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Immunogenicity and safety of the HPV-6, -11, -16, -18 Vaccine in Hiv -positive young women

Immunogenicity and safety of the HPV-6, -11, -16, -18 Vaccine in Hiv -positive young women. J. Kahn, J. Xu, B. Kapogiannis, B. Rudy, N. Liu, R. Gonin, C. Wilson, C. Worrell, K. Squires, and the Adolescent Medicine Trials Network for HIV/AIDS Interventions . AIDS 2012 25 July 2012.

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Immunogenicity and safety of the HPV-6, -11, -16, -18 Vaccine in Hiv -positive young women

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  1. Immunogenicity and safety of the HPV-6, -11, -16, -18 Vaccine in Hiv-positive young women J. Kahn, J. Xu, B. Kapogiannis, B. Rudy, N. Liu, R. Gonin, C. Wilson, C. Worrell, K. Squires,and the Adolescent Medicine Trials Network for HIV/AIDS Interventions AIDS 2012 25 July 2012

  2. hpv in hiv-infected individuals • HIV-infected individuals are at increased risk for both HPV infection and progression to HPV-related malignancies such as invasive cervical cancer 1 • Cancers in HIV-infected individuals often more aggressive, less responsive to treatment2 1SerrainoInt J Cancer 1999, Mbulaiteye JAIDS 2003, Ellerbrock JAMA 2007 2 Holcomb GynOncol 1999

  3. hpv vaccination in hiv-infected individuals • Two prophylactic HPV vaccines are FDA-approved • Quadrivalent and bivalent • In healthy individuals, vaccines safe, highly immunogenic, and effective • HPV vaccination could have a substantial public health impact, especially in regions with high burden of HIV • Benefit of vaccinating HIV-infected women uncertain • HPV prevalence is relatively high • Little known about safety and immunogenicity

  4. aims • To define immunogenicity of the quadrivalent (HPV-6, -11, -16, -18) vaccine in HIV-infected young women • To determine whether the quadrivalentvaccine is well-tolerated and safe in HIV-infected young women

  5. Overview of the study • Study design • Phase II, open-label, multi-center trial • Study population • HIV-infected young women 16 to 23 years of age recruited from 14 sites • Study duration • 48 weeks • Subjects received the vaccine at day 1, week 8, and week 24, then followed for 24 weeks • Sample size • 99 subjects

  6. Selected inclusion/exclusion criteria Inclusion • HIV infected after the age of 9 years • Two groups • Group A: ART naïve or no HAART for at least 6 months • Group B: receiving HAART for at least 6 months, with two HIV-1 RNA viral loads < 400 copies/mL Exclusion • Recent anogenital warts or history of CIN 2/3 • Active opportunistic or serious bacterial infection • Immune globulin, blood/plasma products, steroids

  7. Study Procedures • Questionnaires • Laboratory testing • CD4+ count, HIV viral load, CBC, chemistry profile • STI and pregnancy testing • HPV testing (41 types) • Serum antibody titers • Before dose #1 • Before and 4 weeks after dose #3 • 24 weeks after dose #3 • Safety assessed after each vaccine dose • Self-reported AEs and laboratory AEs

  8. Outcome measures • GMTs • Titers (in mMU/mL) to HPV-6, -11, -16, -18, 4 weeks post vaccine dose #3 • Seroconversion rates • Proportion with GMTs to HPV-6, -11, -16, and -18 > 20, 16, 20 and 24 mMU/mL, respectively, 4 weeks post vaccine dose #3 • AE rates • Proportion of subjects experiencing local, systemic, laboratory AEs with each vaccine dose, graded 1 to 4 • 1=mild, 2=moderate, 3=severe, 4=life-threatening

  9. analyses • Immunogenicity • Analyses conducted separately for 4 type-specific antibodies, and subjects seropositive or HPV DNA positive for each type excluded from analysis • One-sample t-test was used to compare GMTs, and Fisher’s exact test was used to compare seroconversion rates, of participants vs. HIV-uninfected historical controls • 16-23 y/o women (N=267) recruited from Brazil, Europe and the U.S.: healthy, no history of abnormal Pap test, < 4 male sex partners (Villa, Vaccine 2006) • Safety and tolerability • Descriptives; evaluated for all participants

  10. participant characteristicsBaseline (N=99) *Subjects in group B vs. group A more likely to have an HIV VL < 400 copies/mL (p<0.0001)

  11. Subjects HPV Seronegative and hpvdna negative at baseline Immunogenicity results pertain only to these subjects

  12. GmtGROUP A SUBJECTS VS. CONTROLS No HAART * Differences in mean GMTs for Group A subjects vs. controls

  13. GmtGROUP B SUBJECTS VS. CONTROLS HAART * Differences in mean GMTs for Group B subjects vs. controls

  14. Seroconversion ratesGroup A SUBJECTS vs. controls No HAART * Differences in seroconversion rates for Group A subjects vs. controls

  15. Seroconversion ratesGroup B SUBJECTS vs. controls HAART * Differences in seroconversion rates for Group B subjects vs. controls

  16. GMT at 28 and 48 weeks HPV-6 Group B Group A Overall 10000 1000 100 10 0 GMT (mMU/mL) 48 28 0 Study week

  17. Seroconversion at 48 weeks * P <.05

  18. tolerability and Safety Subjects with > 1 AE, doses 1, 2, and 3 combined

  19. Tolerability and Safety Subjects with > 1 AE, doses 1, 2, and 3 combined

  20. Laboratory toxicities • No AEs > grade 3 evaluated as definitely related, probably related, or possibly related to vaccine • Qualitative evaluation demonstrated no concerning patterns in CD4+ count or VL

  21. limitations • Small N • Historical controls • Immunogenicity only examined among those seronegative and HPV DNA negative

  22. conclusions • Among HIV-infected young women seronegative and HPV DNA negative at the time of vaccination, HPV type-specific immune responses to vaccination were generally robust; seroconversion rates > 90% • The vaccine was generally well-tolerated and safe • These data support recommendations to: • Vaccinate HIV-infected young women • Target vaccination to 11-12 year-olds, who are less likely to have acquired HIV behaviorally • Research needed re: women who did not seroconvert, long-term efficacy, efficacy in men

  23. acknowledgments • ATN supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), with supplemental funding from NIDA and NIMH (5 U01 HD 40533 and 5 U01 HD 40474) • Vaccine and HPV geometric mean titers provided by Merck & Co., Inc. • Scientific review by the TLG • Logistical support by ATN Coordinating Center • Analytic support by ATN DOC at Westat

  24. Participating ATN sites • Children’s National Medical Center • Children’s Hospital of Philadelphia • John H. Stroger Jr. Hospital, Cook County • University of Puerto Rico • Montefiore Medical Center • Tulane University Health Sciences Center • University of Miami School of Med. • Children’s Diagnostic and Treatment Center • St. Jude’s Children’s Research Hospital • Children’s Memorial • University of South Florida • Children’s Hospital of Los Angeles • Mount Sinai Medical Center • University of Maryland

  25. GMTGroup A vs. Group B * Differences in mean GMTs for group A subjects vs. group B subjects

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