Transcript EXPLORE Study - UCSF Center for AIDS Prevention Studies …

HIVNET 015: The Explore Trial
Susan Buchbinder, MD
Director, HIV Research Section
San Francisco Dept. of Public Health
Spread of HIV in sub-Saharan Africa,
1987
Estimated
Estimated percentage
percentage of
of adults
adults
(15–49)
(15–49) infected
infectedw
with
ith HIV
HIV
16.0%
16.0% –– 32.0%
32.0%
8.0%
8.0% –– 16.0%
16.0%
2.0%
2.0% –– 8.0%
8.0%
0.5%
0.5% –– 2.0%
2.0%
0%
0% –– 0.5%
0.5%
trend
trend data
data
unav
unav ailable
ailable
World
WorldHealth
Health
Organization
Organization
outside
outside region
region
UNAIDS–Addis–May
UNAIDS–Addis–May 1999
1999
Prevalence of HIV in US MSM
NHBS: MMWR 2005;54:597-601
40
35
30
25
20
15
10
5
0
40
24
19
18
18
HIV Prevalence (%)
Baltimore
LA
Miami
NYC
SF
HIV Prevalence in South American Cities
S Montano, JAIDS 2005; 40:57-64
Country
Number of MSM
HIV prevalence
Columbia
660
19.7%
Ecuador
490
14.5% - 27.8%
Peru
7041
13.7%
Bolivia
234
14.6% - 23.7%
Paraguay
92
13.0%
Uruguay
317
21.8%
Argentina
742
15.4%
Estimated number of adults and children
newly infected with HIV during 2004
44 000
Caribbean
[14 000 – 38 000]
[110 000 – 480 000]
210 000
North Africa & Middle East
53 000
[27 000 – 140 000]
Latin America
240 000
Eastern Europe
& Central Asia
21 000
North America
[16 000 – 120 000]
Western & Central
Europe
[170 000 – 430 000]
92 000
[34 000 – 350 000]
Sub-Saharan Africa
3.1 million
[2.7 – 3.8 million]
East Asia
290 000
[84 000 – 830 000]
South
& South-East Asia
890 000
[480 000 – 2.0 million]
Oceania
5 000
[2 100 – 13 000]
Total: 4.9 (4.3 – 6.4) million
Estimated US Cases HIV/AIDS by year of
diagnosis
33 areas with name-based HIV infection reporting
16000
14000
12000
MSM
Hetero
IDU
MSM+IDU
10000
8000
6000
4000
2000
0
2000
MMWR 2004;53:1106-10
2001
2002
2003
Background
• HIV epidemic throughout Americas (except parts of
Caribbean) most concentrated in MSM
 HIV prevalence 10-30%; HIV seroincidence 2-4%
despite ongoing risk reduction counseling
• Biomedical interventions (vaccines, PREP, STD rx,
microbicides) being developed, but still years away
• Behavioral interventions needed both as stand-alone
and to complement biomedical interventions
EXPLORE
• First behavioral intervention powered to address
impact of intensive intervention on HIV seroincidence
• “Cadillac version” of behavioral intervention intended
to maximize effects, likelihood for success
• Use of ACASI to get most accurate measures of risk,
correlate change in risk with change in seroincidence
Study Design
• Multi-site “RCT” (randomized controlled trial) efficacy
•
•
•
trial
Eligibility: (range of risk behaviors)
 Male, > 16 yo
 Any anal sex with man in last year
 Not in mutually monogamous relationship > 2 yrs
Intervention
 10 individualized sessions w/ boosters q 3 mos
Control
 Project Respect risk reduction counseling q 6 mos
Intervention modules
Modules
Content
1-3
Introductory and individual risk assessment, provide
basic risk reduction skills
4-5
Sexual communication (serostatus, facilitators/barriers)
6
Sex, drinking and drugs
7-9
Triggers for risk (places/events, partners, emotions)
10
Maintenance plan
Measurements
• HIV antibody q 6 months
• Interviewer administered
 Demographics
 STD history
• ACASI (audio computer-assisted self interview)
 Sexual risk
 Drug use
Outcomes
• Primary endpoint: HIV infection rates
• “Phase IIB” or screening efficacy trial
 If efficacy < 10%, discard or reformulate
 If 10-35%, plausibly efficacious, more study
 If > 35%, efficacious & implement
• Because Phase IIB are smaller than full efficacy trial,
less precision in measure
Enrollment by site
Site
N
Boston
729
Chicago
624
Denver
726
New York
737
San Francisco
736
Seattle
743
Recruitment Sources
Source
%
Clubs, bars, public venues
23
Advertisements
15
Mailings
14
Friend/acquaintances
13
Street outreach
11
Clinics, MDs
10
Other studies, CBOs, forums
14
Baseline Demographics
Intervention
N
%
Age (years)
16-19
20-25
26-30
31-35
36-40
>40
Race/ethnicity
White
Latino
Black
Asian/Pacific Isl.
Native American
Other/unknown
Standard
N
%
p-value
43
359
450
458
376
458
2
17
21
21
18
21
50
362
463
452
379
445
2
17
22
21
18
21
0.97
1559
322
131
63
17
52
73
15
6
3
1
2
1553
330
150
53
14
51
72
15
7
2
1
2
0.77
Baseline Partners
In last 6 months:
No. male partners
0
1
2-5
6-9
>10
Intervention
N
%
Standard
N
%
p-value
25
142
678
393
904
1
7
32
18
42
17
164
704
357
908
1
8
33
17
42
0.26
Female sex partner
86
4
92
4
0.66
HIV+ male partner
595
28
620
29
0.43
Baseline Sexual Practices
In last 6 months
Intervention
(%)
Standard
(%)
P value
Unprotected receptive anal
48
49
.47
Unprotected insertive anal
53
57
.04
Unprotected anal with HIV
positive or unknown partner
47
49
.16
Unprotected receptive anal
with HIV+/unknown partner
28
29
.74
Adherence to initial sessions
No. of initial session-modules
% completing
0
1
1-3
12
4-6
5
7-9
7
10+
75
Retention
Months
Intervention (%)
Standard (%)
P value
6
93.0
95.5
.0003
12
93.0
95.5
.0003
18
91.4
94.1
.0005
24
89.9
93.2
.0001
30
88.9
91.9
.0003
36
87.3
90.4
.0054
42
86.0
89.9
.0065
48
85.8
91.8
.0062
Retention
Group
Final visit retention (%)
Race/ethnicity
White
89.5
Af-Am/Latino/API/NAm/oth 83.9
Age (years)
< 25
80.0
26+
89.8
Female partners
No
88.5
Yes
74.2
Unprotected anal
No
89.0
Yes
86.7
Intervention sessions completed
<9
63.6
9+
92.2
P<0.05 for all comparisons
HIV Seroincidence
0.98
0.96
Intervention
0.94
Control
0.92
Efficacy:
18.2% (-4.7, 36.0)
.931
Adj Efficacy: 15.7% (-8.4, 34.4)
.918
0.90
Percent free of HIV
1.00
Overall seroincidence = 2.1 (1.9, 2.4) per 100 py
Months
OR
OR
6
12
18
24
30
36
42
48
0.67 0.61 0.83 1.17 0.73 1.32 0.75 1.05
0.67
0.61
0.83
1.17
0.73
1.32
0.75
1.05
Pre-set cutpoints for efficacy
• Efficacy 18.2% (95% CI: -4.7 to 36%)
• Adjusted efficacy 15.7% (95% CI: -8.4 to 34.4%)
• If lower bound 95% CI > 10%: declare efficacious
 Didn’t meet this cutpoint
• If upper bound 95% CI < 35%: no substantial efficacy
 Meet cutpoint to say no efficacy?
Sexual behavior outcomes:
UA, SDUA & SDURA
In last 6 months:
Unadjusted
Efficacy
(95% CI)
Adjusted
Efficacy
(95% CI)
Unprotected anal
(UA)
13.9
(5.6, 21.5)
13.2
(4.8, 20.9)
Unprotected anal
with +/unk. status
partner (SDUA)
14.8
(6.5, 22.4)
13.2
(4.8, 20.9)
20.5
(10.9, 29.0)
22.5
(13.3, 30.7)
Unprotected
receptive anal with
+/unk. status partner
(SDURA)
Time
Disease
Disease
Surrogate
Endpoint
True Clinical
Outcome
True Clinical
Outcome
Surrogate
Endpoint
Time
Intervention
Risk
Surrogate
Endpoint
HIV
Infection
Intervention
Risk
HIV
Infection
Surrogate
Endpoint
Time
Intervention
Risk
Self reported
6 mo. UA effects
HIV
Infection
• Potential Differences between
self reported risk behaviors and true risk behaviors
• Alternative Pathways for risk of HIV infection
• Durability of effect
Conclusions
• First study of impact of behavioral intervention for MSM on HIV
seroincidence
• Recruitment of large cohort, excellent retention
• Modest reduction in HIV seroincidence
 Can rule out substantial efficacy
 At cusp between discarding and pursuing further
• Significant reduction in self-reported risk behaviors
 Implications for using self-reported risk as endpoint in
intervention trials?
Future directions
• Rationale for further analysis and modification
 Significant reduction in risk
 Possibility of early effects
 Likelihood that control condition exceeds usual care
• Precautions
 Problems retaining young, diverse, risky MSM
 Unwieldy intervention
• Plans for exploratory analyses
 Subgroup analyses
 Focus groups w/ men of color
 Many other analyses (HSV2, HHV8, risk factors for infection)
Explore Study Team
• Co-chairs:
 Margaret Chesney
 Thomas Coates
 Beryl Koblin
• Site Principal Investigators
 Susan Buchbinder/Grant





Colfax
Connie Celum
Frank Judson
Beryl Koblin
Ken Mayer
David McKirnan