Number of Human Immunodeficiency Virus Positive Subjects (HIV+) With Any and Grade 3 Solicited Local Symptoms
Assessed solicited local symptoms were pain, redness, swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = significant pain at rest, pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling with a maximum diameter greater than 50 millimeters (mm).
Number of HIV+ Subjects With Any, Grade 3 and Related Solicited General Symptoms
Assessed solicited general symptoms were arthralgia, fatigue, gastrointestinal [nausea, vomiting, diarrhoea and/or abdominal pain], headache, myalgia, rash, temperature [defined as axillary temperature higher than (>) 37.5 degrees Celsius (°C)] and urticaria. Any = occurrence of the symptom regardless of intensity grade and relationship. Grade 3 symptom = symptom that prevented normal activity. Grade 3 temperature = temperature > 39.0 °C. Grade 3 urticaria = urticaria distributed on at least 4 body areas. Related = symptom assessed by the investigator as related to the vaccination.
Number of HIV+ Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs)
An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 symptom = symptom that prevented normal activity. Related = symptom assessed by the investigator as related to the vaccination.
Number of HIV+ Subjects With Serious Adverse Events (SAEs)
SAEs assessed include any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity or represented a congenital anomaly/birth defect in the offspring of a study subject.
Number of HIV+ Subjects With Medically Significant Conditions (MSCs)
Medically significant conditions (MSCs) are defined as AEs prompting emergency room or physician visits that were not related to common diseases, or not related to routine visits for physical examination or vaccination, SAEs that were not related to common diseases.
Number of HIV+ Subjects With Potential Immune-mediated Diseases (pIMDs)
Potential immune-mediated diseases are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology.
Number of HIV+ Subjects Reporting Pregnancies and Outcomes of Reported Pregnancies
Pregnancy related outcomes were: live infant no apparent congenital anomaly, live infant congenital anomaly, elective termination (termin.) no apparent congenital anomaly, elective termination (termin.) congenital anomaly, ectopic pregnancy, spontaneous abortion no apparent congenital (congen.) anomaly, stillbirth no apparent congenital anomaly, stillbirth congenital anomaly, lost to follow-up, pregnancy ongoing, missing.
Number of HIV+ Subjects With Haematological and Biochemical Parameter Abnormalities
Among assessed haematological and biochemical parameters were: alanine aminotransferase [ALAT], basophilis [BSPH], creatinine [CRT], eosinophils [ESPH], haematocrit [HTCR], haemoglobin [HGB], lymphocytes [LYMP], monocytes [MONO], neutrophils [NTPH], platelets [PLAT], red blood cells [RBC] and white blood cells [WBC]. Unknown = value unknown for the specified visit and laboratory parameter; Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.
Cluster of Differentiation 4 (CD4+) Cell Count in HIV+ Subjects at Month 7
CD4+ cell count, expressed in cells/cubic millimeter (mm3), was assessed for HIV+ subjects.
HIV Viral Load (VL) in HIV+ Subjects at Month 7
HIV VL, expressed in HIV copies/milliliter (mL), was assessed for HIV+ subjects.
Number of HIV+ Subjects by World Health Organization (WHO) HIV Clinical Staging
HIV+ subjects were categorised into clinical stages 1 through 4, as per the WHO classification [WHO, 2009].
Pseudovirion-Based Neutralization Assay (PBNA) Titers of Anti-HPV-16/18 Antibodies in HIV+ Subjects, Based on Adapted According-to-protocol (ATP) Cohort for Immunogenicity
Titers of anti-HPV-16/18 antibodies, expressed as Geometric Mean Titers (GMTs), with cut-offs greater than or equal to (≥) 40 estimated dose giving 50% signal reduction when compared to a control without serum (ED50), as assessed by the Pseudovirion-Based Neutralization Assay [PBNA], in HIV+ subjects.
Between-group comparisons to assess non-inferiority were performed on the ATP cohort for immunogenicity (by PBNA, regardless of HPV serostatus at baseline).
Pseudovirion-Based Neutralization Assay (PBNA) Titers of Anti-HPV-16/18 Antibodies in HIV+ Subjects, Based on Total Vaccinated Cohort (TVC)
Titers of anti-HPV-16/18 antibodies, expressed as Geometric Mean Titers (GMTs), with cut-offs greater than or equal to (≥) 40 estimated dose giving 50% signal reduction when compared to a control without serum (ED50), as assessed by the Pseudovirion-Based Neutralization Assay [PBNA], in HIV+ subjects.
Between-group comparisons to assess superiority were performed on the TVC (by PBNA, regardless of HPV serostatus at baseline).
Number of HIV- Subjects With Any and Grade 3 Solicited Local Symptoms
Assessed solicited local symptoms were pain, redness, swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = significant pain at rest, pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling with a maximum diameter greater than 50 millimeters (mm).
Number of HIV- Subjects With Any, Grade 3 and Related Solicited General Symptoms
Assessed solicited general symptoms were arthralgia, fatigue, gastrointestinal [nausea, vomiting, diarrhoea and/or abdominal pain], headache, myalgia, rash, temperature [defined as axillary temperature higher than (>) 37.5 degrees Celsius (°C)] and urticaria. Any = occurrence of the symptom regardless of intensity grade and relationship. Grade 3 symptom = symptom that prevented normal activity. Grade 3 temperature = temperature > 39.0 °C. Grade 3 urticaria = urticaria distributed on at least 4 body areas. Related = symptom assessed by the investigator as related to the vaccination.
Number of HIV- Subjects With Unsolicited Adverse Events (AEs)
An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 symptom = symptom that prevented normal activity. Related = symptom assessed by the investigator as related to the vaccination.
Number of HIV- Subjects With Serious Adverse Events (SAEs)
SAEs assessed include any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity or represented a congenital anomaly/birth defect in the offspring of a study subject.
Number of HIV- Subjects With Medically Significant Conditions (MSCs)
Medically significant conditions (MSCs) are defined as AEs prompting emergency room or physician visits that were not related to common diseases, or not related to routine visits for physical examination or vaccination, SAEs that were not related to common diseases.
Number of HIV- Subjects With Potential Immune-mediated Disease (pIMDs)
Potential immune-mediated diseases are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology.
Number of Subjects Reporting Pregnancies and Outcomes of Reported Pregnancies
Pregnancy related outcomes were: live infant no apparent congenital anomaly, live infant congenital anomaly, elective termination (termin.) no apparent congenital anomaly, elective termination (termin.) congenital anomaly, ectopic pregnancy, spontaneous abortion no apparent congenital (congen.) anomaly, stillbirth no apparent congenital anomaly, stillbirth congenital anomaly, lost to follow-up, pregnancy ongoing, missing.
Number of Subjects With Relevant Abnormalities in Alanine Aminotransferase, Basophils, Creatinine and Eosinophils Parameters
Among assessed haematological and biochemical parameters were: alanine aminotransferase [ALAT], basophils [BSPH], creatinine [CRT], eosinophils [ESPH]. Unknown = value unknown for the specified visit and laboratory parameter; Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.
Number of Subjects With Relevant Abnormalities in Haematocrit, Haemoglobin, Lymphocytes and Monocytes Parameters
Among assessed haematological parameters were: haematocrit [HTCR], haemoglobin [HGB], lymphocytes [LYMP] and monocytes [MONO]. Unknown = value unknown for the specified visit and laboratory parameter; Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.
Number of Subjects With Relevant Abnormalities in Neutrophils, Platelets, Red Blood Cells and White Blood Cells Parameters
Among assessed haematological parameters were: neutrophils [NTPH], platelets [PLAT], red blood cells [RBC] and white blood cells [WBC]. Unknown = value unknown for the specified visit and laboratory parameter; Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.
Number of Subjects With SAEs
SAEs assessed include any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity or represented a congenital anomaly/birth defect in the offspring of a study subject.
Number of Subjects With Medically Significant Conditions (MSCs)
Medically significant conditions (MSCs) are defined as AEs prompting emergency room or physician visits that were not related to common diseases, or not related to routine visits for physical examination or vaccination, SAEs that were not related to common diseases.
Number of Subjects With Potential Immune-mediated Diseases (pIMDs)
Potential immune-mediated diseases are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology.
Cluster of Differentiation 4 (CD4+) Cell Count in HIV+ Subjects at Months 12, 18 and 24
CD4+ cell count, expressed in cells/cubic millimeter (mm3), was assessed for HIV+ subjects.
HIV Viral Load (VL) in HIV+ Subjects at Months 12, 18 and 24
HIV VL, expressed in HIV copies/milliliter (mL), was assessed for HIV+ subjects.
Number of HIV+ Subjects by WHO HIV Clinical Staging
HIV+ subjects were categorised into clinical stages 1 through 4, as per the WHO classification [WHO, 2009].
Pseudovirion-Based Neutralization Assay (PBNA) Titers of Anti-HPV-16/18 Antibodies in HIV- Subjects, Based on TVC
Titers of anti-HPV-16/18 antibodies, expressed as Geometric Mean Titers (GMTs), with cut-offs greater than or equal to (≥) 40 estimated dose giving 50% signal reduction when compared to a control without serum (ED50), as assessed by the Pseudovirion-Based Neutralization Assay [PBNA], for HIV- subjects.
Between-group comparisons to assess superiority were performed on the TVC (by PBNA, regardless of HPV serostatus at baseline).
Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations by Enzyme-linked Immunosorbent Assay (ELISA) in Serum
Anti-HPV-16 and anti-HPV-18 antibody concentrations in serum, are presented as Geometric Mean Concentrations (GMCs), with cut-offs greater than or equal to (≥) 19 ELISA units per milliliter (EU/mL) and 18 EU/mL respectively, as assessed by Enzyme-linked immunosorbent assay (ELISA), in all (HIV+ and HIV-) subjects.
Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations by ELISA in Cervicovaginal Secretion (CVS)
Anti-HPV-16 and anti-HPV-18 antibody concentrations in CVS, are presented as Geometric Mean Concentrations (GMCs), with cut-offs greater than or equal to (≥) 0 EU/mL, as assessed by ELISA, in post-menarcheal subjects who volunteered for this procedure.
Frequency of Specific B-cells for HPV-16/18 Antigens
B-cell memory was assessed by Enzyme Linked Immuno Spot (ELISPOT) assay. The assay was performed in a subset of approximately 100 subjects (50 HIV+ and 50 HIV-).
Frequency of Cluster of Differentiation 4/8 [CD4+/CD8+] T-cell Response
The combinations of cytokines expressed were CD4/8-all doubles, CD4/8-d-cluster of differentiation 40 Ligand (CD40L), CD4/8-d-interferon gamma (IFNG), CD4/8-interleukin-2 (IL-2), CD4/8-d-tumour necrosis alpha (TNFA), as assessed by Intracellular cytokine staining (ICS). The assay was performed in a subset of approximately 100 subjects (50 HIV+ and 50 HIV-).