A Phase I Study of Quadrivalent Human Papilloma Virus (HPV) (Types 6, 11, 16, 18) Recombinant Vaccine in HIV-Infected and HIV-Negative Pre-Adolescents, Adolescents, and Young Adults

• ELIGIBILITY CRITERIA:

Cohort 1 Inclusion and Exclusion Eligibility Criteria:

INCLUSION CRITERIA:

2.1.1.1 Age 12 to 26 years

2.1.1.2 Females and males

2.1.1.3 HIV-positive

2.1.1.4 CD4 cell count and HIV-1 RNA level parameters

• CD4 cell count greater than or equal to 350 cells/mm(3)
• HIV-1 RNA level by RT PCR less than or equal to 20,000 copies/ml

2.1.1.5 On stable HAART regimen for greater than or equal to 6 months with CD4 and viral load parameters as outlined in 2.1.1.4

2.1.1.6 Patients greater than or equal to 18 years willing to provide informed consent or parent/guardian willing to provide informed consent for minor children less than 18 years of age.

2.1.1.7 Informed assent for patients 12-17 years of age (Optional at the discretion of the Principal Investigator and Parent/Guardian based on maturity level of minor)

2.1.1.8 Willing to use acceptable forms of contraception, if applicable, or abstinence to prevent pregnancy.

EXCLUSION CRITERIA:

2.1.1.9 Any of the following hematologic abnormalities

• Hemoglobin less than 10.0 g/dL
• Neutrophil count less than 1500/mm(3)
• Platelet count less than 75,000/mm(3)
• PT or PTT greater than or equal to 1.5 times ULN (with the exception of patients with known clotting disorders or known lupus anticoagulant).

2.1.1.10 Any of the following hepatic abnormalities

• ALT/SGPT and/or AST/SGOT greater than 2.5 times ULN
• Total bilirubin greater than 1.5 times ULN unless attributable to protease inhibitor therapy.

2.1.1.11 Positive tests (antibody and/or antigen) for hepatitis B and hepatitis C viruses, unless the result is consistent with prior vaccination or prior infection with full recovery.

2.1.1.12 Acute infection requiring therapy at time of enrollment. Participants may be eligible for study after being on stable and appropriate anti-infective therapy.

2.1.1.13 Chemotherapy for active cancer.

2.1.1.14 Documented history of non-adherence to antiretroviral treatment regimen within 12 months of study entry.

2.1.1.15 Pregnancy or breastfeeding.

2.1.1.16 Use of immunosuppressive or immunomodulating agents within 8 weeks of study enrollment. Note: patients receiving oral corticosteroids for management of asthma or contact hypersensitivity for less than or equal to 14 days in duration will be allowed to enroll as long as it has been greater than or equal to 30 days since oral corticosteroid administration.

2.1.1.17 Known immediate hypersensitivity to yeast or any of the vaccine components.

2.1.1.18 Use of investigational agents within 4 weeks prior to study enrollment.

2.1.1.19 Active external genital warts requiring treatment or CIN2/3

2.1.1.20 Any clinically significant diseases (other than HIV infection) or findings during study screening that, in the opinion of the Principal Investigator or Lead Associate Investigator, may interfere with the study.

Cohort 2 Inclusion and Exclusion Eligibility Criteria:

Inclusion Criteria

2.1.2.1 Age 12 to 26 years

2.1.2.2 Females and males

2.1.2.3 HIV-positive

2.1.2.4 CD4 cell count and HIV-1 RNA level parameters

• CD4 cell count greater than or equal to 500 cells/mm(3)
• HIV-1 RNA level by RT PCR less than or equal to 20,000 copies/ml.

2.1.2.5 Not receiving antiretroviral treatment with CD4 and viral load parameters as outlined in 2.1.2.4.

2.1.2.6 Patients greater than or equal to 18 years willing to provide informed consent or parent/guardian willing to provide informed consent for minor children less than 18 years of age.

2.1.2.7 Informed assent for patients 12-17 years of age (Optional at the discretion of the Principal Investigator and Parent/Guardian based on maturity level of minor)

2.1.2.8 Willing to use acceptable forms of contraception, if applicable, or abstinence to prevent pregnancy.

EXCLUSION CRITERIA:

2.1.2.9 Any of the following hematologic abnormalities:

• Hemoglobin less than 10.0 g/dL
• Neutrophil count less than 1500/mm(3)
• Platelet count less than 75,000/mm(3)
• PT or PTT greater than or equal to 1.5 times ULN (with the exception of patients with known clotting disorders or known lupus anticoagulant).

2.1.2.10 Any of the following hepatic abnormalities

• ALT/SGPT and/or AST/SGOT greater than 2.5 times ULN
• Total bilirubin greater than 1.5 times ULN unless attributable to protease inhibitor therapy.

2.1.2.11 Positive tests (antibody and/or antigen) for hepatitis B and hepatitis C viruses, unless the result is consistent with prior vaccination or prior infection with full recovery.

2.1.2.12 Acute infection requiring therapy at time of enrollment. Participants may be eligible for study after being on stable and appropriate anti-infective therapy.

2.1.2.13 Chemotherapy for active cancer.

2.1.2.14 Pregnancy or breastfeeding.

2.1.2.15 Use of immunosuppressive or immunomodulating agents within 8 weeks prior to study enrollment. Note: patients receiving oral corticosteroids for management of asthma or contact hypersensitivity for less than or equal to 14 days in duration will be allowed to enroll as long as it has been greater than or equal to 30 days since oral corticosteroid administration.

2.1.2.16 Known immediate hypersensitivity to yeast or any of the vaccine components.

2.1.2.17 Use of investigational agents within 4 weeks prior to study enrollment.

2.1.2.18 Active external genital warts requiring treatment or CIN2/3

2.1.2.19 Any clinically significant diseases (other than HIV infection) or findings during study screening that, in the opinion of the Principal Investigator or Lead Associate Investigator may interfere with the study.

Cohort 3 Inclusion and Exclusion Eligibility Criteria:

INCLUSION CRITERIA:

2.1.3.1 Age 12 to 26 years

2.1.3.2 Females and males

2.1.3.3 HIV-negative

2.1.3.4 Patients greater than or equal to 18 years willing to provide informed consent or parent/guardian willing to provide informed consent for minor children less than 18 years of age.

2.1.3.5 Informed assent for patients 12-17 years of age (Optional at the discretion of the Principal Investigator and Parent/Guardian based on maturity level of minor)

2.1.3.6 Willing to use acceptable forms of contraception, if applicable, or abstinence to prevent pregnancy.

EXCLUSION CRITERIA:

2.1.3.7 Any of the following hematologic abnormalities:

• Hemoglobin less than 10.0 g/dL
• Neutrophil count less than 1500/mm(3)
• Platelet count less than 75,000/mm(3)
• PT or PTT greater than or equal to 1.5 times ULN (with the exception of patients with known clotting disorders or known lupus anticoagulant).

2.1.3.8 Any of the following hepatic abnormalities

• ALT/SGPT and/or AST/SGOT greater than 2.5 times ULN
• Total Bilirubin greater than 1.5 times ULN unless attributable to protease inhibitor therapy.

2.1.3.9 Positive tests (antibody and/or antigen) for HIV, hepatitis B and hepatitis C viruses, unless the result is consistent with prior vaccination or prior infection with full recovery.

2.1.3.10 Acute infection requiring therapy at time of enrollment. Participants may be eligible for study after being on stable and appropriate anti-infective therapy.

2.1.3.11 Chemotherapy for active cancer.

2.1.3.12 Pregnancy or breastfeeding

2.1.3.13 Use of immunosuppressive or immunomodulating agents within 8 weeks prior to study enrollment. Note: patients receiving oral corticosteroids for management of asthma or contact hypersensitivity for less than or equal to 14 days in duration will be allowed to enroll as long as it has been greater than or equal to 30 days since oral corticosteroid administration.

2.1.3.14 Known immediate hypersensitivity to yeast or any of the vaccine components.

2.1.3.15 Use of investigational agents within 4 weeks prior to study enrollment.

2.1.3.16 Active external genital warts requiring treatment or CIN2/3

2.1.3.17 Any clinically significant diseases or findings during study screening that, in the opinion of the Principal Investigator or Lead Associate Investigator may interfere with the study.