HIV Infections, Sexually Transmitted Diseases
Conditions
Keywords
HPV
Brief summary
The purpose of this study is to determine the safety of and immune response to a new human papillomavirus (HPV) vaccine in HIV (Human immunodeficiency virus) infected children between the ages of 7 and 12 years.
Detailed description
Genital HPV infection is the most common sexually transmitted infection in the world and may lead to genital warts, anogenital dysplasias, and invasive cancers. HIV infected people and others with compromised immunity are at greater risk for HPV-related complications. In particular, researchers are concerned about the risk of HPV infection to women, who may be infected by their male partners, especially if these partners engage in anal intercourse. HIV infected women tend to have multiple types of HPV (associated with a greater risk of HPV-related disease), are less likely to clear HPV-related conditions, and are more likely to progress to HPV-related disease. The quadrivalent HPV (types 6, 11, 16, 18) L1 virus-like particle (VLP) vaccine to be tested in this study was safe and generally well tolerated in previous studies conducted in healthy and HPV-exposed adolescents, young adults, and older women. However, it is still unclear if the vaccine will be safe and will elicit a similar immune response in younger children. The purpose of this study is to evaluate the safety and immunogenicity of the novel quadrivalent HPV (Types 6, 11, 16, 18) L1 VLP vaccine in HIV infected children 7 to 12 years of age. This study had two stages and lasted at least 108 weeks. In Stage I, participants were stratified by CD4 percentage (CD4%) nadir and CD4% at study screening (Stratum A: CD4% Nadir \< 15 and CD4% ≥ 15 at screening, Stratum B: CD4% Nadir ≥ 15 and \< 25 and CD4% ≥ 15 at screening, Stratum C: CD4% Nadir ≥ 25 and CD4% ≥ 25 at screening). Within each stratification group, they were randomly assigned to one of two arms. During Stage I, Arm A (QHPV:Quadrivalent human papillomavirus vaccine) participants received 3 doses of vaccine, while Arm B (Placebo/QHPV) participants received 3 doses of placebo. Participants did not know whether they were receiving vaccine or placebo. Participants received their assigned intervention at study entry and Weeks 8 and 24. At Week 96, Stage II began, and all study participants were told if they received vaccine or placebo in Stage I. Arm A participants received an additional dose of vaccine at Week 96; Arm B participants received doses of vaccine at Weeks 96, 104, and 120. Over the course of the study, there were at least 12 study visits. A physical exam and blood collection occurred at most visits; medical history occurred at selected visits. After each vaccination, participants were observed for at least 30 minutes to monitor for any allergic reactions possibly resulting from the vaccination. For 15 days following vaccination, parents or guardians were asked to complete a report card with details of each child's signs and symptoms. Three days after each vaccination, parents or guardians of study participants were contacted by telephone and asked about any adverse events that a child may have experienced.
Interventions
BIOLOGICALQuadrivalent human papillomavirus (types 6, 11, 16, 18) L1 virus-like particle (VLP) or Quadrivalent human papillomavirus vaccine (QHPV)
QHPV at week 0, 8, 24 and 96.
OTHERPlacebo/QHPV
Placebo at week 0, 8, 24 and QHPV at week 96, 104, 120.
Sponsors
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
7 Years to 12 Years
Healthy volunteers
No
Inclusion criteria
Children ages ≥ 7 to \< 12 years of age. A confirmed diagnosis of HIV infection, defined as two positive assays from two different samples. The two results may be in any combination of the following: * at any age: Deoxyribonucleic acid (DNA) polymerase chain reaction (PCR), Ribonucleic acid (RNA) PCR * age \> 4 weeks: p24 antigen detection * age \>18 months: licensed ELISA (Enzyme-linked immunosorbent assay) with confirmatory Western Blot CD4% ≥ 15 at the time of screening is required (Note that this is a minimum requirement, and that for Stratum C the CD4% needs to be ≥ 25). For Strata A and B: Currently stable (≥ 3 months) on highly active antiretroviral therapy (HAART) regimen, defined as three or more antiretrovirals from at least two different therapeutic classes, or therapy with the combination of azidothymidine, lamivudine, and abacavir. For stratum C no antiretroviral therapy is required. Parent or legal guardian able and willing to provide signed informed consent. Negative urine pregnancy test sensitive to 25 International Unit (IU) beta-human chorionic gonadotropin (HCG) for girls who are menstruating (child bearing potential). Female study volunteers who are participating in sexual activity that could lead to pregnancy must agree to use two reliable methods of contraception, one of which must be a barrier method. A barrier method of contraception (condoms or cervical cap) together with another reliable form of contraception (condoms a , with a spermicidal agent; a diaphragm or cervical cap with spermicide; an intrauterine device \[IUD\]; or hormonal-based contraception) must be used while on this study. Condoms are recommended because their appropriate use is the only contraception method effective for preventing HIV-1 transmission Males participating in the study must not attempt to impregnate a woman, or participate in sperm donation programs. Males engaging in sexual activity that could lead to pregnancy must use a condom.
Exclusion criteria
Body temperature ≥ 101 F or ≥ 38.3 C, orally determined, within 72 hours prior to the first and each subsequent injection. Subjects may be vaccinated any time in the next seven days thereafter, provided that the site investigator is satisfied that the febrile illness has ended. Total bilirubin ≥ 5 x Upper Limit of Normal (ULN) at screening. Alanine transaminase (ALT) or serum glutamic pyruvic transaminase (SGPT) ≥ 5 x ULN at screening in the absence of other explained causes (as determined by the site investigator) at screening. Serum creatinine ≥ 1.5 mg/dL at screening. Absolute neutrophil count ≤ 750 cells/mm3 at screening. Hemoglobin ≤ 9.9 g/dL at screening. Platelet count ≤ 75,000 cells/mm³ at screening. Presence of an acute opportunistic non-bacterial or bacterial infection requiring therapy at the time of enrollment; the subject may be entered once he/she is stable on appropriate anti-infective therapy. Chemotherapy for active malignancy. Other known or suspected disease of the immune system, or immunosuppressive therapy. Prior treatment with immunosuppressive or immunomodulation therapy within 60 days of screening. Prior treatment with three or more week-long courses of corticosteroids (≥ 2.0 mg/kg or ≥ 20 mg total of prednisone-equivalent) within one year of screening; or any systemic (oral or parenteral) steroids (≥ 2.0 mg/kg or ≥ 20 mg total of prednisone-equivalent for ≥ 3 days) within 30 days of study entry. Prior vaccinations with inactivated vaccines received within two weeks of any dose of study vaccine, and no other vaccinations may be planned for two weeks after each dose of study vaccine. Prior vaccinations with live vaccines received within three weeks before any dose of study vaccine, and no other vaccinations may be planned for two weeks after each dose of study vaccine. Prior diagnosis of sexually transmitted infections (STIs), genital warts, or juvenile recurrent papillomatosis. History of any severe allergic reaction (e.g., swelling of the mouth and throat, difficulty breathing, hypotension, or shock) that required medical intervention. Known allergies to any vaccine component, including aluminum, yeast, or BENZONASE™ (nuclease, Nycomed \[used to remove residual nucleic acids from this and other vaccines\]). Previous treatment with any immune globulin preparation or blood-derived products within the six months prior to the first injection and none may be planned during the study. Known coagulation disorder that would contraindicate Intramuscular (IM) injections. Any clinically significant diseases (other than HIV infection) or clinically significant findings during the screening medical history or physical examination that, in the investigator's opinion, would compromise the outcome of this study. Breastfeeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Participants Developing Grade 3 or 4 Adverse Events (AEs) | Within 14 days of first three doses of vaccination | Adverse events were graded using the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events (December 2004). The grades used are: Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Potentially Life-Threatening. All grade 3 and higher signs, symptoms, and laboratory toxicities were included. |
| Percent of Participants Developing Grade 3 or 4 Adverse Events (AEs) Attributed to Study Treatment | Within 14 days of first three doses of vaccination | Adverse events were graded using the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events (December 2004). All grade 3 and higher signs, symptoms, and laboratory toxicities attributed to study treatment were included. The relationship between the Adverse Events and the vaccination were evaluated by study team and assigned to, for example, Treatment related, Non-treatment related, Baseline, Possibly treatment related. |
| Percent of Participants With Human Papillomavirus (HPV) Type-Specific Seroconversion | At week 28 after beginning the vaccination series | Serum anti-HPV 6, 11, 16, and 18 antibody was measured using a competitive Luminex immunoassay (cLIA; reported in milli-Merck Units \[mMU\]/mL). Sero-positivity was defined as an anti-HPV titer ≥20, 16, 20, and 24 mMU/mL, for HPV types 6, 11, 16, and 18, respectively. |
| Serum Anti-HPV Antibody Titers (cLIA) | Arm A week 0, 28, 72, 96, 97, 100; Arm B week 0, 28, 72, 96, 97, 100, 124. | Geometric means of Type-specific Serum anti-HPV antibody titers (cLIA) |
Secondary
| Measure | Time frame |
|---|---|
| CD4 Percent Over Time | Arm A week 0, 8, 12, 24, 28, 72, 96, 100 and 108; Arm B week 0, 8, 12, 24, 28, 72, 96, 100, 104, 108, 120, and 124. |
| HIV-1 Viral Load (Ribonucleic Acid [RNA] Copies/ml) Over Time | Arm A week 0, 8, 12, 24, 28, 72, 96, 100 and 108; Arm B week 0, 8, 12, 24, 28, 72, 96, 100, 104, 108, 120, and 124. |
| CD4 Count Over Time | Arm A week 0, 8, 12, 24, 28, 72, 96, 100 and 108; Arm B week 0, 8, 12, 24, 28, 72, 96, 100, 104, 108, 120, and 124. |
Countries
Puerto Rico, United States
Participant flow
Recruitment details
Between October 11, 2006 and November 22, 2006 130 participants were enrolled at 34 clinical sites from US & Puerto Rico.
Pre-assignment details
Participants were stratified by CD4% criteria. Four participants were randomized but did not receive the study treatment. The study analyses were based on 126 participants who received the study treatment.
Participants by arm
| Arm | Count |
|---|---|
| Arm A QHPV Participants received three doses of the quadrivalent human papillomavirus vaccine (QHPV) (Types 6, 11, 16, 18) at week 0, 8, and 24 and an additional dose at week 96. | 96 |
| Arm B Placebo/QHPV Participants received three doses of the placebo at week 0, 8, and 24 and additional dose of the quadrivalent human papillomavirus vaccine (QHPV) (Types 6, 11, 16, 18) at week 96, 104 and 120. | 30 |
| Total | 126 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Stage I | Not able to attend clinic | 1 | 0 |
| Stage I | Protocol Violation | 1 | 1 |
| Stage II | Lost to Follow-up | 3 | 0 |
| Stage II | Not able to attend clinic | 1 | 0 |
| Stage II | Protocol Violation | 3 | 0 |
| Stage II | Site closing | 2 | 0 |
| Stage II | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Arm B Placebo/QHPV | Total | Arm A QHPV |
|---|---|---|---|
| Age, Continuous | 9.9 years STANDARD_DEVIATION 1.3 | 9.9 years STANDARD_DEVIATION 1.4 | 10.0 years STANDARD_DEVIATION 1.4 |
| CD4% | 35.8 percentage of total lymphocytes STANDARD_DEVIATION 8.6 | 34.3 percentage of total lymphocytes STANDARD_DEVIATION 8.1 | 33.9 percentage of total lymphocytes STANDARD_DEVIATION 7.9 |
| CD4 count | 1013 cells/µL STANDARD_DEVIATION 455 | 903 cells/µL STANDARD_DEVIATION 393 | 868 cells/µL STANDARD_DEVIATION 367 |
| Log10(RNA) | 2.6 Log10(copies/mL) STANDARD_DEVIATION 0.8 | 2.7 Log10(copies/mL) STANDARD_DEVIATION 0.9 | 2.7 Log10(copies/mL) STANDARD_DEVIATION 0.9 |
| Race/Ethnicity, Customized Black, non-Hispanic | 11 participants | 65 participants | 54 participants |
| Race/Ethnicity, Customized Hispanic | 14 participants | 51 participants | 37 participants |
| Race/Ethnicity, Customized Others | 3 participants | 4 participants | 1 participants |
| Race/Ethnicity, Customized White, non-Hispanic | 2 participants | 6 participants | 4 participants |
| RNA group ≤400 copies/mL | 22 participants | 87 participants | 65 participants |
| RNA group 401 to ≤5000 copies/mL | 5 participants | 21 participants | 16 participants |
| RNA group >5000 copies/mL | 3 participants | 18 participants | 15 participants |
| Sex: Female, Male Female | 18 Participants | 71 Participants | 53 Participants |
| Sex: Female, Male Male | 12 Participants | 55 Participants | 43 Participants |
| Stratification groups Stratum A | 10 participants | 41 participants | 31 participants |
| Stratification groups Stratum B | 11 participants | 43 participants | 32 participants |
| Stratification groups Stratum C | 9 participants | 42 participants | 33 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 93 / 96 | 30 / 30 |
| serious Total, serious adverse events | 5 / 96 | 2 / 30 |
Outcome results
Primary
Percent of Participants Developing Grade 3 or 4 Adverse Events (AEs)
Adverse events were graded using the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events (December 2004). The grades used are: Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Potentially Life-Threatening. All grade 3 and higher signs, symptoms, and laboratory toxicities were included.
Time frame: Within 14 days of first three doses of vaccination
Population: Any participant who received at least one study vaccine/placebo were included in the safety analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A QHPV | Percent of Participants Developing Grade 3 or 4 Adverse Events (AEs) | 7.3 percent of participants |
| Arm B Placebo/QHPV | Percent of Participants Developing Grade 3 or 4 Adverse Events (AEs) | 6.7 percent of participants |
p-value: 1Fisher Exact
Primary
Percent of Participants Developing Grade 3 or 4 Adverse Events (AEs) Attributed to Study Treatment
Adverse events were graded using the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events (December 2004). All grade 3 and higher signs, symptoms, and laboratory toxicities attributed to study treatment were included. The relationship between the Adverse Events and the vaccination were evaluated by study team and assigned to, for example, Treatment related, Non-treatment related, Baseline, Possibly treatment related.
Time frame: Within 14 days of first three doses of vaccination
Population: Any participant who received at least one study vaccine/placebo were included in the safety analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A QHPV | Percent of Participants Developing Grade 3 or 4 Adverse Events (AEs) Attributed to Study Treatment | 0 percent of participants |
| Arm B Placebo/QHPV | Percent of Participants Developing Grade 3 or 4 Adverse Events (AEs) Attributed to Study Treatment | 0 percent of participants |
Primary
Percent of Participants With Human Papillomavirus (HPV) Type-Specific Seroconversion
Serum anti-HPV 6, 11, 16, and 18 antibody was measured using a competitive Luminex immunoassay (cLIA; reported in milli-Merck Units \[mMU\]/mL). Sero-positivity was defined as an anti-HPV titer ≥20, 16, 20, and 24 mMU/mL, for HPV types 6, 11, 16, and 18, respectively.
Time frame: At week 28 after beginning the vaccination series
Population: The type-specific results are reported for participants remaining after exclusion of those with protocol violations, unevaluable specimens, or the presence of type-specific sero-positive antibody at baseline.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A QHPV | Percent of Participants With Human Papillomavirus (HPV) Type-Specific Seroconversion | Serotype 6 | 100.0 percent of participants |
| Arm A QHPV | Percent of Participants With Human Papillomavirus (HPV) Type-Specific Seroconversion | Serotype 11 | 100.0 percent of participants |
| Arm A QHPV | Percent of Participants With Human Papillomavirus (HPV) Type-Specific Seroconversion | Serotype 16 | 100.0 percent of participants |
| Arm A QHPV | Percent of Participants With Human Papillomavirus (HPV) Type-Specific Seroconversion | Serotype 18 | 96.7 percent of participants |
| Arm B Placebo/QHPV | Percent of Participants With Human Papillomavirus (HPV) Type-Specific Seroconversion | Serotype 18 | 0.0 percent of participants |
| Arm B Placebo/QHPV | Percent of Participants With Human Papillomavirus (HPV) Type-Specific Seroconversion | Serotype 6 | 0.0 percent of participants |
| Arm B Placebo/QHPV | Percent of Participants With Human Papillomavirus (HPV) Type-Specific Seroconversion | Serotype 16 | 3.7 percent of participants |
| Arm B Placebo/QHPV | Percent of Participants With Human Papillomavirus (HPV) Type-Specific Seroconversion | Serotype 11 | 0.0 percent of participants |
Primary
Serum Anti-HPV Antibody Titers (cLIA)
Geometric means of Type-specific Serum anti-HPV antibody titers (cLIA)
Time frame: Arm A week 0, 28, 72, 96, 97, 100; Arm B week 0, 28, 72, 96, 97, 100, 124.
Population: The type-specific results are reported for participants remaining after exclusion of those with protocol violations, unevaluable specimens, or the presence of type-specific sero-positive antibody at baseline as well as any participants with any missing values at any time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Arm A QHPV | Serum Anti-HPV Antibody Titers (cLIA) | Serotype 18 study entry | 5.1 milli-Merck units [mMU]/mL |
| Arm A QHPV | Serum Anti-HPV Antibody Titers (cLIA) | Serotype 6 week 28 | 544.2 milli-Merck units [mMU]/mL |
| Arm A QHPV | Serum Anti-HPV Antibody Titers (cLIA) | Serotype 6 week 72 | 256.4 milli-Merck units [mMU]/mL |
| Arm A QHPV | Serum Anti-HPV Antibody Titers (cLIA) | Serotype 6 week 96 | 227.9 milli-Merck units [mMU]/mL |
| Arm A QHPV | Serum Anti-HPV Antibody Titers (cLIA) | Serotype 6 week 97 | 1604.8 milli-Merck units [mMU]/mL |
| Arm A QHPV | Serum Anti-HPV Antibody Titers (cLIA) | Serotype 6 week 100 | 2473.6 milli-Merck units [mMU]/mL |
| Arm A QHPV | Serum Anti-HPV Antibody Titers (cLIA) | Serotype 11 study entry | 4.1 milli-Merck units [mMU]/mL |
| Arm A QHPV | Serum Anti-HPV Antibody Titers (cLIA) | Serotype 11 week 28 | 1396.6 milli-Merck units [mMU]/mL |
| Arm A QHPV | Serum Anti-HPV Antibody Titers (cLIA) | Serotype 11 week 72 | 313.1 milli-Merck units [mMU]/mL |
| Arm A QHPV | Serum Anti-HPV Antibody Titers (cLIA) | Serotype 11 week 96 | 286.5 milli-Merck units [mMU]/mL |
| Arm A QHPV | Serum Anti-HPV Antibody Titers (cLIA) | Serotype 11 week 97 | 1931.7 milli-Merck units [mMU]/mL |
| Arm A QHPV | Serum Anti-HPV Antibody Titers (cLIA) | Serotype 11 week 100 | 3611.2 milli-Merck units [mMU]/mL |
| Arm A QHPV | Serum Anti-HPV Antibody Titers (cLIA) | Serotype 16 study entry | 5.5 milli-Merck units [mMU]/mL |
| Arm A QHPV | Serum Anti-HPV Antibody Titers (cLIA) | Serotype 16 week 28 | 5172.5 milli-Merck units [mMU]/mL |
| Arm A QHPV | Serum Anti-HPV Antibody Titers (cLIA) | Serotype 16 week 72 | 1126.4 milli-Merck units [mMU]/mL |
| Arm A QHPV | Serum Anti-HPV Antibody Titers (cLIA) | Serotype 16 week 96 | 1034.5 milli-Merck units [mMU]/mL |
| Arm A QHPV | Serum Anti-HPV Antibody Titers (cLIA) | Serotype 16 week 97 | 6167.8 milli-Merck units [mMU]/mL |
| Arm A QHPV | Serum Anti-HPV Antibody Titers (cLIA) | Serotype 16 week 100 | 11205.6 milli-Merck units [mMU]/mL |
| Arm A QHPV | Serum Anti-HPV Antibody Titers (cLIA) | Serotype 6 study entry | 3.8 milli-Merck units [mMU]/mL |
| Arm A QHPV | Serum Anti-HPV Antibody Titers (cLIA) | Serotype 18 week 28 | 931.2 milli-Merck units [mMU]/mL |
| Arm A QHPV | Serum Anti-HPV Antibody Titers (cLIA) | Serotype 18 week 72 | 148.2 milli-Merck units [mMU]/mL |
| Arm A QHPV | Serum Anti-HPV Antibody Titers (cLIA) | Serotype 18 week 96 | 142.0 milli-Merck units [mMU]/mL |
| Arm A QHPV | Serum Anti-HPV Antibody Titers (cLIA) | Serotype 18 week 97 | 925.7 milli-Merck units [mMU]/mL |
| Arm A QHPV | Serum Anti-HPV Antibody Titers (cLIA) | Serotype 18 week 100 | 1530.7 milli-Merck units [mMU]/mL |
| Arm B Placebo/QHPV | Serum Anti-HPV Antibody Titers (cLIA) | Serotype 11 week 100 | 86.4 milli-Merck units [mMU]/mL |
| Arm B Placebo/QHPV | Serum Anti-HPV Antibody Titers (cLIA) | Serotype 11 week 124 | 1023.0 milli-Merck units [mMU]/mL |
| Arm B Placebo/QHPV | Serum Anti-HPV Antibody Titers (cLIA) | Serotype 18 study entry | 5.0 milli-Merck units [mMU]/mL |
| Arm B Placebo/QHPV | Serum Anti-HPV Antibody Titers (cLIA) | Serotype 16 study entry | 5.5 milli-Merck units [mMU]/mL |
| Arm B Placebo/QHPV | Serum Anti-HPV Antibody Titers (cLIA) | Serotype 18 week 100 | 18.7 milli-Merck units [mMU]/mL |
| Arm B Placebo/QHPV | Serum Anti-HPV Antibody Titers (cLIA) | Serotype 6 study entry | 4.1 milli-Merck units [mMU]/mL |
| Arm B Placebo/QHPV | Serum Anti-HPV Antibody Titers (cLIA) | Serotype 16 week 28 | 5.7 milli-Merck units [mMU]/mL |
| Arm B Placebo/QHPV | Serum Anti-HPV Antibody Titers (cLIA) | Serotype 6 week 28 | 4.5 milli-Merck units [mMU]/mL |
| Arm B Placebo/QHPV | Serum Anti-HPV Antibody Titers (cLIA) | Serotype 18 week 28 | 5.0 milli-Merck units [mMU]/mL |
| Arm B Placebo/QHPV | Serum Anti-HPV Antibody Titers (cLIA) | Serotype 6 week 72 | 4.3 milli-Merck units [mMU]/mL |
| Arm B Placebo/QHPV | Serum Anti-HPV Antibody Titers (cLIA) | Serotype 16 week 72 | 5.5 milli-Merck units [mMU]/mL |
| Arm B Placebo/QHPV | Serum Anti-HPV Antibody Titers (cLIA) | Serotype 6 week 96 | 4.5 milli-Merck units [mMU]/mL |
| Arm B Placebo/QHPV | Serum Anti-HPV Antibody Titers (cLIA) | Serotype 18 week 97 | 7.1 milli-Merck units [mMU]/mL |
| Arm B Placebo/QHPV | Serum Anti-HPV Antibody Titers (cLIA) | Serotype 6 week 97 | 17.1 milli-Merck units [mMU]/mL |
| Arm B Placebo/QHPV | Serum Anti-HPV Antibody Titers (cLIA) | Serotype 16 week 96 | 5.5 milli-Merck units [mMU]/mL |
| Arm B Placebo/QHPV | Serum Anti-HPV Antibody Titers (cLIA) | Serotype 6 week 100 | 79.7 milli-Merck units [mMU]/mL |
| Arm B Placebo/QHPV | Serum Anti-HPV Antibody Titers (cLIA) | Serotype 6 week 124 | 678.8 milli-Merck units [mMU]/mL |
| Arm B Placebo/QHPV | Serum Anti-HPV Antibody Titers (cLIA) | Serotype 18 week 72 | 5.0 milli-Merck units [mMU]/mL |
| Arm B Placebo/QHPV | Serum Anti-HPV Antibody Titers (cLIA) | Serotype 11 study entry | 4.0 milli-Merck units [mMU]/mL |
| Arm B Placebo/QHPV | Serum Anti-HPV Antibody Titers (cLIA) | Serotype 16 week 97 | 12.1 milli-Merck units [mMU]/mL |
| Arm B Placebo/QHPV | Serum Anti-HPV Antibody Titers (cLIA) | Serotype 11 week 28 | 4.2 milli-Merck units [mMU]/mL |
| Arm B Placebo/QHPV | Serum Anti-HPV Antibody Titers (cLIA) | Serotype 18 week 124 | 734.3 milli-Merck units [mMU]/mL |
| Arm B Placebo/QHPV | Serum Anti-HPV Antibody Titers (cLIA) | Serotype 11 week 72 | 4.1 milli-Merck units [mMU]/mL |
| Arm B Placebo/QHPV | Serum Anti-HPV Antibody Titers (cLIA) | Serotype 16 week 100 | 142.6 milli-Merck units [mMU]/mL |
| Arm B Placebo/QHPV | Serum Anti-HPV Antibody Titers (cLIA) | Serotype 11 week 96 | 4.0 milli-Merck units [mMU]/mL |
| Arm B Placebo/QHPV | Serum Anti-HPV Antibody Titers (cLIA) | Serotype 16 week 124 | 4113.8 milli-Merck units [mMU]/mL |
| Arm B Placebo/QHPV | Serum Anti-HPV Antibody Titers (cLIA) | Serotype 11 week 97 | 11.8 milli-Merck units [mMU]/mL |
| Arm B Placebo/QHPV | Serum Anti-HPV Antibody Titers (cLIA) | Serotype 18 week 96 | 5.0 milli-Merck units [mMU]/mL |
Secondary
CD4 Count Over Time
Time frame: Arm A week 0, 8, 12, 24, 28, 72, 96, 100 and 108; Arm B week 0, 8, 12, 24, 28, 72, 96, 100, 104, 108, 120, and 124.
Population: Any participant who received at least one study vaccine/placebo and with non-missing CD4 counts at the respective time point.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Arm A QHPV | CD4 Count Over Time | CD4 count at study entry | 868 cells/µL |
| Arm A QHPV | CD4 Count Over Time | CD4 count at week 8 | 907 cells/µL |
| Arm A QHPV | CD4 Count Over Time | CD4 count at week 12 | 906 cells/µL |
| Arm A QHPV | CD4 Count Over Time | CD4 count at week 24 | 864 cells/µL |
| Arm A QHPV | CD4 Count Over Time | CD4 count at week 28 | 875 cells/µL |
| Arm A QHPV | CD4 Count Over Time | CD4 count at week 72 | 823 cells/µL |
| Arm A QHPV | CD4 Count Over Time | CD4 count at week 96 | 781 cells/µL |
| Arm A QHPV | CD4 Count Over Time | CD4 count at week 100 | 831 cells/µL |
| Arm A QHPV | CD4 Count Over Time | CD4 count at week 108 | 839 cells/µL |
| Arm B Placebo/QHPV | CD4 Count Over Time | CD4 count at week 28 | 959 cells/µL |
| Arm B Placebo/QHPV | CD4 Count Over Time | CD4 count at week 124 | 920 cells/µL |
| Arm B Placebo/QHPV | CD4 Count Over Time | CD4 count at week 72 | 933 cells/µL |
| Arm B Placebo/QHPV | CD4 Count Over Time | CD4 count at week 108 | 980 cells/µL |
| Arm B Placebo/QHPV | CD4 Count Over Time | CD4 count at study entry | 1013 cells/µL |
| Arm B Placebo/QHPV | CD4 Count Over Time | CD4 count at week 96 | 874 cells/µL |
| Arm B Placebo/QHPV | CD4 Count Over Time | CD4 count at week 8 | 1018 cells/µL |
| Arm B Placebo/QHPV | CD4 Count Over Time | CD4 count at week 120 | 931 cells/µL |
| Arm B Placebo/QHPV | CD4 Count Over Time | CD4 count at week 12 | 1056 cells/µL |
| Arm B Placebo/QHPV | CD4 Count Over Time | CD4 count at week 100 | 924 cells/µL |
| Arm B Placebo/QHPV | CD4 Count Over Time | CD4 count at week 24 | 993 cells/µL |
| Arm B Placebo/QHPV | CD4 Count Over Time | CD4 count at week 104 | 929 cells/µL |
Secondary
CD4 Percent Over Time
Time frame: Arm A week 0, 8, 12, 24, 28, 72, 96, 100 and 108; Arm B week 0, 8, 12, 24, 28, 72, 96, 100, 104, 108, 120, and 124.
Population: Any participant who received at least one study vaccine/placebo and with non-missing CD4%.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Arm A QHPV | CD4 Percent Over Time | CD4 percent at week 8 | 34 percentage of total lymphocytes |
| Arm A QHPV | CD4 Percent Over Time | CD4 percent at week 96 | 33 percentage of total lymphocytes |
| Arm A QHPV | CD4 Percent Over Time | CD4 percent at week 24 | 34 percentage of total lymphocytes |
| Arm A QHPV | CD4 Percent Over Time | CD4 percent at week 100 | 35 percentage of total lymphocytes |
| Arm A QHPV | CD4 Percent Over Time | CD4 percent at study entry | 34 percentage of total lymphocytes |
| Arm A QHPV | CD4 Percent Over Time | CD4 percent at week 28 | 34 percentage of total lymphocytes |
| Arm A QHPV | CD4 Percent Over Time | CD4 percent at week 12 | 35 percentage of total lymphocytes |
| Arm A QHPV | CD4 Percent Over Time | CD4 percent at week 72 | 33 percentage of total lymphocytes |
| Arm A QHPV | CD4 Percent Over Time | CD4 percent at week 108 | 35 percentage of total lymphocytes |
| Arm B Placebo/QHPV | CD4 Percent Over Time | CD4 percent at week 104 | 36 percentage of total lymphocytes |
| Arm B Placebo/QHPV | CD4 Percent Over Time | CD4 percent at week 108 | 34 percentage of total lymphocytes |
| Arm B Placebo/QHPV | CD4 Percent Over Time | CD4 percent at week 120 | 37 percentage of total lymphocytes |
| Arm B Placebo/QHPV | CD4 Percent Over Time | CD4 percent at week 124 | 35 percentage of total lymphocytes |
| Arm B Placebo/QHPV | CD4 Percent Over Time | CD4 percent at study entry | 36 percentage of total lymphocytes |
| Arm B Placebo/QHPV | CD4 Percent Over Time | CD4 percent at week 8 | 36 percentage of total lymphocytes |
| Arm B Placebo/QHPV | CD4 Percent Over Time | CD4 percent at week 12 | 37 percentage of total lymphocytes |
| Arm B Placebo/QHPV | CD4 Percent Over Time | CD4 percent at week 24 | 35 percentage of total lymphocytes |
| Arm B Placebo/QHPV | CD4 Percent Over Time | CD4 percent at week 28 | 34 percentage of total lymphocytes |
| Arm B Placebo/QHPV | CD4 Percent Over Time | CD4 percent at week 72 | 34 percentage of total lymphocytes |
| Arm B Placebo/QHPV | CD4 Percent Over Time | CD4 percent at week 96 | 34 percentage of total lymphocytes |
| Arm B Placebo/QHPV | CD4 Percent Over Time | CD4 percent at week 100 | 35 percentage of total lymphocytes |
Secondary
HIV-1 Viral Load (Ribonucleic Acid [RNA] Copies/ml) Over Time
Time frame: Arm A week 0, 8, 12, 24, 28, 72, 96, 100 and 108; Arm B week 0, 8, 12, 24, 28, 72, 96, 100, 104, 108, 120, and 124.
Population: Any participant who received at least one study vaccine/placebo and with non-missing HIV-1 viral load at the respective time point.
| Arm | Measure | Group | Value (LOG_MEAN) |
|---|---|---|---|
| Arm A QHPV | HIV-1 Viral Load (Ribonucleic Acid [RNA] Copies/ml) Over Time | Log10(RNA) at week 72 | 2.7 Log10 (copies/mL) |
| Arm A QHPV | HIV-1 Viral Load (Ribonucleic Acid [RNA] Copies/ml) Over Time | Log10(RNA) at study entry | 2.7 Log10 (copies/mL) |
| Arm A QHPV | HIV-1 Viral Load (Ribonucleic Acid [RNA] Copies/ml) Over Time | Log10(RNA) at week 96 | 2.6 Log10 (copies/mL) |
| Arm A QHPV | HIV-1 Viral Load (Ribonucleic Acid [RNA] Copies/ml) Over Time | Log10(RNA) at week 24 | 2.8 Log10 (copies/mL) |
| Arm A QHPV | HIV-1 Viral Load (Ribonucleic Acid [RNA] Copies/ml) Over Time | Log10(RNA) at week 100 | 2.6 Log10 (copies/mL) |
| Arm A QHPV | HIV-1 Viral Load (Ribonucleic Acid [RNA] Copies/ml) Over Time | Log10(RNA) at week 108 | 2.6 Log10 (copies/mL) |
| Arm A QHPV | HIV-1 Viral Load (Ribonucleic Acid [RNA] Copies/ml) Over Time | Log10(RNA) at week 8 | 2.8 Log10 (copies/mL) |
| Arm A QHPV | HIV-1 Viral Load (Ribonucleic Acid [RNA] Copies/ml) Over Time | Log10(RNA) at week 28 | 2.7 Log10 (copies/mL) |
| Arm A QHPV | HIV-1 Viral Load (Ribonucleic Acid [RNA] Copies/ml) Over Time | Log10(RNA) at week 12 | 2.7 Log10 (copies/mL) |
| Arm B Placebo/QHPV | HIV-1 Viral Load (Ribonucleic Acid [RNA] Copies/ml) Over Time | Log10(RNA) at week 108 | 2.5 Log10 (copies/mL) |
| Arm B Placebo/QHPV | HIV-1 Viral Load (Ribonucleic Acid [RNA] Copies/ml) Over Time | Log10(RNA) at week 120 | 2.3 Log10 (copies/mL) |
| Arm B Placebo/QHPV | HIV-1 Viral Load (Ribonucleic Acid [RNA] Copies/ml) Over Time | Log10(RNA) at study entry | 2.6 Log10 (copies/mL) |
| Arm B Placebo/QHPV | HIV-1 Viral Load (Ribonucleic Acid [RNA] Copies/ml) Over Time | Log10(RNA) at week 124 | 2.3 Log10 (copies/mL) |
| Arm B Placebo/QHPV | HIV-1 Viral Load (Ribonucleic Acid [RNA] Copies/ml) Over Time | Log10(RNA) at week 100 | 2.4 Log10 (copies/mL) |
| Arm B Placebo/QHPV | HIV-1 Viral Load (Ribonucleic Acid [RNA] Copies/ml) Over Time | Log10(RNA) at week 104 | 2.4 Log10 (copies/mL) |
| Arm B Placebo/QHPV | HIV-1 Viral Load (Ribonucleic Acid [RNA] Copies/ml) Over Time | Log10(RNA) at week 8 | 2.8 Log10 (copies/mL) |
| Arm B Placebo/QHPV | HIV-1 Viral Load (Ribonucleic Acid [RNA] Copies/ml) Over Time | Log10(RNA) at week 12 | 2.8 Log10 (copies/mL) |
| Arm B Placebo/QHPV | HIV-1 Viral Load (Ribonucleic Acid [RNA] Copies/ml) Over Time | Log10(RNA) at week 24 | 2.7 Log10 (copies/mL) |
| Arm B Placebo/QHPV | HIV-1 Viral Load (Ribonucleic Acid [RNA] Copies/ml) Over Time | Log10(RNA) at week 28 | 2.8 Log10 (copies/mL) |
| Arm B Placebo/QHPV | HIV-1 Viral Load (Ribonucleic Acid [RNA] Copies/ml) Over Time | Log10(RNA) at week 72 | 2.7 Log10 (copies/mL) |
| Arm B Placebo/QHPV | HIV-1 Viral Load (Ribonucleic Acid [RNA] Copies/ml) Over Time | Log10(RNA) at week 96 | 2.4 Log10 (copies/mL) |