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C. Durier, C. Desaint, B. Silbermann, J.D. Lelièvre,

Impact à long terme de la participation aux essais vaccinaux VIH chez le volontaire sain Cohorte ANRS COHVAC. C. Durier, C. Desaint, B. Silbermann, J.D. Lelièvre,

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C. Durier, C. Desaint, B. Silbermann, J.D. Lelièvre,

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  1. Impact à long terme de la participation aux essais vaccinaux VIH chez le volontaire sainCohorte ANRS COHVAC C. Durier, C. Desaint, B. Silbermann, J.D. Lelièvre, L. Slama, P. Morineau-Le Houssine, L. Cuzin, I. Poizot-Martin, J.P. Aboulker, G Pialoux, B. Spire, O. Launay; pour la cohorte ANRS COHVAC

  2. VAC 20 VAC 18-II VAC 18-I VAC 16 VAC 17 VAC 14 VAC 12 VAC 10 LIP 03 VAC 09 VAC 08 VAC 07 VAC 06 VAC 05 VAC 04 VAC 03 VAC 02 VAC 01 ANRS Phase I/II Vaccine Trials 422 1992 1994 1996 1998 2000 2002 2004 2006 2008 2010 Recombinant envelope protein subunit (rgp160) ALVAC-HIV canarypox vectors expressing Env, Gag, Pro and CTL domains of Pol (vCP) Env V3 MN synthetic peptide (peptideV3) P24 / Env V3 MN synthetic peptide (CLTB-36) HIV-1 Lipopeptides representing CTL epitopes of Gag, Pol and Nef proteins * in a previous HIV vaccine trial Séminaires ANRS – 5/2011 COHVAC

  3. ANRS Volunteers Network • HIV-1 healthy, 21-54 years • Psychological and sociological stability • HIV-neg status by Elisa and WB • Pre-existing medical conditions, abnormal lab values  exclusion • Low risk of HIV infection • Counseling regarding the need to avoid HIV exposure • No financial incentive Séminaires ANRS – 5/2011 COHVAC

  4. TRIAL 1y+ ANRS Volunteers Network Trial completion Trial entry y1 y2 y3 y4 y5 y6 y7 y0 Retrospective collection Prospective follow-up ANRS COV1-COHVAC Prospective multicenter cohort study for long term follow-up of safety, serological evolution and evaluation of the consequences of participation in HIV preventive vaccine trials Séminaires ANRS – 5/2011 COHVAC

  5. ANRS COV1-COHVAC • Primary endpointSevere medical events (grade 3-4), neurological, ophthalmological, and immunological events • Secondary endpoints • Long-term HIV antibody response • Psychosocial and behavioral consequences of participation in HIV vaccine trials • Incidence of HIV infections Séminaires ANRS – 5/2011 COHVAC

  6. Methodology • Medical and biological follow-up HIV antibodies with 2 different licensed enzyme immunoassays (EIA) performed locally, and Western-Blot assay if positive • Vaccine-induced seropositivity (VISP) : 1 of EIA tests positive, regardless of Western-Blot results • Self-administered questionnaire • Socio-economic status • Social life • Concerns about trial participation • Sexual behavior approved by the National Committee on Informatics and Freedom (CNIL) Séminaires ANRS – 5/2011 COHVAC

  7. Presentations • Long-term vaccine inducedHIV seropositivity among HIV-uninfected healthy volunteers in ANRS COV1-COHVAC cohort 18th CROI 2011, Poster #372 • Psychosocial consequences of participation in HIV preventive vaccine trials: a cross-sectional study in ANRS COV1-COHVAC cohort Conference AIDS VACCINE 2010, Oral abstr. 03-01 AIDS Research and Human Retroviruses. October 2010, 26(10): A-1-A-184. Séminaires ANRS – 5/2011 COHVAC

  8. VAC 20 VAC 18-II VAC 18-I VAC 16 VAC 17 VAC 14 VAC 12 VAC 10 LIP 03 VAC 09 VAC 08 VAC 07 VAC 06 VAC 05 VAC 04 VAC 03 VAC 02 VAC 01 1992 1994 1996 1998 2000 2002 2004 2006 2008 2010 ANRS Phase I/II Trials 422 Recombinant envelope protein subunit (rgp160) ALVAC-HIV canarypox vectorsexpressing Env, Gag, Pro and CTL domains of Pol (vCP) Env V3 MN synthetic peptide (peptideV3) P24 / Env V3 MN synthetic peptide (CLTB-36) HIV-1 Lipopeptidesrepresenting CTL epitopes of Gag, Pol and Nef proteins All were injected IM except one mucosal and one ID trial Séminaires ANRS – 5/2011 COHVAC

  9. ANRS Trials Séminaires ANRS – 5/2011 COHVAC

  10. HIV antibodies at inclusion in COHVACCharacteristics of volunteersDec 2008- Sep 2010 Séminaires ANRS – 5/2011 COHVAC

  11. 100 80 60 % VISP (95% Confidence Interval) 40 20 0 Vaccine-induced seropositivity rate (VISP) by vaccine type Séminaires ANRS – 5/2011 COHVAC

  12. Time since injections by vaccine type 20 18 16 14 Years since injections (median, IQR, min-max) 12 10 8 6 4 2 0 Séminaires ANRS – 5/2011 COHVAC

  13. Volunteers presenting VISP (N=25) Séminaires ANRS – 5/2011 COHVAC

  14. VISP - conclusions • More than 60% of recombinant envelope protein recipients remained HIV seropositive more than 16 years after vaccination. • In contrast, vaccine-induced seropositivity was observed only in less than 20% of Alvac canarypox products recipients 8 years after vaccination and beyond. • Long term persistence of vaccine-induced seropositivity should be considered as a possible consequence of HIV preventive vaccine trials and participants informed accordingly. Séminaires ANRS – 5/2011 COHVAC

  15. Self-administered questionnaire Characteristics of volunteers Dec 2008 - Apr 2010 Séminaires ANRS – 5/2011 COHVAC

  16. Socio-economic status and social life * French general population: Insee, Eurostat, Invs data (2006 to 2008) ** 25 to 64 years Séminaires ANRS – 5/2011 COHVAC

  17. Spouse / partner 5 Employer 4 Family 4 Friends 3 Bank or insurance 2 Other 1 Any trial-related problem 13 Experience of trial-related problems 0 50 100% Séminaires ANRS – 5/2011 COHVAC

  18. Regrets or constraints about participating Often Rarely Regrets 2 98 Never Many constraints Constraints Constraints 1 9 42 48 Few constraints No constraints at all 0 20 40 60 80 100% Séminaires ANRS – 5/2011 COHVAC

  19. Factors associated with no-constraints report Route Mucosal 29 50 IM/ID Follow-up < 5.2 y 54 >=5.2 42 High school graduate No 66 Yes 45 Employment No 57 Yes 46 In couple No 55 Yes 45 Very comfortable home No 39 Yes 52 Blood donor No 42 Yes 53 0 20 40 60 80% % reporting no constraints at all Séminaires ANRS – 5/2011 COHVAC

  20. Sexual behaviour Previous 12 months Casual partners Yes 7 174 11 NA No Steady partner No 34 8 Yes NA 1 0 50 100 150 200 Number of volunteers Séminaires ANRS – 5/2011 COHVAC

  21. STEADY PARTNER UNSAFE SEX WITH CASUAL PARTNER CASUAL PARTNERS HIV STATUS UNKNOWN OR POSITIVE Unsafe sex None of the volunteers acquired HIV infection at enrollment Séminaires ANRS – 5/2011 COHVAC

  22. Questionnaires - Conclusions • Regret and perceived negative consequences were infrequent in this group of HIV vaccine trial volunteers • Very few volunteers reported unsafe sex, several years after selection with low HIV risk • Trials well accepted and objectives understood Séminaires ANRS – 5/2011 COHVAC

  23. Limitations • ~60% of eligible participants were tested or returned questionnaires • Different EIA tests were used • Self-administered questionnaire less susceptible to bias of social desirability but limited item non-response (< 5%) Séminaires ANRS – 5/2011 COHVAC

  24. Perspectives • Relations VISP / negative consequences  Abstract submitted to AIDS Vaccine 2011 conference • HIV testing in volunteers ? • Questionnaire for non-participants • End of inclusions for past trials expected by 2011 • Open cohort for future trials Séminaires ANRS – 5/2011 COHVAC

  25. ANRS COV1-COHVAC Acknowledgments to all the volunteers

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