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.

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The oral poliovirus vaccine could be given at any time during the study (routinely given concurrently with Tritanrix™-HepB/Hib vaccine) but was not considered as study vaccine.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
The study included 3 populations defined based on the human immunodeficiency virus status of the mother and the infant. Infant born from: a HIV positive mother and HIV infected at Month 0 = HIV+/+. a HIV positive mother and HIV exposed uninfected at screening = HIV+/-. a HIV negative mother and HIV unexposed uninfected at Month 0 = HIV-

Reporting Groups

	Description
HIV+/+ Group	Infants born from a HIV positive mother and confirmed as HIV infected. Subjects received 3 primary doses (at 6, 10 & 14 weeks of age, at study Months 0, 1 and 2) and 1 booster dose of Synflorix™ vaccine (at 9 months of age, at study Month 8). Subjects in the group also received 3 primary vaccine doses (at 6, 10 & 14 weeks of age, at study Months 0, 1 and 2) and 1 booster vaccine dose (at 15-18 months of age, at study Month 14) of Tritanrix™-HepB/Hib, 2 vaccine doses of Rotarix™ (at 10 & 14 weeks of age, at study Months 1 and 2), and 2 doses of measles vaccine (9-10 months of age & 15-18 months of age, at study Months 8 and 14). Measles vaccine was not considered as a study vaccine. The Synflorix™ vaccine was administered intramuscularly in the right thigh, the Tritanrix™-HepB/Hib vaccine was administered IM in the left anterolateral thigh during the primary vaccination and in the left anterolateral thigh or left deltoid region during booster vaccination. Rotarix™ was given orally.
HIV+/- Group	Infants born from a HIV positive mother and confirmed as HIV exposed uninfected. Subjects received 3 primary doses (at 6, 10 & 14 weeks of age, at study Months 0, 1 and 2) and 1 booster dose of Synflorix™ vaccine (at 9 months of age, at study Month 8). Subjects in the group also received 3 primary vaccine doses (at 6, 10 & 14 weeks of age, at study Months 0, 1 and 2) and 1 booster vaccine dose (at 15-18 months of age, at study Month 14) of Tritanrix™-HepB/Hib, 2 vaccine doses of Rotarix™ (at 10 & 14 weeks of age, at study Months 1 and 2), and 2 doses of measles vaccine (9-10 months of age & 15-18 months of age, at study Months 8 and 14). Measles vaccine was not considered as a study vaccine. The Synflorix™ vaccine was administered IM in the right thigh, the Tritanrix™-HepB/Hib vaccine was administered IM in the left anterolateral thigh during the primary vaccination and in the left anterolateral thigh or left deltoid region during booster vaccination. Rotarix™ was given orally.
HIV- (3+1) Group	Infants born from a HIV negative mother and confirmed as HIV unexposed uninfected. Subjects received 3 primary doses (at 6, 10 & 14 weeks of age, at study Months 0, 1 and 2) and 1 booster dose of Synflorix™ vaccine (at 9 months of age, at study Month 8). Subjects in the group also received 3 primary vaccine doses (at 6, 10 & 14 weeks of age, at study Months 0, 1 and 2) and 1 booster vaccine dose (at 15-18 months of age, at study Month 14) of Tritanrix™-HepB/Hib, 2 vaccine doses of Rotarix™ (at 10 & 14 weeks of age, at study Months 1 and 2), and 2 doses of measles vaccine (9-10 months of age & 15-18 months of age, at study Months 8 and 14). Measles vaccine was not considered as a study vaccine. The Synflorix™ vaccine was administered IM in the right thigh, the Tritanrix™-HepB/Hib vaccine was administered IM in the left anterolateral thigh during the primary vaccination and in the left anterolateral thigh or left deltoid region during booster vaccination. Rotarix™ was given orally.
HIV- (EPI) Group	Infants born from a HIV negative mother and confirmed as HIV unexposed uninfected.Subjects received 3 primary doses of Synflorix™ vaccine (at 6, 10 & 14 weeks of age, at study Months 0, 1 and 2). Subjects in the group also received 3 primary vaccine doses (at 6, 10 & 14 weeks of age, at study Months 0, 1 and 2) and 1 booster vaccine dose (at 15-18 months of age, at study Month 14) of Tritanrix™-HepB/Hib, 2 vaccine doses of Rotarix™ (at 10 & 14 weeks of age, at study Months 1 and 2), and 2 doses of measles vaccine (9-10 months of age & 15-18 months of age, at study Months 8 and 14). Measles vaccine was not considered as a study vaccine. The Synflorix™ vaccine was administered IM in the right thigh, the Tritanrix™-HepB/Hib vaccine was administered IM in the left anterolateral thigh during the primary vaccination and in the left anterolateral thigh or left deltoid region during booster vaccination. Rotarix™ was given orally.
HIV- (2+1) Group	Infants born from a HIV negative mother and confirmed as HIV unexposed uninfected.Subjects received 2 primary doses (at 6 & 14 weeks of age at study Months 0 and 2) and 1 booster dose of Synflorix™ vaccine (at 9 months of age, at study Month 8). Subjects in the group also received 3 primary vaccine doses (at 6, 10 & 14 weeks of age, at study Months 0, 1 and 2) and 1 booster vaccine dose (at 15-18 months of age, at study Month 14) of Tritanrix™-HepB/Hib, 2 vaccine doses of Rotarix™ (at 10 & 14 weeks of age, at study Months 1 and 2), and 2 doses of measles vaccine (9-10 months of age & 15-18 months of age, at study Months 8 and 14). Measles vaccine was not considered as a study vaccine. The Synflorix™ vaccine was administered IM in the right thigh, the Tritanrix™-HepB/Hib vaccine was administered IM in the left anterolateral thigh during the primary vaccination and in the left anterolateral thigh or left deltoid region during booster vaccination. Rotarix™ was given orally.

Participant Flow:   Overall Study

	HIV+/+ Group	HIV+/- Group	HIV- (3+1) Group	HIV- (EPI) Group	HIV- (2+1) Group
STARTED	87	97	100	100	100
COMPLETED	81	92	98	94	98
NOT COMPLETED	6	5	2	6	2
Adverse Event	6	3	0	3	0
Withdrawal by Subject	0	0	1	0	2
Lost to Follow-up	0	1	1	3	0
Unspecified	0	1	0	0	0

Reporting Groups

	Description
HIV+/+ Group	Infants born from a HIV positive mother and confirmed as HIV infected. Subjects received 3 primary doses (at 6, 10 & 14 weeks of age, at study Months 0, 1 and 2) and 1 booster dose of Synflorix™ vaccine (at 9 months of age, at study Month 8). Subjects in the group also received 3 primary vaccine doses (at 6, 10 & 14 weeks of age, at study Months 0, 1 and 2) and 1 booster vaccine dose (at 15-18 months of age, at study Month 14) of Tritanrix™-HepB/Hib, 2 vaccine doses of Rotarix™ (at 10 & 14 weeks of age, at study Months 1 and 2), and 2 doses of measles vaccine (9-10 months of age & 15-18 months of age, at study Months 8 and 14). Measles vaccine was not considered as a study vaccine. The Synflorix™ vaccine was administered intramuscularly in the right thigh, the Tritanrix™-HepB/Hib vaccine was administered IM in the left anterolateral thigh during the primary vaccination and in the left anterolateral thigh or left deltoid region during booster vaccination. Rotarix™ was given orally.
HIV+/- Group	Infants born from a HIV positive mother and confirmed as HIV exposed uninfected. Subjects received 3 primary doses (at 6, 10 & 14 weeks of age, at study Months 0, 1 and 2) and 1 booster dose of Synflorix™ vaccine (at 9 months of age, at study Month 8). Subjects in the group also received 3 primary vaccine doses (at 6, 10 & 14 weeks of age, at study Months 0, 1 and 2) and 1 booster vaccine dose (at 15-18 months of age, at study Month 14) of Tritanrix™-HepB/Hib, 2 vaccine doses of Rotarix™ (at 10 & 14 weeks of age, at study Months 1 and 2), and 2 doses of measles vaccine (9-10 months of age & 15-18 months of age, at study Months 8 and 14). Measles vaccine was not considered as a study vaccine. The Synflorix™ vaccine was administered IM in the right thigh, the Tritanrix™-HepB/Hib vaccine was administered IM in the left anterolateral thigh during the primary vaccination and in the left anterolateral thigh or left deltoid region during booster vaccination. Rotarix™ was given orally.
HIV- (3+1) Group	Infants born from a HIV negative mother and confirmed as HIV unexposed uninfected. Subjects received 3 primary doses (at 6, 10 & 14 weeks of age, at study Months 0, 1 and 2) and 1 booster dose of Synflorix™ vaccine (at 9 months of age, at study Month 8). Subjects in the group also received 3 primary vaccine doses (at 6, 10 & 14 weeks of age, at study Months 0, 1 and 2) and 1 booster vaccine dose (at 15-18 months of age, at study Month 14) of Tritanrix™-HepB/Hib, 2 vaccine doses of Rotarix™ (at 10 & 14 weeks of age, at study Months 1 and 2), and 2 doses of measles vaccine (9-10 months of age & 15-18 months of age, at study Months 8 and 14). Measles vaccine was not considered as a study vaccine. The Synflorix™ vaccine was administered IM in the right thigh, the Tritanrix™-HepB/Hib vaccine was administered IM in the left anterolateral thigh during the primary vaccination and in the left anterolateral thigh or left deltoid region during booster vaccination. Rotarix™ was given orally.
HIV- (EPI) Group	Infants born from a HIV negative mother and confirmed as HIV unexposed uninfected.Subjects received 3 primary doses of Synflorix™ vaccine (at 6, 10 & 14 weeks of age, at study Months 0, 1 and 2). Subjects in the group also received 3 primary vaccine doses (at 6, 10 & 14 weeks of age, at study Months 0, 1 and 2) and 1 booster vaccine dose (at 15-18 months of age, at study Month 14) of Tritanrix™-HepB/Hib, 2 vaccine doses of Rotarix™ (at 10 & 14 weeks of age, at study Months 1 and 2), and 2 doses of measles vaccine (9-10 months of age & 15-18 months of age, at study Months 8 and 14). Measles vaccine was not considered as a study vaccine. The Synflorix™ vaccine was administered IM in the right thigh, the Tritanrix™-HepB/Hib vaccine was administered IM in the left anterolateral thigh during the primary vaccination and in the left anterolateral thigh or left deltoid region during booster vaccination. Rotarix™ was given orally.
HIV- (2+1) Group	Infants born from a HIV negative mother and confirmed as HIV unexposed uninfected.Subjects received 2 primary doses (at 6 & 14 weeks of age at study Months 0 and 2) and 1 booster dose of Synflorix™ vaccine (at 9 months of age, at study Month 8). Subjects in the group also received 3 primary vaccine doses (at 6, 10 & 14 weeks of age, at study Months 0, 1 and 2) and 1 booster vaccine dose (at 15-18 months of age, at study Month 14) of Tritanrix™-HepB/Hib, 2 vaccine doses of Rotarix™ (at 10 & 14 weeks of age, at study Months 1 and 2), and 2 doses of measles vaccine (9-10 months of age & 15-18 months of age, at study Months 8 and 14). Measles vaccine was not considered as a study vaccine. The Synflorix™ vaccine was administered IM in the right thigh, the Tritanrix™-HepB/Hib vaccine was administered IM in the left anterolateral thigh during the primary vaccination and in the left anterolateral thigh or left deltoid region during booster vaccination. Rotarix™ was given orally.
Total	Total of all reporting groups

Baseline Measures

	HIV+/+ Group	HIV+/- Group	HIV- (3+1) Group	HIV- (EPI) Group	HIV- (2+1) Group	Total
Number of Participants   [units: participants]	87	97	100	100	100	484
Age   [units: Weeks] Mean ± Standard Deviation	6.6  ± 0.92	6.3  ± 0.64	6.1  ± 0.41	6.1  ± 0.35	6.1  ± 0.29	6.2  ± 0.52
Gender   [units: Subjects]
Female	50	46	58	50	47	251
Male	37	51	42	50	53	233

1.  Primary:

Number of Subjects With Anti-pneumococcal Vaccine Serotype Antibody Concentrations Equal to or Above 0.20 Microgram Per Millilitre (µg/mL).   [ Time Frame: 1 month following primary immunization (post-Dose 3 at Month 3 for the HIV+/+ Group, HIV+/- Group, HIV- (3+1) Group, HIV- (EPI) Group and post-Dose 2 at Month 3 for the HIV- (2+1) Group) ]

2.  Secondary:

Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes.   [ Time Frame: 1 month following primary immunization (at Month 3) and 1 month after the booster vaccination (at Month 9) ]

3.  Secondary:

Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes.   [ Time Frame: 1 month following primary immunization (at Month 3) and 1 month after the booster vaccination (at Month 9) ]

4.  Secondary:

Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A.   [ Time Frame: 1 month following primary immunization (at Month 3) and 1 month after the booster vaccination (at Month 9) ]

5.  Secondary:

Opsonophagocytic Titers Against Cross-reactive Pneumococcal Serotypes 6A and 19A.   [ Time Frame: 1 month following primary immunization (at Month 3) and 1 month after the booster vaccination (at Month 9) ]

6.  Secondary:

Concentrations of Antibodies Against Protein D (PD).   [ Time Frame: 1 month following primary immunization (at Month 3) and 1 month after the booster vaccination (at Month 9) ]

7.  Secondary:

Concentrations of Antibodies Against Diphtheria Toxoid (DT) and Tetanus Toxoid (TT).   [ Time Frame: 1 month following primary immunization (at Month 3) ]

8.  Secondary:

Concentrations of Antibodies Against Bordetella Pertussis.   [ Time Frame: 1 month following primary immunization (at Month 3) ]

9.  Secondary:

Concentrations of Antibodies Against Polyribosyl-ribitol Phosphate (PRP)   [ Time Frame: 1 month following primary immunization (at Month 3) ]

10.  Secondary:

Concentrations of Antibodies Against Hepatitis B Surface Antigen (HBs)   [ Time Frame: 1 month following primary immunization (at Month 3) ]

11.  Secondary:

Concentrations of Antibodies Against Rotavirus Immunoglobulin A (Rotavirus IgA), by Rotarix Vaccination Status.   [ Time Frame: 1 month after the administration of the second vaccine dose (at Month 3) ]

12.  Secondary:

Number of Subjects With Any and Severe (Grade 3) Solicited Local Adverse Events (AEs).   [ Time Frame: During the 4-day (Days 0-3) post-primary vaccination period ]

13.  Secondary:

Number of Subjects With Any, Severe (Grade 3) and Related Solicited General Adverse Events (AEs).   [ Time Frame: During the 4-day (Days 0-3) post-primary vaccination period ]

14.  Secondary:

Number of Subjects With Any and Severe (Grade 3) Solicited Local Adverse Events (AEs).   [ Time Frame: During the 4-day (Days 0-3) period following booster vaccination with Synflorix vaccine ]

15.  Secondary:

Number of Subjects With Any, Severe (Grade 3) and Related Solicited General Adverse Events (AEs).   [ Time Frame: During the 4-day (Days 0-3) period following booster vaccination with Synflorix vaccine ]

16.  Secondary:

Number of Subjects With Unsolicited AEs.   [ Time Frame: Within the 31-day (Days 0-30) post-primary vaccination period ]

17.  Secondary:

Number of Subjects With Unsolicited AEs.   [ Time Frame: Within the 31-day (Days 0-30) post Synflorix booster vaccination period ]

18.  Secondary:

Number of Subjects With Serious Adverse Events (SAEs).   [ Time Frame: From study start (at Month 0) up to 1 month after Synflorix booster vaccination (up to Month 9) ]

19.  Secondary:

Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes.   [ Time Frame: up to study end at Month 23 (24-27 months of age) ]

20.  Secondary:

Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes.   [ Time Frame: up to study end at Month 23 (24-27 months of age) ]

21.  Secondary:

Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A.   [ Time Frame: up to study end at Month 23 (24-27 months of age) ]

22.  Secondary:

Opsonophagocytic Titers Against Cross-reactive Pneumococcal Serotypes 6A and 19A.   [ Time Frame: up to study end at Month 23 (24-27 months of age) ]

23.  Secondary:

Concentrations of Antibodies Against Protein D (PD).   [ Time Frame: up to study end at Month 23 (24-27 months of age) ]

24.  Secondary:

Concentrations of Antibodies Against Diphtheria Toxoid (DT) and Tetanus Toxoid (TT).   [ Time Frame: 1 month after the booster vaccination (at Month 9) ]

25.  Secondary:

Concentrations of Antibodies Against Bordetella Pertussis.   [ Time Frame: 1 month after the booster vaccination (at Month 9) ]

26.  Secondary:

Concentrations of Antibodies Against Polyribosyl-ribitol Phosphate (PRP)   [ Time Frame: 1 month after the booster vaccination (at Month 9) ]

27.  Secondary:

Concentrations of Antibodies Against Hepatitis B Surface Antigen (HBs)   [ Time Frame: 1 month after the booster vaccination (at Month 9) ]

28.  Secondary:

Titers of Antibodies Against Measles   [ Time Frame: 1 month following administration of the 1st and 2nd vaccine dose (at Months 9 and 15) ]

29.  Secondary:

Salivary Antibodies Against Selected Common Bacterial Protein Antigens.   [ Time Frame: up to study end at Month 23 (24-27 months of age) ]

30.  Secondary:

Prevalence of Haemophilus Influenzae and/or Streptococcus Pneumoniae (Vaccine Serotypes, Cross-reactive or Other Serotypes) and Other Bacterial Pathogens in the Nasopharynx.   [ Time Frame: up to study end at Month 23 (24-27 months of age) ]

31.  Secondary:

Acquisition of New S. Pneumoniae and/or H. Influenzae Strains.   [ Time Frame: up to study end at Month 23 (24-27 months of age) ]

32.  Secondary:

Number of Subjects With Serious Adverse Events (SAEs).   [ 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) ]