Infection, Precancerous Condition
Conditions
Keywords
infection, low-grade squamous intraepithelial lesion, atypical squamous cells of undetermined significance
Brief summary
RATIONALE: Vaccines made from human papillomavirus may help the body build an effective immune response to kill HIV cells. PURPOSE: This phase II trial is studying the side effects and how well human papillomavirus vaccine therapy works in treating men with HIV-1 infection.
Detailed description
OBJECTIVES: Primary * To assess the safety and tolerability of quadrivalent human papillomavirus (HPV) (types 6, 11, 16, 18) recombinant vaccine in HIV-infected men. * To assess the immunogenicity of the quadrivalent HPV vaccine for types 6, 11, 16 and 18 in subjects who are antibody-negative at baseline. Secondary * To evaluate the changes in plasma HIV-1 RNA and CD4+ count after the vaccination series. * To describe the associations of CD4+ count, nadir CD4+ count, and age on antibody response. * To evaluate the levels and persistence of HPV 6, 11, 16, and 18 antibody titers after the vaccination series among subjects according to serostatus at baseline. * To evaluate the oral levels of serum IgA before and after the vaccination series. Tertiary * To evaluate prevalent and incident HPV infections in the anal canal. * To evaluate cytological and histological abnormalities in the anal canal. * To evaluate prevalent and incident HPV infections in the oral cavity. * To compare oral and anal compartmental shedding of HPV before and after vaccination. OUTLINE: This is a multicenter study. Patients receive quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine intramuscularly on day 0 and weeks 8 and 24. After completion of protocol therapy, patients are followed at 7, 12, and 18 months.
Interventions
BIOLOGICALGardasil
week 0, 8, 24, 128
Sponsors
National Cancer Institute (NCI)
The Emmes Company, LLC
AIDS Malignancy Consortium
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: Inclusion criteria: * HIV-1 infection, as documented by any licensed ELISA test kit and confirmed by western blot prior to study entry * HIV-1 culture, HIV-1 antigen, plasma HIV-1 RNA, or a second antibody test by a method other than ELISA is acceptable as an alternative confirmatory test * Anal human papilloma virus DNA PCR-negative for either type 16 and/or type 18 within 90 days prior to entry * If receiving antiretroviral therapy: * Receipt of antiretroviral therapy for at least 6 months prior to entry * No change in antiretroviral therapy within 30 days prior to entry * CD4 cell count \> 200 cells/mm³ within 90 days prior to study entry * HIV-1 RNA \< 200 copies/mL within 90 days prior to entry * If not receiving antiretroviral therapy: * CD4 cell count ≥ 350 cells/mm³ within 90 days prior to study entry * No plans to start antiretroviral therapy prior to week 28 * Normal anal cytological result, or atypical squamous cell of undetermined significance or low-grade squamous intraepithelial lesions (SIL) result within 90 days prior to entry
Exclusion criteria
* Current or history of anal or perianal carcinoma * Anal cytological result of high-grade SIL (HSIL), atypical squamous cells suggestive of HSIL, or suggestive of invasive carcinoma at screening or a history of these results * Presence of high-grade anal intraepithelial neoplasm (HGAIN) (e.g., AIN 2 or 3, or perianal intraepithelial neoplasia grade 2 or 3), or invasive carcinoma at pre-entry, or history of HGAIN * Current or history of anal or peri-anal condyloma is allowed PATIENT CHARACTERISTICS: Inclusion criteria: * Karnofsky performance status 70-100% * Absolute neutrophil count \> 750 cells/mm³ * Hemoglobin ≥ 9.0 g/dL * Platelet count ≥ 100,000/mm³ * Creatinine clearance ≥ 60 mL/min * AST and ALT ≤ 3 times ULN * Total or conjugated (direct) bilirubin ≤ 2.5 times ULN
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of ≥ Grade 3 Adverse Events Probably or Definitely Related to the Vaccine | All study visits | Occurrence of grade 3+ adverse events that are at least probably and definitely related to the vaccine |
| Detectable Human Papillomavirus (HPV) Antibody to Type 6 a Month After the Completion of HPV Vaccination Series (Week 28) Among Patients Seronegative for Type 6 at Baseline | Week 28 | — |
| Detectable Human Papillomavirus (HPV) Antibody to Type 11 a Month After the Completion of HPV Vaccination Series (Week 28) Among Patients Seronegative for Type 11 at Baseline | Week 28 | — |
| Detectable Human Papillomavirus (HPV) Antibody to Type 16 a Month After the Completion of HPV Vaccination Series (Week 28) Among Patients Seronegative for Type 16 at Baseline | Week 28 | — |
| Detectable Human Papillomavirus (HPV) Antibody to Type 18 a Month After the Completion of HPV Vaccination Series (Week 28) Among Patients Seronegative for Type 18 at Baseline | Week 28 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| HPV Antibody Titers to Type 18 at Baseline and Weeks 28 and 76 According to Baseline Seropositive Status | weeks 0, 28, and 76 | HPV antibody titers to type 18 at baseline and weeks 28 and 76 according to baseline seropositive status will measured in Milli-Merck units per milliliters |
| Longitudinal Changes in CD4+ Cell Count From Baseline | Week 0, 4, 12, 28 | CD4+ cell count at week 0 was subtracted from CD4+ cell counts at each of weeks 4, 12, and 28. |
| Evaluate Oral Levels of Serum IgA Before and After the Vaccination Series | Weeks 0, 28 and 76 | — |
| Longitudinal Changes in Plasma HIV-1 RNA From Baseline | Week 0, 4, 12, 28 | Plasma HIV-1 RNA at week 0 was subtracted from plasma HIV-1 RNA at each of weeks 4, 12, and 28. |
| HPV Antibody Titers to Type 6 at Baseline and Weeks 28 and 76 According to Baseline Seropositive Status | weeks 0, 28, and 76 | HPV antibody titers to type 6 at baseline and weeks 28 and 76 according to baseline seropositive status will measured in Milli-Merck units per milliliters |
| HPV Antibody Titers to Type 11 at Baseline and Weeks 28 and 76 According to Baseline Seropositive Status | weeks 0, 28, and 76 | HPV antibody titers to type 11 at baseline and weeks 28 and 76 according to baseline seropositive status will measured in Milli-Merck units per milliliters |
| HPV Antibody Titers to Type 16 at Baseline and Weeks 28 and 76 According to Baseline Seropositive Status | weeks 0, 28, and 76 | HPV antibody titers to type 16 at baseline and weeks 28 and 76 according to baseline seropositive status will measured in Milli-Merck units per milliliters |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Gardasil Quadrivalent HPV Vaccine (types 6, 11, 16, 18) for intramuscular injection at study entry, week 8, week 24, and week 128. | 109 |
| Total | 109 |
Baseline characteristics
| Characteristic | Gardasil |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 109 Participants |
| Age, Continuous | 43.4 years STANDARD_DEVIATION 9.4 |
| Region of Enrollment United States | 109 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 109 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 56 / 109 |
| serious Total, serious adverse events | 5 / 109 |
Outcome results
Primary
Detectable Human Papillomavirus (HPV) Antibody to Type 11 a Month After the Completion of HPV Vaccination Series (Week 28) Among Patients Seronegative for Type 11 at Baseline
Time frame: Week 28
Population: Per protocol population for a given HPV type requires patients to be seronegative for that type at entry and to have no HPV DNA detected by PCR for that type at entry and screening. Also, patients must have received 3 doses of vaccine.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gardasil | Detectable Human Papillomavirus (HPV) Antibody to Type 11 a Month After the Completion of HPV Vaccination Series (Week 28) Among Patients Seronegative for Type 11 at Baseline | 0.99 proportion of participants |
Primary
Detectable Human Papillomavirus (HPV) Antibody to Type 16 a Month After the Completion of HPV Vaccination Series (Week 28) Among Patients Seronegative for Type 16 at Baseline
Time frame: Week 28
Population: Per protocol population for a given HPV type requires patients to be seronegative for that type at entry and to have no HPV DNA detected by PCR for that type at entry and screening. Also, patients must have received 3 doses of vaccine.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gardasil | Detectable Human Papillomavirus (HPV) Antibody to Type 16 a Month After the Completion of HPV Vaccination Series (Week 28) Among Patients Seronegative for Type 16 at Baseline | 1.00 proportion of participants |
Primary
Detectable Human Papillomavirus (HPV) Antibody to Type 18 a Month After the Completion of HPV Vaccination Series (Week 28) Among Patients Seronegative for Type 18 at Baseline
Time frame: Week 28
Population: Per protocol population for a given HPV type requires patients to be seronegative for that type at entry and to have no HPV DNA detected by PCR for that type at entry and screening. Also, patients must have received 3 doses of vaccine.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gardasil | Detectable Human Papillomavirus (HPV) Antibody to Type 18 a Month After the Completion of HPV Vaccination Series (Week 28) Among Patients Seronegative for Type 18 at Baseline | 0.95 proportion of participants |
Primary
Detectable Human Papillomavirus (HPV) Antibody to Type 6 a Month After the Completion of HPV Vaccination Series (Week 28) Among Patients Seronegative for Type 6 at Baseline
Time frame: Week 28
Population: Per protocol population for a given HPV type requires patients to be seronegative for that type at entry and to have no HPV DNA detected by PCR for that type at entry and screening. Also, patients must have received 3 doses of vaccine.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gardasil | Detectable Human Papillomavirus (HPV) Antibody to Type 6 a Month After the Completion of HPV Vaccination Series (Week 28) Among Patients Seronegative for Type 6 at Baseline | 0.98 proportion of participants |
Primary
Occurrence of ≥ Grade 3 Adverse Events Probably or Definitely Related to the Vaccine
Occurrence of grade 3+ adverse events that are at least probably and definitely related to the vaccine
Time frame: All study visits
Population: Intention to treat (i.e., received at least one dose of the vaccine)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gardasil | Occurrence of ≥ Grade 3 Adverse Events Probably or Definitely Related to the Vaccine | 0 participants |
Secondary
Evaluate Oral Levels of Serum IgA Before and After the Vaccination Series
Time frame: Weeks 0, 28 and 76
Population: Samples for this outcome measure were not analyzed due to loss of funding for the central lab.
Secondary
HPV Antibody Titers to Type 11 at Baseline and Weeks 28 and 76 According to Baseline Seropositive Status
HPV antibody titers to type 11 at baseline and weeks 28 and 76 according to baseline seropositive status will measured in Milli-Merck units per milliliters
Time frame: weeks 0, 28, and 76
Population: Intent to treat population, includes all participants who received at least one dose of vaccine
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Gardasil | HPV Antibody Titers to Type 11 at Baseline and Weeks 28 and 76 According to Baseline Seropositive Status | Seropositive Group at Baseline | 53 Milli-Merck units/mL |
| Gardasil | HPV Antibody Titers to Type 11 at Baseline and Weeks 28 and 76 According to Baseline Seropositive Status | Seropositive Group at Week 28 | 1536 Milli-Merck units/mL |
| Gardasil | HPV Antibody Titers to Type 11 at Baseline and Weeks 28 and 76 According to Baseline Seropositive Status | Seropositive Group at Week 76 | 797 Milli-Merck units/mL |
| Gardasil | HPV Antibody Titers to Type 11 at Baseline and Weeks 28 and 76 According to Baseline Seropositive Status | Seronegative Group at Baseline | 5 Milli-Merck units/mL |
| Gardasil | HPV Antibody Titers to Type 11 at Baseline and Weeks 28 and 76 According to Baseline Seropositive Status | Seronegative Group at Week 28 | 503 Milli-Merck units/mL |
| Gardasil | HPV Antibody Titers to Type 11 at Baseline and Weeks 28 and 76 According to Baseline Seropositive Status | Seronegative Group at Week 76 | 196 Milli-Merck units/mL |
Secondary
HPV Antibody Titers to Type 16 at Baseline and Weeks 28 and 76 According to Baseline Seropositive Status
HPV antibody titers to type 16 at baseline and weeks 28 and 76 according to baseline seropositive status will measured in Milli-Merck units per milliliters
Time frame: weeks 0, 28, and 76
Population: Intent to treat population, includes all participants who received at least one dose of vaccine
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Gardasil | HPV Antibody Titers to Type 16 at Baseline and Weeks 28 and 76 According to Baseline Seropositive Status | Seropositive Group at Baseline | 83 Milli-Merck units/mL |
| Gardasil | HPV Antibody Titers to Type 16 at Baseline and Weeks 28 and 76 According to Baseline Seropositive Status | Seropositive Group at Week 28 | 2005 Milli-Merck units/mL |
| Gardasil | HPV Antibody Titers to Type 16 at Baseline and Weeks 28 and 76 According to Baseline Seropositive Status | Seropositive Group at Week 76 | 1225 Milli-Merck units/mL |
| Gardasil | HPV Antibody Titers to Type 16 at Baseline and Weeks 28 and 76 According to Baseline Seropositive Status | Seronegative Group at Baseline | 6 Milli-Merck units/mL |
| Gardasil | HPV Antibody Titers to Type 16 at Baseline and Weeks 28 and 76 According to Baseline Seropositive Status | Seronegative Group at Week 28 | 1001 Milli-Merck units/mL |
| Gardasil | HPV Antibody Titers to Type 16 at Baseline and Weeks 28 and 76 According to Baseline Seropositive Status | Seronegative Group at Week 76 | 287 Milli-Merck units/mL |
Secondary
HPV Antibody Titers to Type 18 at Baseline and Weeks 28 and 76 According to Baseline Seropositive Status
HPV antibody titers to type 18 at baseline and weeks 28 and 76 according to baseline seropositive status will measured in Milli-Merck units per milliliters
Time frame: weeks 0, 28, and 76
Population: Intent to treat population, includes all participants who received at least one dose of vaccine
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Gardasil | HPV Antibody Titers to Type 18 at Baseline and Weeks 28 and 76 According to Baseline Seropositive Status | Seropositive Group at Baseline | 53 Milli-Merck units/mL |
| Gardasil | HPV Antibody Titers to Type 18 at Baseline and Weeks 28 and 76 According to Baseline Seropositive Status | Seropositive Group at Week 28 | 765 Milli-Merck units/mL |
| Gardasil | HPV Antibody Titers to Type 18 at Baseline and Weeks 28 and 76 According to Baseline Seropositive Status | Seropositive Group at Week 76 | 370 Milli-Merck units/mL |
| Gardasil | HPV Antibody Titers to Type 18 at Baseline and Weeks 28 and 76 According to Baseline Seropositive Status | Seronegative Group at Baseline | 5 Milli-Merck units/mL |
| Gardasil | HPV Antibody Titers to Type 18 at Baseline and Weeks 28 and 76 According to Baseline Seropositive Status | Seronegative Group at Week 28 | 181 Milli-Merck units/mL |
| Gardasil | HPV Antibody Titers to Type 18 at Baseline and Weeks 28 and 76 According to Baseline Seropositive Status | Seronegative Group at Week 76 | 38 Milli-Merck units/mL |
Secondary
HPV Antibody Titers to Type 6 at Baseline and Weeks 28 and 76 According to Baseline Seropositive Status
HPV antibody titers to type 6 at baseline and weeks 28 and 76 according to baseline seropositive status will measured in Milli-Merck units per milliliters
Time frame: weeks 0, 28, and 76
Population: Intent to treat population, includes all participants who received at least one dose of vaccine
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Gardasil | HPV Antibody Titers to Type 6 at Baseline and Weeks 28 and 76 According to Baseline Seropositive Status | Seropositive Group at Baseline | 76 Milli-Merck units/mL |
| Gardasil | HPV Antibody Titers to Type 6 at Baseline and Weeks 28 and 76 According to Baseline Seropositive Status | Seropositive Group at Week 28 | 933 Milli-Merck units/mL |
| Gardasil | HPV Antibody Titers to Type 6 at Baseline and Weeks 28 and 76 According to Baseline Seropositive Status | Seropositive Group at Week 76 | 613 Milli-Merck units/mL |
| Gardasil | HPV Antibody Titers to Type 6 at Baseline and Weeks 28 and 76 According to Baseline Seropositive Status | Seronegative Group at Baseline | 5 Milli-Merck units/mL |
| Gardasil | HPV Antibody Titers to Type 6 at Baseline and Weeks 28 and 76 According to Baseline Seropositive Status | Seronegative Group at Week 28 | 336 Milli-Merck units/mL |
| Gardasil | HPV Antibody Titers to Type 6 at Baseline and Weeks 28 and 76 According to Baseline Seropositive Status | Seronegative Group at Week 76 | 146 Milli-Merck units/mL |
Secondary
Longitudinal Changes in CD4+ Cell Count From Baseline
CD4+ cell count at week 0 was subtracted from CD4+ cell counts at each of weeks 4, 12, and 28.
Time frame: Week 0, 4, 12, 28
Population: Intention to treat population, includes all participants who received at least one dose of vaccine and had assessments at week 0 and the specified week.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Gardasil | Longitudinal Changes in CD4+ Cell Count From Baseline | Change from baseline at week 4 | 11 cells/uL |
| Gardasil | Longitudinal Changes in CD4+ Cell Count From Baseline | Change from baseline at week 12 | 9 cells/uL |
| Gardasil | Longitudinal Changes in CD4+ Cell Count From Baseline | Change from baseline at week 28 | 1 cells/uL |
Secondary
Longitudinal Changes in Plasma HIV-1 RNA From Baseline
Plasma HIV-1 RNA at week 0 was subtracted from plasma HIV-1 RNA at each of weeks 4, 12, and 28.
Time frame: Week 0, 4, 12, 28
Population: Intention to treat population, includes all participants who received at least one dose of vaccine and had assessments at week 0 and the specified week.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Gardasil | Longitudinal Changes in Plasma HIV-1 RNA From Baseline | Baseline | 38 copies/ml |
| Gardasil | Longitudinal Changes in Plasma HIV-1 RNA From Baseline | Change at 4 weeks from the baseline | 0 copies/ml |
| Gardasil | Longitudinal Changes in Plasma HIV-1 RNA From Baseline | Change at 12 weeks from the baseline | 0 copies/ml |
| Gardasil | Longitudinal Changes in Plasma HIV-1 RNA From Baseline | Change at 28 weeks from the baseline | 0 copies/ml |