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HIVNET 015 A Randomized Clinical Trial of a Behavioral Intervention to Prevent Acquisition of HIV

HIVNET 015 A Randomized Clinical Trial of a Behavioral Intervention to Prevent Acquisition of HIV Among Men Who Have Sex With Men EXPLORE. Today’s presentation. Trial design Study conduct Baseline characteristics Counseling adherence & delivery Retention

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HIVNET 015 A Randomized Clinical Trial of a Behavioral Intervention to Prevent Acquisition of HIV

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  1. HIVNET 015 A Randomized Clinical Trial of a Behavioral Intervention to Prevent Acquisition of HIV Among Men Who Have Sex With Men EXPLORE

  2. Today’s presentation • Trial design • Study conduct • Baseline characteristics • Counseling adherence & delivery • Retention • Results on HIV seroincidence (the primary endpoint) • Results on sexual behavior outcomes (secondary endpoints)

  3. EXPLORE Trial Design • Multi-site, phase IIb two-armed, randomized controlled trial • Eligibility: • male • 16+ yrs. of age • HIV-negative • anal sex with male in last year • not in mutually monogamous relationship with HIV- for 2+ yrs • Intervention and control conditions • Intensive risk reduction vs. semiannual CDC Project RESPECT model of voluntary counseling and testing • 1:1 randomization

  4. EXPLORE Trial Design • Follow-up assessments • HIV testing and risk assessment every six months • Common closeout date: July 31, 2003 • Average follow-up time: 3.25 years (2.5 to 4 years) • Data: • interview: demographics, reasons for participating, STD history, use of PEP, counseling history • ACASI: sexual behaviors, alcohol/drug use, psychosocial variables • Blood specimen: HIV-1 and HSV-2 antibodies • Urine and rectal swabs: gonorrhea

  5. EXPLORE Behavioral Intervention • 10 counseling modules given within 4-6 months of randomization • Followed by quarterly maintenance sessions • Individualized to participant’s pattern of risk • Sessions 1-3: Introductory & individual risk • Provide basic risk reduction skills • Explore recent risk episodes: Crossing acceptable risk limits • Alcohol, substance use, environments, self-efficacy, communication skills, norms, partner types

  6. EXPLORE Behavioral Intervention • Sessions 4-5: Sexual communication • Serostatus, facilitators/barriers to communication • Session 6: Sex, drinking and drugs • Sessions 7-9: Triggers • Places/events, partners, emotions • Session 10: Maintenance Plan • Quarterly Follow-up Visits

  7. Monitoring adherence • Intervention session completion • Quality assurance scores • All sessions audiotaped • scores based on 10% random sample of tapes • scores above 80% --> acceptable • Duration of sessions • intervention > standard

  8. Community involvement • Site CABs involved in EXPLORE pilot study • National CAB coined study name • Sites utilized CAB expertise in designing recruitment and retention strategies • Some sites partnered with local CBOs to increase diversity of participants and staff

  9. Explore Phase IIb trial guidelines • Phase IIb design: • high efficacy: high probability to establish benefit • totally ineffective: high probability to rule out benefit • lower but important level of efficacy: high probability to establish benefit or indicate plausible efficacy

  10. Explore Phase IIb trial guidelinesfor HIV endpoint • Reduction in HIV incidence >= 10% (lower bound of CI >= 10%)  intervention beneficial • If not, and reduction < 35% (upper bound of CI < 35%)  benefit ruled out • Otherwise  intervention plausibly efficacious with merit for further evaluation

  11. Explore Phase IIb trial guidelinesfor HIV endpoint 35 10 0 Beneficial Rule out benefit Plausibly efficacious

  12. EXPLORE Timeline Recruitment Jan 99 Feb 00 Feb 01 Feb02 Feb 03 July 03

  13. EXPLORE Study Conduct

  14. Screenings and enrollments 4,862 screening visits - Not eligible at screen 53 - HIV(+) by test 93 - Eligible, not enrolled 420 - Randomized, excluded 1 - Randomized, analyzed 4,295 intervention 2,144 standard 2,151

  15. Enrollment by site Site N Boston 729 Chicago 624 Denver 726 New York 737 San Francisco 736 Seattle 743 TOTAL 4295

  16. Recruitment source Source % Clubs, bars,public venues 23 Ads 15 Mailings 14 Friend 13 Street outreach 11 Clinics, MDs 10 Other studies, CBOs, forums 14

  17. Baseline Characteristics

  18. Baseline Characteristics

  19. Baseline Characteristics

  20. Baseline Characteristics

  21. Counseling Adherence & Delivery: Initial session completion No. of initial session-modules % completing 0 1 1-3 12 4-6 5 7-9 7 10+ 75

  22. Counseling Adherence & Delivery: Maintenance session completion Month of % receiving maintenance visit counseling 9 73 15 73 21 72 27 73 33 65 39 61 45 48

  23. Counseling Adherence and Delivery:QA scores and Duration • QA score >= 80% • Initial intervention sessions: 83.3% • Intervention follow-up sessions: 77.0% • Standard arm sessions: 79.1% • Average session duration (minutes): • Intervention follow-up: 38 • Standard: 22

  24. Visit-retention Study-retention Intervention Standard P-val Intervention Standard P-val Mon N % N % % % 6 2144 86.4 2151 92.6 <.0001 93.0 95.5 0.0003 12 2144 85.3 2151 89.9 <.0001 93.0 95.5 0.0003 18 2144 84.2 2151 89.0 <.0001 91.4 94.1 0.0005 24 2144 83.7 2151 88.8 <.0001 89.9 93.2 0.0001 30 2144 84.1 2151 88.3 <.0001 88.7 91.9 0.0003 36 1588 83.8 1590 87.3 0.0045 87.3 90.4 0.0054 42 1061 83.5 1060 88.3 0.0015 86.0 89.9 0.0065 48 423 85.8 414 91.8 0.0062 85.8 91.8 0.0062 Retention

  25. Retention Group Final visit retention (%) Race/ethnicity White 89.5 Others 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

  26. Statistical analyses • Primary outcome: HIV infection • intent-to-treat analysis • Secondary analysis • behavioral outcomes: • unprotected anal (UA) • unprotected anal with +/unknown status partners (SDUA) • unprotected receptive anal with +/unknown status partners (SDURA)

  27. Intervention Standard 0.931 0.918 Standard arm at-risk 2081 2025 1960 1909 1862 1342 878 349 events 23 35 21 21 21 11 11 1 Intervention arm at-risk 2032 1974 1918 1865 1807 1299 848 331 events 15 21 17 24 15 14 8 1 OR 0.67 0.61 0.83 1.17 0.73 1.32 0.75 1.05 HIV SeroincidenceOverall seroincidence = 2.1 (1.9, 2.4) per 100 py 1.00 Intervention arm: 115 events / 6,037 py Standard arm: 144 events / 6,203 py 0.98 0.96 Percent free of HIV 0.94 OR: 0.818 (95% CI: 0.640, 1.047) efficacy: 18.2% (-4.7, 36.0) 0.92 Adjusted OR: 0.843 (95% CI: 0.656, 1.084) efficacy: 15.7% (-8.4, 34.4) 0.90 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

  28. Standard Intervention P-val Baseline Var Subgroup Size Events Size Events OR 95% CI NE Alcohol use None 221 13 228 10 0.75 0.33 1.72 0.502 Light 1026 62 978 47 0.82 0.56 1.20 0.310 Moderate 677 49 694 35 0.71 0.46 1.09 0.118 Heavy 219 20 234 21 0.97 0.53 1.81 0.933 Non-inj drug use No 764 31 749 17 0.57 0.31 1.03 0.062 Yes 1382 113 1392 98 0.88 0.67 1.15 0.348 Depression No 1143 67 1117 49 0.76 0.53 1.10 0.152 Yes 1006 77 1024 66 0.86 0.62 1.20 0.372 HIV Seroincidence: Subgroup Analyses Need to edit - can’t do!

  29. Sexual behavior outcomes: UA, SDUA & SDURA 1.0 Overall SDUA OR: 0.852 (95% CI: 0.775, 0.937) Overall UA OR: 0.861 (95% CI: 0.785, 0.944) 0.8 UA-S 0.6 UA-I Percent 0.4 SDUA-S SDUA-I 0.2 0.0 Months 6 12 18 24 30 36 42 48 SDUA:OR 0.75 0.81 0.85 0.94 0.92 0.80 0.89 1.28 NEED TO UPDATE with SDURA UA:OR 0.77 0.81 0.87 0.94 0.90 0.82 0.95 0.96

  30. plot

  31. Sexual behavior outcomes: UA, SDUA & SDURA

  32. Summary (1) • First study to test a behavioral intervention specifically for MSM against HIV endpoint • Trial conducted over an extended period of time • Successful recruitment of large high-risk MSM cohort • Intervention and standard conditions delivered with high fidelity to the protocol • Retention reached high standard for behavioral intervention • A-CASI technology to obtained self-report behaviors

  33. Summary (2) • 18% reduction in HIV acquisition • adjusted analysis for imbalances at baseline and differential retention: 16% • suggestion of more favorable effect in first 12 to 18 months • Reduction in unprotected anal sex • 14% reduction in UA • 15% reduction in SDUA • 21% reduction in SDURA

  34. Limitations • Cohort not representative of all MSM in cities • eligibility criteria • men of color, younger men and lower SES less likely to enroll and more likely to drop out • Full effect of intervention may have been muted • standard condition: Project RESPECT VCT • attention given for study retention • length of study

  35. Limitations • Retention differential • excess in lost-to-follow-up in intervention arm explained by those who did not complete the initial 10 intervention sessions • Standard arm: 92% • Intervention arm 9+ sessions: 92% • Intervention arm <9 sessions: 64%

  36. Conclusions • Results rule out 35% reduction in HIV infection rate relative to standard arm • Modest benefit plus more favorable estimates of effect in first 12 to 18 months plus significant effects on risk behavior suggest prevention of HIV infection by a behavioral intervention is feasible • Challenge is maintenance of behavior change over extended periods of time.

  37. Next? • Dissemination of initial results • Analyses of EXPLORE data • generate hypotheses to help develop more highly efficacious behavioral interventions

  38. National dissemination plan • Audiences • Study staff • work with site PI • Study participants • final newsletter • community forums • Community • CABs, CBOs, service providers, advisory committees, PPG, political bodies, other researchers, etc. • Media • centralized press release and Q&As

  39. 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 Explore Study Team (1)

  40. Fenway Community Health Center: Felipe Agredano, Rodrigo Barahona, Keith Bell, Christine Borges, Manual Burnias, Mark Cayabayab, Dan Church, Allison Cohn, Yvonne Colon, Janet Dargon,Nancy DeSousa, Judy Erdman, Josh Gagne, Eliza Goodhue, Juan Jimenez, William Johnson, Wilfred Labiosa, Ana Lara, Darren LeBlanc, Vin Longo, Marc Manseau, Marshall Miller, Matthew Mimiaga, Elie Mohns, Arnel Montenegro, David Pantalone, Oscar Patino, Tracey Rogers, Edual Ruiz, Liz Salomon, Julio Silva, Laura van der Leeden, Rodney VanDerwarker, Curt Weber. Howard Brown Community Health Center:Althea Batticks, Jason Bird, Liz Bradshaw, Robert Brown, Tom Buckingham, Toni Buckingham, Kelly Carson, Irene Chubinsky, Scott Clark, Scott Cook, Jeff Eichholz, Erica Gaffold,Sanford Gaylord, Mark Hartfield, David Henry, Brent Hope, Dale Gluth, Shane Gosselink, Jenny Hopwood, Laura Hosto, Jennifer Howard, D. J. Jacques, Heather Jandura, Susan Killelea, ndy Knight, Simone Koehlinger, Melissa Kohnke, Felicity LaBoy, Han Lee, Kandis Martin,Nicole Martin, Michele McGrady, Cheron McNeal, Denise Miles, Gino Moore, Michael Munn, Jose Narvaez, Aisha Nawab, Arlette Oblaza, Kevin O’Keefe, Liz Perez, Elisse Pertiller, Kelly Picketts, Borris Powell, Chris Powers, Bart Ramey, Ingrid Rodriguez, Laurez Rutledge, Porfirio Sanchez, Michael Saven, Chris Schmidt, Mark Schulze, Jim Skinner, David Snyder, Al Sorrese, Justin St. Andre, Gerry Taranzo, Ted Taylor, Sonia Torres, Kristin Vanfossan, Gregory Victorianne, Erik Wetz. Explore Study Team

  41. Denver Public Health:Misty Aas, Ramon Armendariz, Chloe Bailey, Brian Bost, Julie Caine David Cline, Stuart Cooper, Kent Curtis, Beth Deyo, John Douglas, Michael Furhman, Rene Gonzalez, Jeff Hiller, Paul Huber, Sharon Huber, Ken Miller, Philip Osteen, Laurie Peter, Doug Robinson, Dave Ward, Tim Wright, Andrew Yale. New York Blood Center:Anne Aldrich, Louise Austin, Lynne Bartell, Jane Bensel, Roberta Bernet, Damian Bird, Adam Bonilla, Carolyn Booher, Michael Camacho, Bradley Clark, Kent Curtis, Nikki Englert, Tonya Flores, George Gates, Corinne Geller, Octavio Gonzalez, Denise Goodman, Krista Goodman, Joshua Hinson, Sean Lawrence, Thomas Lee, Jay Loeffel, Angelo Luna, Larry Metzger, Carolle Morris, Patrick O’Quinn, Eric Ortiz, Ofiji Parris, Alfredo Perez, Terrence Precord, Alberto Rodriguez, Jason Santiago, Craig Siulinski, Leah Strock, Paul Teixeira, Eric Torres, Francesca Valenti, Curt Weber, Avery White, and Jess Zimmerman Explore Study Team…more

  42. University of Washington:Scott Britt, Fransing Daisy, Aline Dang, Tennessee Dickenson, Niles Eaton, Terry Elliott, Raymond Evans, Paul Farley, Mark Fleming, George Froehle, Jerome Galea, Hal Garcia Smith, Patrick Gonzalez, Bruce Gooding, Krista Goodman, Justin Haines, Rick Hieb, Keifa Herzog, Rick Hieb, Eric Hildebrandt, Damon Jameson, EJ Janson, Thom Kelty, Bill Krutch, Erin Lennon, Matt Leidholm, Alfredo Lopez, Paul Louey, Matt Meko, Jenny Melmed, Dany-Paul Mucha, Shelley Ozscuro, Joe Picciano, Jim Price, Monica Rayne, Alex Rodriguez, Barbara Steele, Nancy Stoaks, Jason Stucky, Matthew Swank, Stephen Tabet, Jeff Thompson, Dennis I. Torres, John Torres, Patrick Tschumper, Paul B. Verano, Ken Wheeler, Robert Yoon San Francisco Department of Public Health: Jonas Abella, Mike Ahern, Ari Bacharat, Alba Barreto, Christopher Boyden De Shazer, Jesse Brooks, Meredith Broome, Tony Buckman, David Colbert, Emily Cole, Grant Colfax, Alfonso Diaz, Michael Edgar, Beth Faraguna, Paige Fratesi, Vincent Fuqua, Reggie Gage, Anjali Garg, Dale Gluth, Ted Guggenheim, Gavin Hall, Thomas Knoble, Rachel Langdon, Irene Lee, Jennifer Lessard, Nicole Lightburn, Tim Matheson, Corvette Moore, Mario Moreno, Paul O’Malley, Jennifer Owen, Jesus Perez, Robin Rifkin, Chris Rubino, Mateo Rutherford, Jennifer Sarche, Georgia Schreiber, Rob Schwarz, Craig Siulinski, John Stryker, Jason Tomasian, Jim Touchstone, Seth Watkins, Sarah Wheeler, Belinda Van, and Allison Zerbe. Explore Study Team…more

  43. Center for AIDS Prevention Studies: Patrick Barresi, Kevin Filocamo, Cliff Leonardi, Scott Stumbo, Matthew Troy. Abt Associates Inc:Dana Benet, Sam Clark, Anne Coletti, Michelle Culp, Kirsten Firla, Michael Iatesta, Maria Madison, Sean McKee, George Seage. Statistical Center for HIV/AIDS Research and Prevention:Neil Albright, Geetha Beauchamp, Rana Bonnice, Lynette Browne, Claire Chapdu, Maya Covarrubias, Martina Deseyve, Lynda Emel, Alice Fisher, Eileen Hess, Sarah Holte, MaryAnn Klotz, Wolfe Maykut, Peter McDonnell, Barbara Metch, Geoff Minerbo, Lisa Ondrejcek, Jennifer Schille, Steve Self, Al Williams. Explore Study Team…and more

  44. MANY, MANY THANKS to the 4,295 EXPLORE men!

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