Primary and Booster Vaccination Study With a Pneumococcal Vaccine in HIV Infected, HIV Exposed Uninfected and HIV Uninfected Children 6 to 10 Weeks of Age.

Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes.

Concentrations were given in microgram per millilitre (µg/mL) and were expressed in geometric mean antibody concentrations. Pneumococcal vaccine serotypes assessed were 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Data were collected post-Dose 3 at Month 3 and post-Dose 4 at Month 9 for the HIV+/+, HIV+/- and HIV- (3+1) groups, post-Dose 3 at Month 3 and at Month 9 for HIV- (3+0) group, and post-Dose 2 at Month 3 and post-Dose 3 at Month 9 for the HIV- (2+1) Group. The cut-off of the assay is 0.05 µg/mL.

Time frame: At Month 3 and Month 9

Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes.

Concentrations were given in microgram per millilitre (µg/mL) and were expressed in geometric mean antibody concentrations. Pneumococcal vaccine serotypes assessed were 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Data were collected post-Dose 4 at Month 23 for the HIV+/+, HIV+/- and HIV- (3+1) groups and post-Dose 3 at Month 23 for HIV- (3+0) and HIV- (2+1) groups. The cut-off of the assay is 0.05 µg/mL.

Time frame: up to study end at Month 23 (24-27 months of age)

Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes.

Pneumococcal vaccine serotypes assessed were 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Data were collected post-Dose 3 at Month 3 and post-Dose 4 at Month 9 for the HIV+/+, HIV+/- and HIV- (3+1) groups,post-Dose 3 at Month 3 and at Month 9 for HIV- (3+0) group, and post-Dose 2 at Month 3 and post-Dose 3 at Month 9 for the HIV- (2+1) Group. Streptococcus pneumoniae opsonophagocytic activity was measured by a killing-assay using a HL 60 cell line. The results are presented as the dilution of serum (opsonic titer) able to sustain 50% killing of live pneumococci under the assay conditions. The cut-off of the assay is an opsonic titer of 8.

Time frame: At Month 3 and at Month 9

Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes.

Pneumococcal vaccine serotypes assessed were 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Data were collected post-Dose 4 at Month 23 for the HIV+/+, HIV+/- and HIV- (3+1) groups and post-Dose 3 at Month 23 for HIV- (3+0) and HIV- (2+1) groups. Streptococcus pneumoniae opsonophagocytic activity was measured by a killing-assay using a HL 60 cell line. The results are presented as the dilution of serum (opsonic titer) able to sustain 50% killing of live pneumococci under the assay conditions. The cut-off of the assay is an opsonic titer of 8.

Time frame: up to study end at Month 23 (24-27 months of age)

Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A.

Concentrations were given in microgram per millilitre (µg/mL) and were expressed in geometric mean antibody concentrations. Cross-reactive pneumococcal vaccine serotypes assessed were 6A and 19A. Data were collected post-Dose 3 at Month 3 and post-Dose 4 at Month 9 for the HIV+/+, HIV+/- and HIV- (3+1) groups,post-Dose 3 at Month 3 and at Month 9 for HIV- (3+0) group, and post-Dose 2 at Month 3 and post-Dose 3 at Month 9 for the HIV- (2+1) Group. The cut-off of the assay is 0.05 µg/mL.

Time frame: At Month 3 and Month 9

Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A.

Concentrations were given in microgram per millilitre (µg/mL) and were expressed in geometric mean antibody concentrations. Cross-reactive pneumococcal vaccine serotypes assessed were 6A and 19A. Data were collected post-Dose 4 at Month 23 for the HIV+/+, HIV+/- and HIV- (3+1) groups and post-Dose 3 at Month 23 for HIV- (3+0) and HIV- (2+1) groups. The cut-off of the assay is 0.05 µg/mL.

Time frame: up to study end at Month 23 (24-27 months of age)

Opsonophagocytic Titers Against Cross-reactive Pneumococcal Serotypes 6A and 19A.

Cross-reactive pneumococcal vaccine serotypes assessed were 6A and 19A. Data were collected post-Dose 3 at Month 3 and post-Dose 4 at Month 9 for the HIV+/+, HIV+/- and HIV- (3+1) groups,post-Dose 3 at Month 3 and at Month 9 for HIV- (3+0) group, and post-Dose 2 at Month 3 and post-Dose 3 at Month 9 for the HIV- (2+1) Group. Streptococcus pneumoniae opsonophagocytic activity was measured by a killing-assay using a HL 60 cell line. The results are presented as the dilution of serum (opsonic titer) able to sustain 50% killing of live pneumococci under the assay conditions. The cut-off of the assay is an opsonic titer of 8.

Time frame: At Month 3 and at Month 9

Opsonophagocytic Titers Against Cross-reactive Pneumococcal Serotypes 6A and 19A.

Cross-reactive pneumococcal vaccine serotypes assessed were 6A and 19A. Data were collected post-Dose 4 at Month 23 for the HIV+/+, HIV+/- and HIV- (3+1) groups and post-Dose 3 at Month 23 for HIV- (3+0) and HIV- (2+1) groups. Streptococcus pneumoniae opsonophagocytic activity was measured by a killing-assay using a HL 60 cell line. The results are presented as the dilution of serum (opsonic titer) able to sustain 50% killing of live pneumococci under the assay conditions. The cut-off of the assay is an opsonic titer of 8.

Time frame: up to study end at Month 23 (24-27 months of age)

Concentrations of Antibodies Against Protein D (PD) by ELISA

Concentrations of antibodies are presented as GMCs expressed as ELISA units per milliliter (EL.U/mL). The cut-off of the assay was 100 EL.U/mL. Data were collected post-Dose 3 at Month 3 and post-Dose 4 at Month 9 for the HIV+/+, HIV+/- and HIV- (3+1) groups,post-Dose 3 at Month 3 and at Month 9 for HIV- (3+0) group, and post-Dose 2 at Month 3 and post-Dose 3 at Month 9 for the HIV- (2+1) Group.

Time frame: At Month 3 and at Month 9

Concentrations of Antibodies Against Protein D (PD) by ELISA.

Concentrations of antibodies are presented as GMCs expressed as ELISA units per milliliter (EL.U/mL). The cut-off of the assay was 100 EL.U/mL. Data were collected post-Dose 4 at Month 23 for the HIV+/+, HIV+/- and HIV- (3+1) groups and post-Dose 3 at Month 23 for HIV- (3+0) and HIV- (2+1) groups.

Time frame: up to study end at Month 23 (24-27 months of age)

Concentrations of Antibodies Against Diphtheria Toxoid (DT) and Tetanus Toxoid (TT).

Concentrations of antibodies are presented as GMCs expressed as International units per millilitre (IU/mL) The cut-off of the assay is 0.1IU/mL.

Time frame: 1 month following primary immunization (at Month 3)

Concentrations of Antibodies Against Diphtheria Toxoid (DT) and Tetanus Toxoid (TT).

Concentrations of antibodies are presented as GMCs expressed as International units per millilitre (IU/mL). The cut-off of the assay is 0.1IU/mL.

Time frame: 1 month after the booster dose of DTPw-HBV/Hib vaccine (at Month 15)

Concentrations of Antibodies Against Bordetella Pertussis (BPT) by ELISA.

Concentrations of antibodies are presented as GMCs expressed as ELISA units per millilitre (EL.U/mL). The cut-off of the assay is 15 EL.U/mL.

Time frame: 1 month following primary immunization (at Month 3)

Concentrations of Antibodies Against Bordetella Pertussis (BPT) by ELISA .

Concentrations of antibodies are presented as GMCs expressed as ELISA units per millilitre (EL.U/mL). The cut-off of the assay is 15 EL.U/mL.

Time frame: 1 month after the booster dose of DTPw-HBV/Hib vaccine (at Month 15)

Concentrations of Antibodies Against Polyribosyl-ribitol Phosphate (PRP)

Concentrations of antibodies are presented as GMCs expressed as microgram per millilitre (µg/mL). The cut-off of the assay is 0.15 µg/mL.

Time frame: 1 month following primary immunization (at Month 3)

Concentrations of Antibodies Against Polyribosyl-ribitol Phosphate (PRP)

Concentrations of antibodies are presented as GMCs expressed as microgram per millilitre (µg/mL). The cut-off of the assay is 0.15 µg/mL.

Time frame: 1 month after the booster vaccination (at Month 15)

Concentrations of Antibodies Against Hepatitis B Surface Antigen (HBs) by ELISA

Concentrations of antibodies are presented as GMCs expressed as milli-International units per milliliter (mIU/mL). The cut-off of the assay is 10 mIU/mL. As a decrease in the specificity of the anti-HBs ELISA assay had been observed in some studies for low levels of antibody (10-100 mIU/mL), the table showed results following partial or complete retesting/reanalysis

Time frame: 1 month following primary immunization (at Month 3)

Concentrations of Antibodies Against Hepatitis B Surface Antigen (HBs) by ELISA.

Concentrations of antibodies were presented as GMCs expressed as milli-International units per milliliter (mIU/mL). The cut-off of the assay was 10 mIU/mL. As a decrease in the specificity of the anti-HBs ELISA assay had been observed in some studies for low levels of antibody (10-100 mIU/mL), the table showed results following partial or complete retesting/reanalysis

Time frame: 1 month after the booster dose of DTPw-HBV/Hib vaccine (at Month 15)

Concentrations of Antibodies Against Rotavirus Immunoglobulin A (Rotavirus IgA), by Rotarix Vaccination Status.

Concentrations of antibodies are presented as GMCs expressed as units per millilitre (U/mL). The cut-off of the assay is 20 U/mL. Data were collected for subjects who received 1, 2 doses or no Rotarix dose during the study.

Time frame: 1 month after the administration of the second vaccine dose (at Month 3)

Concentrations of Antibodies Against Measles

Concentrations of antibodies are presented as GMCs expressed as milli-International units per milliliter (mIU/mL).The cut-off of the assay is 150 mIU/mL.

Time frame: 1 month following administration of the 1st and 2nd vaccine dose (at Months 9 and 15)

Anti-LytC IgA and Anti-PhtD IgA Antibodies Concentrations in Salivary Samples

Salivary antibodies against selected common bacterial protein antigens. Salivary samples (1.0 mL) were collected by using an Oracol™ device consisting of a sponge (2 cm3) placed on a stick that was used to brush the teeth and gums to absorb the saliva. Salivary samples were sent to RMPRU (or GSK Biologicals' designated validated laboratory) where the sponge was centrifuged to extract the saliva and that was immediately stored at -70°C. The cut-off of the assay was 2.3 U/mL for anti-LytC IgA and 2.2 U/mL for anti PhtD IgA.

Time frame: up to study end at Month 23 (24-27 months of age)

Number of Swabs With Positive Cultures of Haemophilus Influenzae and/or Streptococcus Pneumoniae (Vaccine Serotypes, Cross-reactive or Other Serotypes) and Other Bacterial Pathogens in the Nasopharynx.

Positive cultures of H. influenza\* (HI) and S. pneumonia(SP) and other bacterial pathogens such as Moraxella catarrhalis(MC), Group A streptococci and Staphylococcus aureus (SA), identified in the nasopharynx at each swab time point: Month (Mth) 0 (Pre-vaccination time point at 6-12 weeks of age), Mth 3 (18 weeks of age), Mth 8 (9-10 Months of age), Mth 9 (10-11 Months of age), Mth 11 (12-13 Months of age), Mth 14 (15-18 Months of age), Mth 15 (16-19 Months of age) and Mth 23 (24-27 Months of age). \*Data presented included only results from samples confirmed as positive for Hi/Non Typeable Hi after differentiation from H. haemolyticus by Polymerase Chain Reaction (PCR) assay

Time frame: up to study end at Month 23 (24-27 months of age)

Number of Subjects With Acquisition of New Streptococcus Pneumoniae and Haemophilus Influenzae Strains Identified in Nasopharyngeal Swabs

Acquisition of new H. influenza\* (HI) and S. pneumonia(SP) strains, identified in the nasopharynx at each swab time point: Month (Mth) 3 (18 weeks of age), Mth 8 (9-10 Months of age), Mth 9 (10-11 Months of age), Mth 11 (12-13 Months of age), Mth 14 (15-18 Months of age), Mth 15 (16-19 Months of age) and Mth 23 (24-27 Months of age). \*Data presented included only results from samples confirmed as positive for Hi/Non Typeable Hi after differentiation from H. haemolyticus by PCR assay

Time frame: up to study end at Month 23 (24-27 months of age)

Number of Subjects With Any and Severe (Grade 3) Solicited Local Adverse Events (AEs).

Solicited local AEs assessed were pain, redness and swelling. Any = incidence of any local symptom regardless of intensity grade. Grade 3 pain = cried when limb was moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling above 30 millimetre.

Time frame: During the 4-day (Days 0-3) post-primary vaccination period across doses

Number of Subjects With Any, Severe (Grade 3) and Related Solicited General Adverse Events (AEs).

General AEs = diarrhoea, drowsiness, irritability, loss of appetite, vomiting and fever (axillary ≥ 37.5 degrees Celsius). Any= Incidence of any symptom regardless of intensity grade or relationship to vaccination. Grade 3: drowsiness = prevented normal activity. irritability = crying that could not be comforted/ prevented normal activity. loss of appetite = not eating at all. diarrhoea: ≥ 6 looser than normal stools/day. vomiting: ≥ 3 episodes of vomiting/day. Fever = \> 39.5°C Related = symptom assessed by the investigator as related to the vaccination.

Time frame: During the 4-day (Days 0-3) post-primary vaccination period across doses

Number of Subjects With Any and Severe (Grade 3) Solicited Local Adverse Events (AEs).

Solicited local AEs assessed were pain, redness and swelling. Any = incidence of any local symptom regardless of intensity grade. Grade 3 pain = cried when limb was moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling above 30 millimetre.

Time frame: During the 4-day (Days 0-3) period following booster vaccination with Synflorix vaccine

Number of Subjects With Any, Severe (Grade 3) and Related Solicited General Adverse Events (AEs).

Solicited general AEs = drowsiness, irritability, loss of appetite and fever (axillary ≥ 37.5 degrees Celsius). Any= Incidence of any symptom regardless of intensity grade or relationship to vaccination. Grade 3: drowsiness = prevented normal activity. irritability = crying that could not be comforted/ prevented normal activity. loss of appetite = not eating at all. Fever = temperature \> 39.5°C Related = symptom assessed by the investigator as related to the vaccination.

Time frame: During the 4-day (Days 0-3) period following booster vaccination with Synflorix vaccine

Number of Subjects With Unsolicited AEs.

An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) 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.

Time frame: Within the 31-day (Days 0-30) post-primary vaccination period

Number of Subjects With Unsolicited AEs.

An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) 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.

Time frame: Within the 31-day (Days 0-30) post Synflorix booster vaccination period

Number of Subjects With Serious Adverse Events (SAEs).

SAEs assessed include medical occurrences that results in death, are life threatening, require hospitalization or prolongation of hospitalization, results in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subjects.

Time frame: From study start at Month 0 (6 weeks of age and above) up to study end at Month 23 (24-27 months of age)