hivnet 015: the explore trial susan buchbinder, md director, hiv research section
DESCRIPTION
HIVNET 015: The Explore Trial Susan Buchbinder, MD Director, HIV Research Section San Francisco Dept. of Public Health. Prevalence of HIV in US MSM NHBS: MMWR 2005;54:597-601. HIV Prevalence in South American Cities S Montano, JAIDS 2005; 40:57-64. - PowerPoint PPT PresentationTRANSCRIPT
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HIVNET 015: The Explore Trial
Susan Buchbinder, MDDirector, HIV Research Section
San Francisco Dept. of Public Health
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Spread of HIV in sub-Saharan Africa, 1987
Spread of HIV in sub-Saharan Africa, 1987
Estimated percentage of adults
(15–49) infected with HIV
Estimated percentage of adults
(15–49) infected with HIV
16.0% – 32.0%
8.0% – 16.0%
2.0% – 8.0%
0.5% – 2.0%
0% – 0.5%
trend data
unav ailable
outside region
16.0% – 32.0%
8.0% – 16.0%
2.0% – 8.0%
0.5% – 2.0%
0% – 0.5%
trend data
unav ailable
outside regionWorld HealthOrganizationWorld HealthOrganization UNAIDS–Addis–May 1999UNAIDS–Addis–May 1999
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Spread of HIV in sub-Saharan Africa,1997
Spread of HIV in sub-Saharan Africa,1997
Estimated percentage ofadults(15–49) infected with HIV
Estimated percentage ofadults(15–49) infected with HIV
16.0% – 32.0% 8.0% – 16.0% 2.0% – 8.0% 0.5% – 2.0%
0% – 0.5%trend data
unavailableoutside region
16.0% – 32.0% 8.0% – 16.0% 2.0% – 8.0% 0.5% – 2.0%
0% – 0.5%trend data
unavailableoutside region
World HealthOrganizationWorld HealthOrganization UNAIDS–Ad dis–M ay 1999UNAIDS–Ad dis–M ay 1999
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Prevalence of HIV in US MSMNHBS: MMWR 2005;54:597-601
40
19 18 1824
0
5
10
15
20
25
30
35
40
HIV Prevalence (%)
Baltimore LA Miami NYC SF
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HIV Prevalence in South American CitiesS 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%
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Estimated number of adults and childrennewly infected with HIV during 2004
Total: 4.9 (4.3 – 6.4) million
Western & Central Europe21 00021 000
[14 000 – 38 000][14 000 – 38 000]
North Africa & Middle East92 00092 000
[34 000 – 350 000][34 000 – 350 000]
Sub-Saharan Africa3.1 million3.1 million
[2.7 – 3.8 million][2.7 – 3.8 million]
Eastern Europe & Central Asia210 000210 000[110 000 – 480 000][110 000 – 480 000]
East Asia290 000290 000
[84 000 – 830 000][84 000 – 830 000]South & South-East Asia
890 000890 000[480 000 – 2.0 million][480 000 – 2.0 million]
Oceania5 0005 000
[2 100 – 13 000][2 100 – 13 000]
North America44 00044 000
[16 000 – 120 000][16 000 – 120 000]
Caribbean53 00053 000
[27 000 – 140 000][27 000 – 140 000]
Latin America240 000240 000
[170 000 – 430 000][170 000 – 430 000]
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Estimated US Cases HIV/AIDS by year of diagnosis
33 areas with name-based HIV infection reporting
0
2000
4000
6000
8000
10000
12000
14000
16000
2000 2001 2002 2003
MSM
Hetero
IDU
MSM+IDU
MMWR 2004;53:1106-10MMWR 2004;53:1106-10
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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
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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
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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
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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
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Measurements
• HIV antibody q 6 months
• Interviewer administered Demographics STD history
• ACASI (audio computer-assisted self interview) Sexual risk Drug use
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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
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Enrollment by site
Site N
Boston 729
Chicago 624
Denver 726
New York 737
San Francisco 736
Seattle 743
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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
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Baseline Demographics Intervention Standard N % N % p-value Age (years) 16-19 43 2 50 2 0.97 20-25 359 17 362 17 26-30 450 21 463 22 31-35 458 21 452 21 36-40 376 18 379 18 >40 458 21 445 21 Race/ethnicity White 1559 73 1553 72 0.77 Latino 322 15 330 15 Black 131 6 150 7 Asian/Pacific Isl. 63 3 53 2 Native American 17 1 14 1 Other/unknown 52 2 51 2
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Baseline Partners
In last 6 months: Intervention StandardN % N % p-value
No. male partners 0 25 1 17 1 0.26 1 142 7 164 8 2-5 678 32 704 33 6-9 393 18 357 17 >10 904 42 908 42
Female sex partner 86 4 92 4 0.66
HIV+ male partner 595 28 620 29 0.43
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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
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Adherence to initial sessions
No. of initial session-modules % completing
0 1
1-3 12
4-6 5
7-9 7
10+ 75
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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
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RetentionGroup 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+ 92.2P<0.05 for all comparisons
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HIV SeroincidenceOverall seroincidence = 2.1 (1.9, 2.4) per 100 py
Pe
rce
nt f
ree
of H
IV
0.9
00
.92
0.9
40
.96
0.9
81
.00
Months 6 12 18 24 30 36 42 48
OR 0.67 0.61 0.83 1.17 0.73 1.32 0.75 1.05
.918
.931
OR 0.67 0.61 0.83 1.17 0.73 1.32 0.75 1.05
Intervention
Control
Efficacy: 18.2% (-4.7, 36.0)
Adj Efficacy: 15.7% (-8.4, 34.4)
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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?
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Sexual behavior outcomes: UA, SDUA & SDURA
Unadjusted AdjustedEfficacy Efficacy
In last 6 months: (95% CI) (95% CI)
Unprotected anal(UA)
13.9(5.6, 21.5)
13.2(4.8, 20.9)
Unprotected analwith +/unk. statuspartner (SDUA)
14.8(6.5, 22.4)
13.2(4.8, 20.9)
Unprotectedreceptive anal with+/unk. status partner(SDURA)
20.5(10.9, 29.0)
22.5(13.3, 30.7)
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Surrogate True ClinicalEndpoint OutcomeDisease
True ClinicalOutcome
SurrogateEndpoint
Disease
Time
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Surrogate HIV Endpoint Infection
Intervention
Risk
HIVInfection
SurrogateEndpoint
Risk
Intervention
Time
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Self reported HIV6 mo. UA effects Infection
Intervention
Risk
• Potential Differences between self reported risk behaviors and true risk behaviors
• Alternative Pathways for risk of HIV infection
• Durability of effect
Time
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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?
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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)
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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