40%
Non-Hispanic52% p=0.63
Region Andes41%
Non-Andes49% p=0.75
Schooling <Secondary14%
≥Secondary52% p=0.16
Alcohol (on days drank) <5 drinks48%
≥5 drinks43% p=0.81
Circumcision No36%
Yes83% p=0.10
Trans Identity or Feminizing Hormones
No49%
Yes-3% p=0.14
Unprotected Receptive Anal Intercourse
No URAI-25%
URAI52% p=0.03
Efficacy of Oral FTC/TDF PrEPSubgroups
Grant et al, IAS Rome 2011
Oral FTC/TDF Prophylactic ActivityCases
HIV+Controls*
HIV-N 48 144
TNF-DP (cells) 9% 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
90%
55%
0%
20%
40%
60%
80%
100%
US/South Africa South American/Thai
Prop
ortio
n w
ith d
rug
dete
ctio
n
Drug detection, by region
N=128N=94
• Correlates to dose (DOT)Liu CROI 2011
• Opt-in substudyo Not case matchedo 100 hairs cuto FTC and TNF
• Higher detection in…o Older personso US/SA
• Lower detection in…o Trans-identified
Liu et al, IAS, Rome 2011
Unprotected Receptive Anal Intercourse
p=0.30
Perceived Drug Assignment
Believe they are
on...
Randomized to
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%)
Based on Week 12 CASI
p=0.89New England Journal of Medicine, online Nov 23, 2010
Those who believed they were taking FTC/TDF
p=0.44
Unprotected Receptive Anal Intercourse
Acute HIV Infection
p=0.004 for Placebop=0.002 for FTC/TDF
Visits Antibody-HIV RNA+
Percent of Visits
Fold Change(95% CI)
Enrollment 2,499 10 0.4% Ref
Follow-up: Placebo 11,322 12 0.1%
-3.8 (-1.5 to -
9.5)Follow-up: FTC/TDF 11,407 7 0.06%
-6.5 (-2.2 to -
20.2)
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.
The Aims:
Status onJuly 20, 2011
Site StatusSan Francisco EnrollingBoston EnrollingCape Town EnrollingChicago Expected Aug ’11Brazil x 3 Expected Aug ’11Chiang Mai Expected Aug ’11Ecuador Expected Aug ’11Peru Under IRB Review
ConclusionsOral 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 a92% reduction in HIV risk after adjusting for other benefits.
There is no evidence for risk compensation even among those who thought they were taking FTC/TDF.
Oral FTC/TDF use was nearly 90 to 100% at some sites;Lower at other sites; Hair is promising for monitoring.
iPrEx ABSTRACTS AT IAS, Rome 2011# ABSTRACT # PRIMARY
AUTHOR ABSTRACT TITLE FORMATPRESENTATION
DATE
1 MOLBPE035 RM. Grant Acute Pre-seroconversion HIV Infection at Baseline Prior to Starting Oral or Topical Pre-Exposure Prophylaxis: iPrEx and CAPRISA 004
Poster July 17th
2 MOLBPE043 M. Merhotra Local Risk Indicators Key for Targeting PrEP Poster July 17th
3 MOLBPE037 A. LiuHair as a biological marker of daily oral pre-exposure prophylaxis (PrEP) adherence and tenofovir/emtricitabine (TFV/FTC) exposure in the Global iPrEx Study
Poster July 18th
4 MOLBPE039 P. Goicochea Social Adverse Events Experienced by Trans Women and Other Men who Have Sex with Men (MSM) Participating in a HIV Pre-Exposure Prophylaxis (PrEP) Trial
Poster July 18th
5 MOPE393 P. Goicochea Strategizing Communications for Successful Dissemination of Study Results in HIV Prevention Trials: The case of the iPrEx Study
July 18th
6 MOLBPE034 P. Anderson Expanded case-control analysis of drug detection in the global iPrEx trial Poster July 18th
7 TULBPE024 A. Liu Depression among men who have sex with men (MSM) at risk for HIV infection in the Global iPrEx Study
Poster July 19th
8 TUPE363 H. Gilmore Adherence/Drug Detection Rates and Study Participant Experiences of Counseling Support among MSM in the iPrEx pre-exposure prophylaxis (PrEP) trial in San Francisco, United States
Poster July 19th
9 WELBC04 RM. Grant Completed observation of the randomized placebo-controlled phase of iPrEx: daily oral FTC/TDF pre-exposure HIV prophylaxis among men and trans women who have sex with men
Oral July 20th
10 CDC214 J. McConnell Forgotten Risk, Remembered Sex: Standard HIV Risk Questions Underestimate Sex in Networks
E-poster
11 CDB467 P. Gonzales Low Bone Mineral Density in Peruvian Young Men at High Risk for HIV Infection: Risk Factors
E-poster
17