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