This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Pediatric Aids Clinical Trials Group (PACTG) 1047 is a phase II, double blind, placebo controlled study of the safety and immunogenicity of Quadrivalant Human Papilloma virus (QHPV) vaccine in a population of Human Immunodeficiency Virus (HIV)-1 infected boys and girls aged 7 years to under 12 years. The vaccine, also known as Gardasilwas developed by Merck Labs with the target viral types being 6, 11, 16, and 18. The most common oncogenic Human Papillomavirus (HPV) types that cause cervical dysplasia and cancer, in both HIV-infected and uninfected women, are HPV 16 and 18. The most common types of HPV, causing genital warts, are types 6 and 11. On May 18, 2006, an advisory committee for the Federal Drug Administration (FDA) reviewed Merck's application for licensure of Gardasil . It is expected that the vaccine will receive approval in early June, 2006. However, no HIV-infected children, or children with other immune compromising conditions, have been enrolled or received monovalent or quadrivalent HPV vaccine in any clinical trials.The incidence of cervical cancer in HIV-infected women increases as immune competence decreases with progression of HIV disease. Cervical cancer is more extensive and more difficult to cure in HIV-infected women than in HIV-uninfected women and the recurrence rate after standard clinical care is higher. In addition, HIV-infected individuals are at increased risk for penile and anal cancer, including individuals who do not report prior anal intercourse. Because HPV is a sexually transmitted infection, prevention in women will be enhanced by prevention in their partners as well. Thus, evaluation of a prophylactic vaccine, which might protect HIV-infected girls and boys from infection with the most common HPV types that cause anogenital dysplasia and external genital lesions, is an important scientific goal.The study population will consist of 120 HIV-1 infected children recruited from multiple PACTG sites in the U.S. This protocol will be undertaken in children > 7 to < 12 years of age because it is likely that this preventative vaccine will be used before children become sexually active. It is expected that, in terms of safety, QHPV Vaccine will be generally well-tolerated in HIV-infected children in this age group. The subjects will be randomly selected to receive the study vaccine or placebo, with 75% receiving the active vaccine and 25% receiving placebo during Stage I of the study. Since it is expected that children with weaker immune status would respond differently from children with stronger immune systems, the population will be stratified into three groups based on their CD4% history and current CD4%. Stage I: After satisfying eligibility criteria including real-time pregnancy testing for menstruating females, the vaccine/placebo is given intramuscularly 3 times (at entry, week 8 and week 24). Subsequent safety assessment consists of at least 30 minutes in the clinic directly after immunization, a day 3 phone evaluation, study visits on week 4, 8, 12, 24, and 28. Subjects will also be asked to keep a record of oral temperature and symptoms following the injections. (See attached Appendix IV, the Vaccination Report Card) Subjects will be strongly encouraged to phone the study nurse or Dr. Salazar should any unusual or alarming symptoms occur. Stage II: At week 96, the groups will be unblinded. If the vaccine has been deemed safe and well tolerated, a fourth dose will be given to those children who had received active QHPV. The placebo group would now begin the regimen of active QHPV and follow up visits. For the group who receives the fourth dose of active QHPV, safety follow up will occur at weeks 97, 100 and 108. Those who begin active QHPV at 96 weeks will be followed in a likewise fashion until study week 124. (Please see attached Appendix 1I A and IB.) Throughout the course of the study, immunogenicity will be evaluated via blood and saliva samples using ELISPOT (anti-HPV CMI), HPV antibody cLIA (Competitive Luminex Immunoassay) and IgG and IgA anti-HPV testing.
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