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Clinical Trial Results:
A phase III, open, controlled study in South Africa to assess the immunogenicity, safety and reactogenicity of GSK Biologicals’ 10-valent pneumococcal conjugate vaccine administered as a 3-dose (6, 10, 14 weeks) primary immunization course in HIV infected infants, HIV exposed uninfected infants and HIV unexposed uninfected infants followed by a booster vaccination at 9-10 months of age.

Summary
EudraCT number	2011-002077-35
Trial protocol	Outside EU/EEA
Global end of trial date	27 Jun 2012

Results information
Results version number	v3(current)
This version publication date	26 Feb 2023
First version publication date	11 Jun 2015
Other versions	v1 , v2
Version creation reason	Correction of full data set Correction of full data set and alignment between registries.

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

111634

ISRCTN number

US NCT number

NCT00829010

WHO universal trial number (UTN)

Sponsor organisation name

GlaxoSmithKline Biologicals

Sponsor organisation address

Rue de l'Institut 89, Rixensart, Belgium, B-1330

Public contact

Clinical Trials Call Center, GlaxoSmithKline Biologicals, 044 2089-904466, GSKClinicalSupportHD@gsk.com

Scientific contact

Clinical Trials Call Center, GlaxoSmithKline Biologicals, 044 2089-904466, GSKClinicalSupportHD@gsk.com

Is trial part of an agreed paediatric investigation plan (PIP)

Yes

EMA paediatric investigation plan number(s)

EMEA-000673-PIP01-09

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Yes

Analysis stage

Final

Date of interim/final analysis

02 Apr 2014

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

27 Jun 2012

Was the trial ended prematurely?

Main objective of the trial

To evaluate and characterize the immune response to the Synflorix vaccine one month following a 3-dose (6, 10 and 14 weeks of age) primary vaccination course in HIV infected infants, HIV exposed uninfected infants and HIV unexposed uninfected infants.

Protection of trial subjects

All subjects were supervised after vaccination with appropriate medical treatment readily available. Vaccines were administered by qualified and trained personnel. Only eligible subjects that had no contraindications to any components of the vaccines were vaccinated. Subjects were followed-up after each vaccination.

Background therapy

Evidence for comparator

Actual start date of recruitment

17 Feb 2009

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

South Africa: 489

Worldwide total number of subjects

489

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

489

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

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. Out of the 489 subjects enrolled in the study, only 484 subjects were assigned to a study group and received vaccination.

Screening details

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-.

Number of subjects started

489

Number of subjects completed

484

Reason: Number of subjects

No study vacccination received: 5

Period 1 title

Overall trial (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

HIV+/+ Group

Arm description

Infants born from a HIV positive mother and confirmed as HIV infected. Subjects received 3 primary doses (at 6, 10 and 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 and 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 and 14 weeks of age, at study Months 1 and 2), and 2 doses of measles vaccine (9-10 months of age and 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 given orally.

Arm type

Experimental

Investigational medicinal product name

Synflorix

Investigational medicinal product code

GSK1024850A

Other name

10Pn-PD-DiT, 10Pn

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

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).

Investigational medicinal product name

Tritanrix-HepB/Hib

Investigational medicinal product code

Other name

DTPW-HBV/Hib, Diphteria toxoid

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

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).

Investigational medicinal product name

Rotarix

Investigational medicinal product code

Other name

HRV

Pharmaceutical forms

Powder and solvent for oral suspension

Routes of administration

Oral use

Dosage and administration details

Subjects received 2 vaccine doses (at 10 & 14 weeks of age, at study Months 1 and 2).

Investigational medicinal product name

Measles

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 2 doses at 9-10 months and 15-18 months of age.

HIV+/- Group

Arm description

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.

Arm type

Experimental

Investigational medicinal product name

Synflorix

Investigational medicinal product code

GSK1024850A

Other name

10Pn-PD-DiT, 10Pn

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

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).

Investigational medicinal product name

Tritanrix-HepB/Hib

Investigational medicinal product code

Other name

DTPW-HBV/Hib

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

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).

Investigational medicinal product name

Rotarix

Investigational medicinal product code

Other name

HRV

Pharmaceutical forms

Powder and solvent for oral suspension

Routes of administration

Oral use

Dosage and administration details

Subjects received 2 vaccine doses (at 10 & 14 weeks of age, at study Months 1 and 2).

Investigational medicinal product name

Measles

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 2 doses at 9-10 months and 15-18 months of age.

HIV-(3+1) Group

Arm description

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.

Arm type

Experimental

Investigational medicinal product name

Synflorix

Investigational medicinal product code

GSK1024850A

Other name

10Pn-PD-DiT, 10Pn

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

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).

Investigational medicinal product name

Tritanrix-HepB/Hib

Investigational medicinal product code

Other name

DTPW-HBV/Hib

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

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).

Investigational medicinal product name

Rotarix

Investigational medicinal product code

Other name

HRV

Pharmaceutical forms

Powder and solvent for oral suspension

Routes of administration

Oral use

Dosage and administration details

Subjects received 2 vaccine doses (at 10 & 14 weeks of age, at study Months 1 and 2).

Investigational medicinal product name

Measles

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 2 doses at 9-10 months and 15-18 months of age.

HIV- (3+0) Group

Arm description

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.

Arm type

Experimental

Investigational medicinal product name

Synflorix

Investigational medicinal product code

GSK1024850A

Other name

10Pn-PD-DiT, 10Pn

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 3 primary doses (at 6, 10 & 14 weeks of age, at study Months 0, 1 and 2).

Investigational medicinal product name

Tritanrix-HepB/Hib

Investigational medicinal product code

Other name

DTPW-HBV/Hib; Diphteria toxoid

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

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).

Investigational medicinal product name

Rotarix

Investigational medicinal product code

Other name

HRV

Pharmaceutical forms

Powder and solvent for oral suspension

Routes of administration

Oral use

Dosage and administration details

Subjects received 2 vaccine doses (at 10 & 14 weeks of age, at study Months 1 and 2).

Investigational medicinal product name

Measles

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 2 doses at 9-10 months and 15-18 months of age.

HIV-(2+1) Group

Arm description

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.

Arm type

Experimental

Investigational medicinal product name

Synflorix

Investigational medicinal product code

GSK1024850A

Other name

10Pn-PD-DiT, 10Pn

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

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).

Investigational medicinal product name

Tritanrix-HepB/Hib

Investigational medicinal product code

Other name

DTPW-HBV/Hib

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

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).

Investigational medicinal product name

Rotarix

Investigational medicinal product code

Other name

HRV

Pharmaceutical forms

Powder and solvent for oral suspension

Routes of administration

Oral use

Dosage and administration details

Subjects received 2 vaccine doses (at 10 & 14 weeks of age, at study Months 1 and 2).

Investigational medicinal product name

Measles

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 2 doses at 9-10 months and 15-18 months of age.

Number of subjects in period 1 ^[1]	HIV+/+ Group	HIV+/- Group	HIV-(3+1) Group	HIV- (3+0) Group	HIV-(2+1) Group
Started	83	101	100	100	100
Completed	73	92	97	92	98
Not completed	10	9	3	8	2
Consent withdrawn by subject	-	1	1	-	2
Adverse event, non-fatal	1	-	-	-	-
Death	5	4	-	3	-
Migrated/moved from study area	3	4	-	5	-
Lost to follow-up	1	-	2	-	-

Notes
[1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: 5 enrolled subjects were not allocated to a group and did not receive a vaccine.

Baseline characteristics

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Reporting group title

HIV+/+ Group

Reporting group description

Reporting group title

HIV+/- Group

Reporting group description

Reporting group title

HIV-(3+1) Group

Reporting group description

Reporting group title

HIV- (3+0) Group

Reporting group description

Reporting group title

HIV-(2+1) Group

Reporting group description

Reporting group values	HIV+/+ Group	HIV+/- Group	HIV-(3+1) Group	HIV- (3+0) Group	HIV-(2+1) Group	Total
Number of subjects	83	101	100	100	100	484
Age categorical
Units: Subjects
In utero	0	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0	0
Infants and toddlers (28 days-23 months)	83	101	100	100	100	484
Children (2-11 years)	0	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0	0
Adults (18-64 years)	0	0	0	0	0	0
From 65-84 years	0	0	0	0	0	0
85 years and over	0	0	0	0	0	0
Age continuous
Units: weeks
arithmetic mean (standard deviation)	6.6 ( 0.92 )	6.3 ( 0.65 )	6.1 ( 0.41 )	6.1 ( 0.35 )	6.1 ( 0.29 )	-
Gender categorical
Units: Subjects
Female	49	47	58	50	47	251
Male	34	54	42	50	53	233

End points

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Reporting group title

HIV+/+ Group

Reporting group description

Reporting group title

HIV+/- Group

Reporting group description

Reporting group title

HIV-(3+1) Group

Reporting group description

Reporting group title

HIV- (3+0) Group

Reporting group description

Reporting group title

HIV-(2+1) Group

Reporting group description

Primary: Number of Subjects With Anti-pneumococcal Vaccine Serotype Antibody Concentrations Equal to or Above 0.20 Microgram Per Millilitre (µg/mL)

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End point title

Number of Subjects With Anti-pneumococcal Vaccine Serotype Antibody Concentrations Equal to or Above 0.20 Microgram Per Millilitre (µg/mL) ^[1]

End point description

Pneumococcal vaccine serotypes assessed were 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. The According-To-Protocol cohort for immunogenicity included evaluable subjects for whom data concerning immunogenicity outcome measures were available. This included subjects for whom assay results were available for antibodies against at least 1 study vaccine antigen component post dose II or III, as applicable, or after booster vaccination.

End point type

Primary

End point timeframe

1 month following primary immunization (post-Dose 3 at Month 3 for the HIV+/+ Group, HIV+/- Group, HIV- (3+1) Group, HIV- (3+0) Group and post-Dose 2 at Month 3 for the HIV- (2+1) Group)

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	HIV+/+ Group	HIV+/- Group	HIV-(3+1) Group	HIV- (3+0) Group	HIV-(2+1) Group
Number of subjects analysed	70	91	93	94	97
Units: Subject
Anti-1 (N=70,91,93,94,97)	69	90	93	94	96
Anti-4 (N=70,91,93,93,97)	69	90	93	93	96
Anti-5 (N=70,91,93,94,97)	70	90	93	94	95
Anti-6B (N=70,91,93,93,97)	61	80	74	83	80
Anti-7F (N=70,91,93,94,97)	69	90	93	94	96
Anti-9V (N=70,91,93,94,97)	68	90	93	94	92
Anti-14 (N=70,91,93,93,97)	69	90	93	93	95
Anti-18C (N=69,91,93,94,97)	69	90	93	94	95
Anti-19F (N=70,91,93,93,96)	68	90	93	93	94
Anti-23F (N=70,91,93,93,97)	63	84	83	84	84

No statistical analyses for this end point

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

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End point title

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

End point description

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 millimeter. The Total Vaccinated cohort included all subjects who received at least one vaccine dose administration, with analysis done solely on subjects for whom post-vaccination results about solicited symptoms were available.

End point type

Secondary

End point timeframe

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

End point values	HIV+/+ Group	HIV+/- Group	HIV-(3+1) Group	HIV- (3+0) Group	HIV-(2+1) Group
Number of subjects analysed	83	101	98	98	98
Units: Subjects
Any pain	73	93	92	95	97
Grade 3 pain	18	18	28	42	34
Any redness	62	80	83	83	84
Redness > 30 mm	14	10	17	20	14
Any swelling	67	83	84	91	84
Swelling > 30 mm	23	32	41	44	31

No statistical analyses for this end point

Secondary: Number of Subjects with Any, Severe (Grade 3) and Related Solicited General Adverse Events (AEs)

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End point title

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

End point description

General AEs = diarrhoea, drowsiness, irritability, loss of appetite, vomiting and fever (axillary greater than or equal to [≥] 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 = greater than (>) 39.5°C Related = symptom assessed by the investigator as related to the vaccination. The Total Vaccinated cohort included all subjects who received at least one vaccine dose administration, with analysis done solely on subjects for whom post-vaccination results about solicited symptoms were available.

End point type

Secondary

End point timeframe

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

End point values	HIV+/+ Group	HIV+/- Group	HIV-(3+1) Group	HIV- (3+0) Group	HIV-(2+1) Group
Number of subjects analysed	83	101	98	98	98
Units: Subjects
Any diarrhoea	8	5	12	10	5
Grade 3 diarrhoea	2	0	3	3	2
Related diarrhoea	8	5	11	9	5
Any drowsiness	49	62	70	70	68
Grade 3 drowsiness	1	6	5	7	8
Related drowsiness	47	58	67	66	63
Fever (axillary) > 39.5°C	0	0	2	0	0
Related fever	33	30	38	27	25
Any irritability	63	84	89	89	91
Grade 3 irritability	6	10	19	13	15
Related irritability	62	80	86	83	85
Any loss of appetite	36	53	56	57	62
Grade 3 loss of appetite	0	1	2	2	5
Related loss of appetite	35	47	53	53	58
Any vomiting	17	19	15	18	23
Grade 3 vomiting	3	3	4	5	2
Related vomiting	16	16	14	13	17
Fever (axillary) ≥ 37.5°C	38	36	41	28	28

No statistical analyses for this end point

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

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End point title

Number of Subjects With Any and Severe (Grade 3) Solicited Local Adverse Events (AEs) ^[2]

End point description

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 > 30 millimeter. The Total Vaccinated cohort included all subjects who received at least one vaccine dose administration, with analysis done solely on subjects for whom post-vaccination results about solicited symptoms were available.

End point type

Secondary

End point timeframe

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

Notes
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting values for the arms that received Synflorix booster vaccination.

End point values	HIV+/+ Group	HIV+/- Group	HIV-(3+1) Group	HIV-(2+1) Group
Number of subjects analysed	74	95	96	96
Units: Subjects
Any pain	40	58	62	60
Grade 3 pain	2	1	2	6
Any redness	25	31	39	45
Redness > 30 mm	5	1	3	0
Any swelling	28	39	38	53
Swelling > 30 mm	5	4	8	10

No statistical analyses for this end point

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

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End point title

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

End point description

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. The Total Vaccinated cohort included all subjects who received at least one vaccine dose administration, with analysis done solely on subjects for whom post-vaccination results about solicited symptoms were available.

End point type

Secondary

End point timeframe

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

Notes
[3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting values for the arms that received Synflorix booster vaccination.

End point values	HIV+/+ Group	HIV+/- Group	HIV-(3+1) Group	HIV-(2+1) Group
Number of subjects analysed	74	95	96	96
Units: Subjects
Any drowsiness	17	28	34	33
Grade 3 drowsiness	2	0	1	1
Related drowsiness	16	27	31	32
Fever > 39.5°C	0	0	0	0
Related fever	8	10	7	10
Any irritability	25	35	31	43
Grade 3 irritability	4	1	1	1
Related irritability	24	35	31	42
Any loss of appetite	17	23	29	37
Grade 3 loss of appetite	0	0	1	2
Related loss of appetite	16	23	29	33
Fever ≥ 37.5°C	9	11	7	11

No statistical analyses for this end point

Secondary: Number of Subjects With Unsolicited AEs

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End point title

Number of Subjects With Unsolicited AEs

End point description

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. The Total Vaccinated cohort included all subjects with at least one vaccine dose administration documented.

End point type

Secondary

End point timeframe

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

End point values	HIV+/+ Group	HIV+/- Group	HIV-(3+1) Group	HIV- (3+0) Group	HIV-(2+1) Group
Number of subjects analysed	83	101	100	100	100
Units: Subjects
Any AE	73	92	93	90	97

No statistical analyses for this end point

Secondary: Number of Subjects With Unsolicited AEs

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End point title

Number of Subjects With Unsolicited AEs ^[4]

End point description

End point type

Secondary

End point timeframe

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

Notes
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting values for the arms that received Synflorix booster vaccination.

End point values	HIV+/+ Group	HIV+/- Group	HIV-(3+1) Group	HIV-(2+1) Group
Number of subjects analysed	76	96	98	98
Units: Subjects
Any AEs	35	47	50	44

No statistical analyses for this end point

Secondary: Number of Subjects With Serious Adverse Events (SAEs)

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End point title

Number of Subjects With Serious Adverse Events (SAEs)

End point description

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. The Total Vaccinated cohort included all subjects with at least one vaccine dose administration documented.

End point type

Secondary

End point timeframe

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

End point values	HIV+/+ Group	HIV+/- Group	HIV-(3+1) Group	HIV- (3+0) Group	HIV-(2+1) Group
Number of subjects analysed	83	101	100	100	100
Units: Subjects
Any SAEs	31	25	20	15	20

No statistical analyses for this end point

Secondary: Concentrations of antibodies against Vaccine Pneumococcal Serotypes

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End point title

Concentrations of antibodies against Vaccine Pneumococcal Serotypes

End point description

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. The According-To-Protocol (ATP) cohort for immunogenicity included evaluable subjects for whom data concerning immunogenicity outcome measures were available. This included subjects for whom assay results were available for antibodies against at least 1 study vaccine antigen component post dose II or III, as applicable, or after booster vaccination.

End point type

Secondary

End point timeframe

At Month 3 and Month 9

End point values	HIV+/+ Group	HIV+/- Group	HIV-(3+1) Group	HIV- (3+0) Group	HIV-(2+1) Group
Number of subjects analysed	70	91	93	94	97
Units: µg/mL
geometric mean (confidence interval 95%)
Anti-1 [Month 3] (N=70,91,93,94,97)	4 (3.3 to 4.84)	3.85 (3.26 to 4.55)	3.36 (2.91 to 3.88)	4.65 (3.91 to 5.53)	3.33 (2.85 to 3.88)
Anti-1 [Month 9] (N=66,89,93,93,97)	6.64 (5.22 to 8.46)	8.64 (7.09 to 10.53)	5.38 (4.47 to 6.48)	0.72 (0.58 to 0.88)	5.14 (4.42 to 5.97)
Anti-4 [Month 3] (N=70,91,93,93,97)	3.67 (2.81 to 4.8)	3.14 (2.6 to 3.8)	2.71 (2.28 to 3.21)	3.77 (3.09 to 4.6)	2.28 (1.9 to 2.75)
Anti-4 [Month 9] (N=66,89,93,93,97)	6.97 (5.72 to 8.5)	8.04 (6.69 to 9.68)	6.07 (5.09 to 7.24)	1.07 (0.86 to 1.34)	4.92 (4.16 to 5.81)
Anti-5 [Month 3] (N=70,91,93,94,97)	4.99 (4 to 6.23)	4.79 (3.96 to 5.79)	4.41 (3.79 to 5.13)	5.71 (4.84 to 6.75)	3.45 (2.85 to 4.16)
Anti-5 [Month 9] (N=66,89,93,93,97)	7.86 (6.25 to 9.89)	9.48 (7.84 to 11.46)	8.05 (6.7 to 9.66)	1.44 (1.16 to 1.77)	6.96 (5.89 to 8.22)
Anti-6B [Month 3] (N=70,91,93,93,97)	1 (0.73 to 1.38)	0.94 (0.71 to 1.24)	0.65 (0.5 to 0.86)	1.06 (0.81 to 1.39)	0.57 (0.45 to 0.73)
Anti-6B [Month 9] (N=66,89,93,93,97)	2.26 (1.72 to 2.98)	2.56 (2.01 to 3.25)	2.05 (1.57 to 2.68)	0.93 (0.75 to 1.15)	1.98 (1.62 to 2.42)
Anti-7F [Month 3] (N=70,91,93,94,97)	4.95 (3.82 to 6.41)	3.69 (3.08 to 4.41)	3.62 (3.12 to 4.19)	4.77 (4.06 to 5.6)	2.72 (2.3 to 3.22)
Anti-7F [Month 9] (N=66,89,93,93,97)	9.92 (7.89 to 12.47)	11.04 (9.29 to 13.11)	8.98 (7.63 to 10.56)	1.78 (1.49 to 2.13)	6.47 (5.59 to 7.5)
Anti-9V [Month 3] (N=70,91,93,94,97)	4.53 (3.39 to 6.05)	4.25 (3.49 to 5.16)	3.04 (2.51 to 3.69)	5.13 (4.35 to 6.04)	2.05 (1.61 to 2.61)
Anti-9V [Month 9] (N=66,89,93,93,97)	10.09 (7.64 to 13.32)	10.89 (9.11 to 13.03)	9.55 (8.06 to 11.31)	1.96 (1.58 to 2.43)	6.51 (5.12 to 8.3)
Anti-14 [Month 3] (N=70,91,93,93,97)	7.25 (5.37 to 9.81)	6.77 (5.43 to 8.44)	3.85 (3.18 to 4.68)	5.27 (4.31 to 6.45)	2.51 (1.98 to 3.19)
Anti-14 [Month 9] (N=66,89,93,93,97)	11.5 (9.17 to 14.41)	10.58 (8.6 to 13)	7.33 (5.94 to 9.04)	2.6 (2.01 to 3.37)	5.08 (4.03 to 6.41)
Anti-18C [Month 3] (N=69,91,93,94,97)	9.55 (7.19 to 12.67)	9.48 (7.41 to 12.13)	10.08 (8.25 to 12.31)	13.2 (10.31 to 16.9)	8.65 (6.44 to 11.6)
Anti-18C [Month 9] (N=66,89,93,93,97)	20.26 (16.13 to 25.45)	19.67 (15.89 to 24.35)	25.47 (21.75 to 29.83)	3.3 (2.55 to 4.27)	32.29 (26.43 to 39.45)
Anti-19F [Month 3] (N=70,91,93,93,96)	5.7 (4.06 to 8.02)	11.15 (8.88 to 13.99)	8.75 (7.37 to 10.38)	10.93 (9.2 to 12.99)	6.9 (5.62 to 8.48)
Anti-19F [Month 9] (N=66,89,93,93,97)	8 (5.86 to 10.92)	12.46 (10.47 to 14.84)	8.88 (7.37 to 10.69)	2.6 (2.03 to 3.31)	9.47 (7.42 to 12.07)
Anti-23F [Month 3] (N=70,91,93,93,97)	1.71 (1.23 to 2.37)	1.52 (1.14 to 2.01)	0.92 (0.72 to 1.19)	1.59 (1.21 to 2.09)	0.97 (0.74 to 1.27)
Anti-23F [Month 9] (N=66,89,93,93,97)	4 (2.69 to 5.93)	5.9 (4.37 to 7.96)	3.83 (2.84 to 5.15)	0.92 (0.68 to 1.23)	3.4 (2.67 to 4.33)

No statistical analyses for this end point

Secondary: Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes

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End point title

Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes

End point description

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. The According-To-Protocol cohort for immunogenicity included evaluable subjects for whom data concerning immunogenicity outcome measures were available. This included subjects for whom assay results were available for antibodies against at least 1 study vaccine antigen component post dose II or III, as applicable, or after booster vaccination.

End point type

Secondary

End point timeframe

Up to study end at Month 23 (24-27 months of age)

End point values	HIV+/+ Group	HIV+/- Group	HIV-(3+1) Group	HIV- (3+0) Group	HIV-(2+1) Group
Number of subjects analysed	63	86	92	91	97
Units: µg/mL
geometric mean (confidence interval 95%)
Anti-1 (N=63,86,92,90,97)	0.53 (0.35 to 0.8)	0.74 (0.57 to 0.95)	0.42 (0.34 to 0.53)	0.28 (0.22 to 0.37)	0.33 (0.26 to 0.41)
Anti-4 (N=63,86,92,91,97)	0.56 (0.38 to 0.8)	0.57 (0.46 to 0.71)	0.44 (0.35 to 0.57)	0.33 (0.25 to 0.44)	0.34 (0.27 to 0.43)
Anti-5 (N=63,86,92,90,97)	0.79 (0.55 to 1.15)	0.77 (0.61 to 0.97)	0.72 (0.57 to 0.92)	0.45 (0.36 to 0.57)	0.52 (0.43 to 0.64)
Anti-6B (N=63,86,92,91,97)	0.67 (0.42 to 1.06)	0.73 (0.56 to 0.97)	0.6 (0.47 to 0.77)	0.76 (0.56 to 1.03)	0.57 (0.44 to 0.74)
Anti-7F (N=63,86,92,91,97)	1.25 (0.9 to 1.75)	1.16 (0.96 to 1.39)	1.08 (0.92 to 1.27)	0.67 (0.54 to 0.83)	0.84 (0.7 to 1)
Anti-9V (N=63,86,92,91,97)	1.15 (0.77 to 1.71)	1.3 (1.04 to 1.63)	1.05 (0.86 to 1.28)	0.85 (0.68 to 1.06)	0.8 (0.64 to 1)
Anti-14 (N=63,86,92,91,97)	2.62 (2.02 to 3.4)	2.09 (1.69 to 2.58)	1.32 (1.07 to 1.64)	1.24 (0.96 to 1.61)	1.06 (0.83 to 1.36)
Anti-18C (N=63,86,92,91,97)	2.02 (1.41 to 2.89)	1.6 (1.22 to 2.09)	1.93 (1.58 to 2.35)	0.8 (0.63 to 1.01)	2.44 (1.97 to 3.02)
Anti-19F (N=63,86,92,91,97)	2.01 (1.32 to 3.08)	2.28 (1.72 to 3.02)	2.53 (1.91 to 3.34)	1.59 (1.15 to 2.2)	2.22 (1.74 to 2.84)
Anti-23F (N=63,86,92,90,97)	0.73 (0.49 to 1.09)	0.85 (0.63 to 1.14)	0.51 (0.39 to 0.67)	0.53 (0.38 to 0.73)	0.52 (0.37 to 0.72)

No statistical analyses for this end point

Secondary: Opsonophagocytic Titers against Vaccine Pneumococcal Serotypes

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End point title

Opsonophagocytic Titers against Vaccine Pneumococcal Serotypes

End point description

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. The According-To-Protocol cohort for immunogenicity included evaluable subjects for whom data concerning immunogenicity outcome measures were available. This included subjects for whom assay results were available for antibodies against at least 1 study vaccine antigen component post dose II or III, as applicable, or after booster vaccination.

End point type

Secondary

End point timeframe

At Month 3 and Month 9

End point values	HIV+/+ Group	HIV+/- Group	HIV-(3+1) Group	HIV- (3+0) Group	HIV-(2+1) Group
Number of subjects analysed	68	91	93	92	96
Units: Titers
geometric mean (confidence interval 95%)
Opsono-1 [Month 3] (N=68,91,93,92,96)	139.7 (85.2 to 229)	147.6 (102.9 to 211.7)	127.2 (86.2 to 187.8)	268.7 (196.7 to 366.9)	160.6 (117.8 to 218.8)
Opsono-1 [Month 9] (N=63,85,90,89,94)	1061.5 (680.5 to 1655.8)	1377.8 (984.9 to 1927.4)	1014.8 (768.4 to 1340.3)	23.5 (16.1 to 34.4)	1003.6 (763.2 to 1319.8)
Opsono-4 [Month 3] (N=67,91,93,92,96)	671.6 (430.7 to 1047.5)	1518.1 (1149.7 to 2004.4)	1711.9 (1367.7 to 2142.9)	1890.6 (1547.2 to 2310.2)	774.8 (596.7 to 1006)
Opsono-4 [Month 9] (N=62,86,90,87,95)	2034.2 (1593.5 to 2596.9)	3259 (2579.2 to 4117.9)	2484.7 (1919 to 3217.1)	112.3 (70.8 to 178.1)	1717.6 (1406 to 2098.2)
Opsono-5 [Month 3] (N=68,91,93,92,96)	105.7 (73.8 to 151.4)	128.6 (97.5 to 169.5)	107.4 (81.8 to 141)	189.2 (147 to 243.5)	105.7 (81.6 to 136.8)
Opsono-5 [Month 9] (N=63,85,90,90,94)	540.4 (366.4 to 796.9)	531.1 (397.3 to 710)	630.2 (447.5 to 887.7)	30.5 (21.8 to 42.5)	472.7 (343.5 to 650.5)
Opsono-6B [Month 3] (N=68,90,92,91,92)	239.7 (123 to 467.4)	480.5 (282.1 to 818.5)	499.5 (286.1 to 872.2)	1213.7 (808.2 to 1822.6)	361.2 (221.8 to 588.2)
Opsono-6B [Month 9] (N=60,84,88,86,94)	853 (467.8 to 1555.3)	986.6 (667.6 to 1457.9)	1047.2 (679.3 to 1614.4)	261.5 (161 to 424.7)	945.9 (640 to 1398.2)
Opsono-7F [Month 3] (N=68,90,92,92,95)	4025.2 (2609.7 to 6208.4)	10158.3 (7772 to 13277.2)	5910.5 (4696.9 to 7437.6)	6834.5 (5280.8 to 8845.4)	2650 (2002 to 3507.9)
Opsono-7F [Month 9] (N=63,85,88,90,95)	10656.1 (7729.9 to 14690)	18816.6 (14352.2 to 24669.7)	12108.8 (9922.2 to 14777.4)	2741.1 (2173.7 to 3456.5)	6029.3 (4760.9 to 7635.6)
Opsono-9V [Month 3] (N=68,90,93,92,96)	1197.2 (796.2 to 1800.1)	1736.5 (1224.1 to 2463.5)	1672.2 (1243.6 to 2248.4)	2216 (1760.9 to 2788.8)	1068.2 (759.2 to 1503)
Opsono-9V [Month 9] (N=64,86,91,90,94)	2436.8 (1736.5 to 3419.7)	3215.4 (2515.8 to 4109.6)	4250.1 (3493.4 to 5170.8)	492.3 (351.2 to 690.1)	2572.5 (1890.3 to 3500.8)
Opsono-14 [Month 3] (N=68,90,92,92,95)	2656.2 (1686.7 to 4183)	3175.1 (2472.8 to 4077)	1902.7 (1300.9 to 2782.9)	2205 (1648.8 to 2948.7)	380.9 (228.1 to 636)
Opsono-14 [Month 9] (N=65,87,89,87,94)	2205.9 (1570.2 to 3099)	2374.3 (1923.2 to 2931.2)	2180 (1781.9 to 2667)	280 (183 to 428.6)	1152.9 (910.6 to 1459.6)
Opsono-18C [Month 3] (N=68,91,91,92,93)	438.7 (284.1 to 677.3)	575.9 (442.9 to 748.8)	1046.9 (802.6 to 1365.5)	1203.2 (981.2 to 1475.4)	1052.3 (777.7 to 1423.8)
Opsono-18C [Month 9] (N=62,85,90,90,93)	1039.3 (770.2 to 1402.3)	1036.5 (800.1 to 1342.7)	1344.4 (1074.6 to 1681.9)	64.5 (44.1 to 94.3)	1441.3 (1111.7 to 1868.5)
Opsono-19F [Month 3] (N=68,91,92,92,95)	228.6 (132.5 to 394.4)	590.3 (418.9 to 831.6)	511.9 (394.1 to 664.9)	649.3 (481.1 to 876.2)	275.9 (193.4 to 393.5)
Opsono-19F [Month 9] (N=61,86,89,88,94)	488.2 (275.3 to 865.9)	1357.5 (976.2 to 1887.8)	730.8 (516.5 to 1034.1)	46.8 (31.6 to 69.5)	630.3 (422.9 to 939.5)
Opsono-23F [Month 3] (N=68,89,88,92,91)	338 (174.1 to 656.2)	769.6 (451.1 to 1312.9)	864.1 (511.2 to 1460.6)	1107 (683 to 1794)	509.6 (306.8 to 846.6)
Opsono-23F [Month 9] (N=63,87,90,86,95)	1327.4 (736.2 to 2393.5)	2120.7 (1359.4 to 3308.1)	2144.8 (1312.5 to 3504.8)	83.6 (47.2 to 148)	1557.2 (1012.2 to 2395.7)

No statistical analyses for this end point

Secondary: Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes

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End point title

Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes

End point description

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. The According-To-Protocol cohort for immunogenicity included evaluable subjects for whom data concerning immunogenicity outcome measures were available. This included subjects for whom assay results were available for antibodies against at least 1 study vaccine antigen component post dose II or III, as applicable, or after booster vaccination.

End point type

Secondary

End point timeframe

Up to study end at Month 23 (24-27 months of age)

End point values	HIV+/+ Group	HIV+/- Group	HIV-(3+1) Group	HIV- (3+0) Group	HIV-(2+1) Group
Number of subjects analysed	59	84	89	86	91
Units: Titers
geometric mean (confidence interval 95%)
Opsono-1 (N=59,84,89,85,91)	36.7 (19.6 to 68.9)	28.1 (17.4 to 45.4)	22.8 (14.9 to 34.9)	12.3 (8.2 to 18.6)	13.9 (9.8 to 19.7)
Opsono-4 (N=53,74,82,79,83)	76.6 (36.8 to 159.5)	141.7 (79.2 to 253.5)	125.5 (69.1 to 228.2)	21.6 (12.4 to 37.5)	58.8 (33 to 105)
Opsono-5 (N=57,82,88,86,89)	22.5 (13.7 to 37)	19.1 (13.9 to 26.2)	19.5 (14.2 to 26.7)	8.6 (6.5 to 11.3)	13.3 (10.2 to 17.3)
Opsono-6B (N=54,81,80,79,83)	100 (48.8 to 204.7)	75.5 (44.2 to 128.8)	116.6 (63.7 to 213.3)	87.2 (48.2 to 157.7)	55.9 (32 to 97.7)
Opsono-7F (N=55,80,81,77,81)	6367.5 (4511.3 to 8987.6)	7396.6 (5736.2 to 9537.6)	6365 (5177.2 to 7825.4)	5601.1 (4334.9 to 7237.3)	5859.9 (4371.4 to 7855.2)
Opsono-9V (N=53,80,85,84,89)	507.6 (315.2 to 817.5)	598.6 (396.9 to 902.7)	1060.7 (761.2 to 1478.1)	412.3 (267.4 to 635.9)	465.7 (318.2 to 681.6)
Opsono-14 (N=56,79,84,76,80)	452 (270.6 to 755)	472.8 (305.1 to 732.6)	362.3 (229.7 to 571.6)	361.5 (213.2 to 613.2)	185.2 (105.8 to 324.1)
Opsono-18C (N=56,71,80,83,78)	21.1 (13 to 34.4)	26.7 (17.1 to 41.6)	48.7 (30.4 to 78.1)	9.8 (6.6 to 14.5)	41.6 (27.3 to 63.3)
Opsono-19F (N=55,74,86,82,85)	41.8 (23.5 to 74.4)	73.2 (47.1 to 114)	52.5 (33.2 to 83.1)	28.2 (17.8 to 44.6)	47.6 (30.1 to 75.1)
Opsono-23F (N=53,78,80,78,80)	97.6 (38.2 to 249.6)	154.8 (71.7 to 334.2)	69.7 (31.7 to 153.1)	92.7 (40.7 to 211.2)	103.5 (47 to 227.7)

No statistical analyses for this end point

Secondary: Concentrations of Antibodies against Cross-reactive Pneumococcal Serotypes 6A and 19A

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End point title

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

End point description

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. The According-To-Protocol cohort for immunogenicity included evaluable subjects for whom data concerning immunogenicity outcome measures were available. This included subjects for whom assay results were available for antibodies against at least 1 study vaccine antigen component post dose II or III, as applicable, or after booster vaccination.

End point type

Secondary

End point timeframe

At Month 3 and Month 9

End point values	HIV+/+ Group	HIV+/- Group	HIV-(3+1) Group	HIV- (3+0) Group	HIV-(2+1) Group
Number of subjects analysed	70	91	93	93	97
Units: µg/mL
geometric mean (confidence interval 95%)
Anti-6A [Month 3] (N=70,91,93,93,97)	0.15 (0.12 to 0.19)	0.12 (0.1 to 0.15)	0.12 (0.1 to 0.15)	0.13 (0.11 to 0.16)	0.11 (0.09 to 0.13)
Anti-6A [Month 9] (N=66,89,93,93,97)	0.48 (0.34 to 0.67)	0.58 (0.43 to 0.77)	0.36 (0.27 to 0.49)	0.21 (0.15 to 0.28)	0.36 (0.28 to 0.47)
Anti-19A [Month 3] (N=69,91,93,92,97)	0.16 (0.12 to 0.23)	0.28 (0.21 to 0.36)	0.2 (0.16 to 0.25)	0.29 (0.23 to 0.38)	0.25 (0.2 to 0.32)
Anti-19A [Month 9] (N=66,89,93,93,97)	0.99 (0.61 to 1.61)	1.48 (1.06 to 2.08)	0.78 (0.57 to 1.07)	0.26 (0.19 to 0.37)	1.04 (0.72 to 1.49)

No statistical analyses for this end point

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

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End point title

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

End point description

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. The According-To-Protocol cohort for immunogenicity included evaluable subjects for whom data concerning immunogenicity outcome measures were available. This included subjects for whom assay results were available for antibodies against at least 1 study vaccine antigen component post dose II or III, as applicable, or after booster vaccination.

End point type

Secondary

End point timeframe

Up to study end at Month 23 (24-27 months of age)

End point values	HIV+/+ Group	HIV+/- Group	HIV-(3+1) Group	HIV- (3+0) Group	HIV-(2+1) Group
Number of subjects analysed	63	86	92	91	97
Units: µg/mL
geometric mean (confidence interval 95%)
Anti-6A (N=63,86,92,91,97)	0.23 (0.14 to 0.38)	0.25 (0.17 to 0.35)	0.2 (0.15 to 0.27)	0.25 (0.18 to 0.36)	0.19 (0.14 to 0.26)
Anti-19A (N=63,86,92,89,97)	0.45 (0.26 to 0.76)	0.47 (0.31 to 0.72)	0.53 (0.35 to 0.8)	0.41 (0.28 to 0.6)	0.58 (0.41 to 0.83)

No statistical analyses for this end point

Secondary: Opsonophagocytic Titers against Cross-reactive Pneumococcal Serotypes 6A and 19A

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End point title

Opsonophagocytic Titers against Cross-reactive Pneumococcal Serotypes 6A and 19A

End point description

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. ATP cohort for immunogenicity included evaluable subjects for whom data concerning immunogenicity outcome measures were available. This included subjects for whom assay results were available for antibodies against at least 1 study vaccine antigen component post dose II or III, as applicable, or after booster vaccination.

End point type

Secondary

End point timeframe

At Month 3 and Month 9

End point values	HIV+/+ Group	HIV+/- Group	HIV-(3+1) Group	HIV- (3+0) Group	HIV-(2+1) Group
Number of subjects analysed	67	91	93	91	95
Units: Titers
geometric mean (confidence interval 95%)
Opsono -6A [Month 3] (N=67,91,89,91,95)	7.7 (5.2 to 11.5)	11.5 (7.4 to 17.9)	12.1 (7.8 to 18.9)	13.8 (9.1 to 20.9)	8.1 (5.8 to 11.3)
Opsono -6A [Month 9] (N=64,86,83,86,94)	26.4 (14.7 to 47.3)	38.6 (22.2 to 67)	40.4 (22.9 to 71.4)	9.5 (6.5 to 14)	42.2 (25.5 to 69.9)
Opsono -19A [Month 3] (N=66,91,93,90,95)	9.5 (6.4 to 14)	15.2 (10.4 to 22.2)	10.6 (7.7 to 14.7)	14.2 (9.7 to 20.8)	7.8 (5.9 to 10.2)
Opsono -19A [Month 9] (N=63,86,89,89,92)	42 (24.8 to 71.2)	101.8 (63.9 to 162.3)	38.3 (24.1 to 60.9)	7.9 (5.7 to 10.9)	36.1 (22.3 to 58.3)

No statistical analyses for this end point

Secondary: Opsonophagocytic Titers against Cross-reactive Pneumococcal Serotypes 6A and 19A

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End point title

Opsonophagocytic Titers against Cross-reactive Pneumococcal Serotypes 6A and 19A

End point description

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. The According-To-Protocol cohort for immunogenicity included evaluable subjects for whom data concerning immunogenicity outcome measures were available. This included subjects for whom assay results were available for antibodies against at least 1 study vaccine antigen component post dose II or III, as applicable, or after booster vaccination.

End point type

Secondary

End point timeframe

Up to study end at Month 23 (24-27 months of age)

End point values	HIV+/+ Group	HIV+/- Group	HIV-(3+1) Group	HIV- (3+0) Group	HIV-(2+1) Group
Number of subjects analysed	56	79	80	82	81
Units: Titers
geometric mean (confidence interval 95%)
Opsono-6A (N=53,79,79,79,79)	14.2 (7.5 to 27.2)	15.7 (9.4 to 26.2)	20.5 (12.2 to 34.3)	15.3 (8.5 to 27.5)	19 (11.4 to 31.9)
Opsono-19A (N=56,79,80,82,81)	19.9 (11.4 to 34.8)	15.8 (10 to 24.8)	25.1 (15.1 to 41.9)	14.5 (9.4 to 22.6)	16.8 (10.9 to 26)

No statistical analyses for this end point

Secondary: Concentrations of Antibodies Against Protein D (PD) by ELISA

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End point title

Concentrations of Antibodies Against Protein D (PD) by ELISA

End point description

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. The According-To-Protocol cohort for immunogenicity included evaluable subjects for whom data concerning immunogenicity outcome measures were available. This included subjects for whom assay results were available for antibodies against at least 1 study vaccine antigen component post dose II or III, as applicable, or after booster vaccination.

End point type

Secondary

End point timeframe

At Month 3 and Month 9

End point values	HIV+/+ Group	HIV+/- Group	HIV-(3+1) Group	HIV- (3+0) Group	HIV-(2+1) Group
Number of subjects analysed	70	91	93	94	97
Units: EL.U/mL
geometric mean (confidence interval 95%)
Anti-PD [Month 3] (N=70,91,93,94,97)	4215.1 (3622.3 to 4905)	3397.6 (2917.2 to 3957.1)	3431.8 (2955.1 to 3985.4)	4253.1 (3721 to 4861.4)	2240 (1871 to 2681.9)
Anti-PD [Month 9] (N=66,89,93,93,97)	5443.1 (4705.1 to 6297)	5018.3 (4335.7 to 5808.5)	4576.5 (3938.2 to 5318.3)	930.4 (770 to 1124.2)	3141 (2619 to 3767)

No statistical analyses for this end point

Secondary: Concentrations of Antibodies Against Protein D (PD) by ELISA

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End point title

Concentrations of Antibodies Against Protein D (PD) by ELISA

End point description

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. The According-To-Protocol cohort for immunogenicity included evaluable subjects for whom data concerning immunogenicity outcome measures were available. This included subjects for whom assay results were available for antibodies against at least 1 study vaccine antigen component post dose II or III, as applicable, or after booster vaccination.

End point type

Secondary

End point timeframe

Up to study end at Month 23 (24-27 months of age)

End point values	HIV+/+ Group	HIV+/- Group	HIV-(3+1) Group	HIV- (3+0) Group	HIV-(2+1) Group
Number of subjects analysed	63	86	92	91	97
Units: EL.U/mL
geometric mean (confidence interval 95%)
Anti-PD (N=63,86,92,91,97)	748.3 (581.8 to 962.3)	615.3 (495.8 to 763.4)	503.2 (421 to 601.5)	421.3 (334.2 to 531.1)	323 (255.6 to 408.1)

No statistical analyses for this end point

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

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End point title

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

End point description

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. The According-To-Protocol cohort for immunogenicity included evaluable subjects for whom data concerning immunogenicity outcome measures were available. This included subjects for whom assay results were available for antibodies against at least 1 study vaccine antigen component post dose II or III, as applicable, or after booster vaccination.

End point type

Secondary

End point timeframe

1 month following primary immunization (at Month 3)

End point values	HIV+/+ Group	HIV+/- Group	HIV-(3+1) Group	HIV- (3+0) Group	HIV-(2+1) Group
Number of subjects analysed	70	91	93	94	97
Units: IU/mL
geometric mean (confidence interval 95%)
Anti-DT (N=70,91,93,93,97)	2.42 (1.92 to 3.06)	3.69 (3.19 to 4.26)	3.42 (2.96 to 3.96)	4.2 (3.76 to 4.68)	3 (2.58 to 3.49)
Anti-TT (N=70,91,93,94,97)	5.03 (4.16 to 6.07)	4.77 (4.03 to 5.63)	4.5 (3.89 to 5.21)	5.03 (4.33 to 5.85)	4.24 (3.5 to 5.14)

No statistical analyses for this end point

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

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End point title

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

End point description

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. The According-To-Protocol cohort for immunogenicity at 15-18 months included evaluable subjects from the ATP cohort for Immunogenicity who received the DTPw-HBV/Hib vaccine and for whom assay results were available for antibodies against at least 1 vaccine antigen component after this booster dose vaccine.

End point type

Secondary

End point timeframe

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

End point values	HIV+/+ Group	HIV+/- Group	HIV-(3+1) Group	HIV- (3+0) Group	HIV-(2+1) Group
Number of subjects analysed	59	81	91	87	92
Units: IU/mL
geometric mean (confidence interval 95%)
Anti-DT (N=59,81,91,87,92)	9.57 (7.91 to 11.59)	11.7 (10.28 to 13.32)	10.45 (9.18 to 11.89)	12.67 (10.82 to 14.83)	11.96 (10.48 to 13.64)
Anti-TT (N=59,81,91,87,92)	14.44 (12.2 to 17.09)	14.6 (12.58 to 16.95)	16.19 (14.18 to 18.48)	17.69 (15.57 to 20.11)	19.77 (17.74 to 22.04)

No statistical analyses for this end point

Secondary: Concentrations of Antibodies Against Bordetella Pertussis (BPT) by ELISA

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End point title

Concentrations of Antibodies Against Bordetella Pertussis (BPT) by ELISA

End point description

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. The According-To-Protocol cohort for immunogenicity included evaluable subjects for whom data concerning immunogenicity outcome measures were available. This included subjects for whom assay results were available for antibodies against at least 1 study vaccine antigen component post dose II or III, as applicable, or after booster vaccination.

End point type

Secondary

End point timeframe

1 month following primary immunization (at Month 3)

End point values	HIV+/+ Group	HIV+/- Group	HIV-(3+1) Group	HIV- (3+0) Group	HIV-(2+1) Group
Number of subjects analysed	70	91	93	92	97
Units: EL.U/mL
geometric mean (confidence interval 95%)
Anti-BPT (N=70,91,93,92,97)	90.86 (74.89 to 110.23)	132.27 (118.6 to 147.51)	143.08 (129.44 to 158.17)	152.23 (137.86 to 168.1)	146.6 (129.19 to 166.34)

No statistical analyses for this end point

Secondary: Concentrations of Antibodies Against Bordetella Pertussis (BPT) by ELISA

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End point title

Concentrations of Antibodies Against Bordetella Pertussis (BPT) by ELISA

End point description

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. The ATP cohort for immunogenicityat 15-18 months included evaluable subjects from the ATP cohort for Immunogenicity who received the DTPw-HBV/Hib vaccine and for whom assay results were available for antibodies against at least 1 vaccine antigen component after this booster dose vaccine.

End point type

Secondary

End point timeframe

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

End point values	HIV+/+ Group	HIV+/- Group	HIV-(3+1) Group	HIV- (3+0) Group	HIV-(2+1) Group
Number of subjects analysed	59	81	90	87	92
Units: EL.U/mL
geometric mean (confidence interval 95%)
Anti-BPT (N=59,81,90,87,92)	161.01 (131.88 to 196.58)	227.01 (202.86 to 254.03)	241.77 (218.18 to 267.9)	259.45 (234.7 to 286.81)	267.8 (243.49 to 294.54)

No statistical analyses for this end point

Secondary: Concentrations of Antibodies against Polyribosyl-ribitol Phosphate (PRP)

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End point title

Concentrations of Antibodies against Polyribosyl-ribitol Phosphate (PRP)

End point description

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. The According-To-Protocol cohort for immunogenicity included evaluable subjects for whom data concerning immunogenicity outcome measures were available. This included subjects for whom assay results were available for antibodies against at least 1 study vaccine antigen component post dose II or III, as applicable, or after booster vaccination.

End point type

Secondary

End point timeframe

1 month following primary immunization (at Month 3)

End point values	HIV+/+ Group	HIV+/- Group	HIV-(3+1) Group	HIV- (3+0) Group	HIV-(2+1) Group
Number of subjects analysed	70	91	93	93	97
Units: µg/mL
geometric mean (confidence interval 95%)
Anti- PRP (N=70,91,93,93,97)	16.71 (11.63 to 24.01)	20.55 (15.78 to 26.78)	20.36 (15.56 to 26.64)	24.22 (18.45 to 31.8)	21.78 (16.47 to 28.79)

No statistical analyses for this end point

Secondary: Concentrations of Antibodies against Polyribosyl-ribitol Phosphate (PRP)

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End point title

Concentrations of Antibodies against Polyribosyl-ribitol Phosphate (PRP)

End point description

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. The ATP cohort for immunogenicity at 15 -18 months included evaluable subjects from the ATP cohort for Immunogenicity who received the DTPw-HBV/Hib vaccine and for whom assay results were available for antibodies against at least 1 vaccine antigen component after this booster dose vaccine.

End point type

Secondary

End point timeframe

1 month after the booster vaccination (at Month 15)

End point values	HIV+/+ Group	HIV+/- Group	HIV-(3+1) Group	HIV- (3+0) Group	HIV-(2+1) Group
Number of subjects analysed	59	80	91	87	92
Units: µg/mL
geometric mean (confidence interval 95%)
Anti-PRP (N=59,80,91,87,92)	50.11 (33.29 to 75.43)	71.23 (55.03 to 92.19)	83.46 (64.51 to 107.98)	93.18 (69.67 to 124.64)	129.99 (103.73 to 162.89)

No statistical analyses for this end point

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

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End point title

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

End point description

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. The According-To-Protocol cohort for immunogenicity included evaluable subjects for whom data concerning immunogenicity outcome measures were available. This included subjects for whom assay results were available for antibodies against at least 1 study vaccine antigen component post dose II or III, as applicable, or after booster vaccination.

End point type

Secondary

End point timeframe

1 month following primary immunization (at Month 3)

End point values	HIV+/+ Group	HIV+/- Group	HIV-(3+1) Group	HIV- (3+0) Group	HIV-(2+1) Group
Number of subjects analysed	63	85	88	87	90
Units: mIU/mL
geometric mean (confidence interval 95%)
Anti-HBs (N=63,85,88,87,90)	288.45 (167.12 to 497.86)	478.53 (333.22 to 687.22)	865.5 (654.8 to 1144.1)	904.7 (646 to 1267)	563.5 (373.8 to 849.4)

No statistical analyses for this end point

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

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End point title

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

End point description

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. The ATP cohort for immunogenicity at 15-18 months included evaluable subjects from the ATP cohort for Immunogenicity who received the DTPw-HBV/Hib vaccine and for whom assay results were available for antibodies against at least 1 vaccine antigen component after this booster dose vaccine.

End point type

Secondary

End point timeframe

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

End point values	HIV+/+ Group	HIV+/- Group	HIV-(3+1) Group	HIV- (3+0) Group	HIV-(2+1) Group
Number of subjects analysed	58	78	90	81	89
Units: mIU/mL
geometric mean (confidence interval 95%)
Anti-HBs (N=58,78,90,81,89)	1871 (892.9 to 3920.7)	2507.4 (1500.7 to 4189.4)	3674.4 (2446.9 to 5517.9)	4287.6 (2785.9 to 6598.8)	3583.4 (2194.8 to 5850.6)

No statistical analyses for this end point

Secondary: Concentrations of Antibodies against Rotavirus Immunoglobulin A (Rotavirus IgA), by Rotarix Vaccination Status

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End point title

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

End point description

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. The According-To-Protocol cohort for immunogenicity included evaluable subjects for whom data concerning immunogenicity outcome measures were available. This included subjects for whom assay results were available for antibodies against at least 1 study vaccine antigen component post dose II or III, as applicable, or after booster vaccination.

End point type

Secondary

End point timeframe

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

End point values	HIV+/+ Group	HIV+/- Group	HIV-(3+1) Group	HIV- (3+0) Group	HIV-(2+1) Group
Number of subjects analysed	58	59	66	66	67
Units: U/mL
geometric mean (confidence interval 95%)
Anti-rotavirus IgA [2 doses] (N=58,59,66,66,67)	52.6 (33.8 to 81.8)	104.1 (66.3 to 163.5)	146.4 (94.2 to 227.4)	92 (60 to 141)	74.3 (47.5 to 116.3)
Anti-rotavirus IgA [1 dose] (N=0,0,1,1,0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)
Anti-rotavirus IgA [0 dose] (N=11,27,25,24,28)	54.8 (13.1 to 229.2)	54 (21.3 to 136.8)	63.1 (34.8 to 114.5)	47.5 (26.5 to 85.3)	41.7 (22.3 to 78.1)

No statistical analyses for this end point

Secondary: Concentrations of Antibodies Against Measles

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End point title

Concentrations of Antibodies Against Measles

End point description

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. The According-To-Protocol cohort for immunogenicity included evaluable subjects for whom data concerning immunogenicity outcome measures were available. This included subjects for whom assay results were available for antibodies against at least 1 study vaccine antigen component post dose II or III, as applicable, or after booster vaccination.

End point type

Secondary

End point timeframe

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

End point values	HIV+/+ Group	HIV+/- Group	HIV-(3+1) Group	HIV- (3+0) Group	HIV-(2+1) Group
Number of subjects analysed	63	85	91	87	93
Units: mIU/mL
geometric mean (confidence interval 95%)
Anti-Measles [Month 9](N=54,79,82,83,87)	2013.36 (1566.36 to 2587.94)	1917.14 (1468.59 to 2502.68)	1973.84 (1512.9 to 2575.22)	1509.36 (1157.32 to 1968.5)	1719.76 (1360.39 to 2174.08)
Anti-Measles [Month 15](N=63,85,91,87,93)	3358.15 (2578.34 to 4373.83)	4189.83 (3451.63 to 5085.91)	3713.51 (3050.3 to 4520.92)	3311.3 (2698.56 to 4063.17)	3204.79 (2659 to 3862.61)

No statistical analyses for this end point

Secondary: Anti-LytC IgA and Anti-PhtD IgA antibodies concentrations in salivary samples

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End point title

Anti-LytC IgA and Anti-PhtD IgA antibodies concentrations in salivary samples

End point description

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 was sent to RMPRU (or GSK Biologicals’ designated validated laboratory) where the sponge was centrifuged to extract the saliva 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. The Total Vaccinated cohort included all subjects with at least one vaccine dose administration documented.

End point type

Secondary

End point timeframe

Up to study end at Month 23 (24-27 months of age)

End point values	HIV+/+ Group	HIV+/- Group	HIV-(3+1) Group	HIV- (3+0) Group	HIV-(2+1) Group
Number of subjects analysed	77	95	98	94	98
Units: U/mL
geometric mean (confidence interval 95%)
Anti-LytC [Month0] (N=65,50,46,46,45)	7.71 (5.44 to 10.95)	5.49 (3.81 to 7.91)	6.22 (4.35 to 8.9)	5.98 (4.24 to 8.43)	6.67 (4.89 to 9.08)
Anti-LytC [Month3] (N=74,79,95,91,93)	18.3 (13.29 to 25.22)	13.48 (10.46 to 17.37)	13.29 (10.5 to 16.82)	13.81 (10.56 to 18.06)	14.43 (11.32 to 18.39)
Anti-LytC [Month8] (N=75,95,98,94,98)	27.23 (18.88 to 39.29)	15.99 (12.29 to 20.79)	24.51 (18.63 to 32.24)	22.64 (16.56 to 30.96)	21.85 (16.32 to 29.25)
Anti-LytC [Month9] (N=77,94,98,94,97)	30.96 (20.88 to 45.88)	15.54 (11.72 to 20.61)	24.6 (17.89 to 33.83)	21.06 (15.15 to 29.27)	25 (18.66 to 33.5)
Anti-LytC [Month11] (N=77,93,98,93,97)	37.01 (24.64 to 55.59)	18.79 (13.94 to 25.32)	43.03 (30.64 to 60.44)	35.65 (26.47 to 48.02)	38.07 (28.23 to 51.34)
Anti-LytC [Month14] (N=73,94,98,94,97)	39.45 (28.22 to 55.15)	24.69 (18.48 to 32.97)	39.59 (28.87 to 54.29)	38.87 (29.26 to 51.63)	34.75 (26.4 to 45.74)
Anti-LytC [Month15] (N=74,93,97,93,98)	58.11 (38.95 to 86.69)	28.09 (21.12 to 37.36)	42.43 (31.21 to 57.68)	50.45 (38.7 to 65.77)	42.98 (32.28 to 57.22)
Anti-LytC [Month23] (N=73,91,97,92,98)	89.32 (63.92 to 124.81)	43.61 (32.16 to 59.14)	68.34 (51.15 to 91.32)	61.4 (48.68 to 77.45)	59.75 (45.69 to 78.12)
Anti-PhtD [Month0] (N=65,50,46,46,45)	4.58 (3.36 to 6.25)	3.83 (2.83 to 5.18)	7.85 (5.18 to 11.9)	6.3 (4.39 to 9.04)	5.49 (3.73 to 8.08)
Anti-PhtD [Month3] (N=74,79,95,91,93)	5.49 (3.97 to 7.59)	4.92 (3.75 to 6.45)	5.14 (4.07 to 6.49)	5.06 (3.96 to 6.47)	5.1 (4.02 to 6.47)
Anti-PhtD [Month8] (N=75,95,98,94,98)	7.77 (5.46 to 11.06)	5.86 (4.51 to 7.62)	9.49 (7.1 to 12.69)	10.01 (7.1 to 14.12)	8.35 (6.22 to 11.21)
Anti-PhtD [Month9] (N=77,94,98,94,97)	9.16 (6.37 to 13.17)	7.32 (5.5 to 9.73)	16.47 (11.34 to 23.94)	14.01 (9.77 to 20.11)	11.71 (8.45 to 16.23)
Anti-PhtD [Month11] (N=77,93,98,93,97)	9.49 (6.86 to 13.14)	7.92 (5.76 to 10.9)	16.93 (11.58 to 24.75)	15.41 (10.83 to 21.94)	15.7 (11.36 to 21.7)
Anti-PhtD [Month14] (N=73,94,98,94,97)	14.06 (9.92 to 19.92)	10.74 (8.01 to 14.4)	19.39 (13.98 to 26.87)	22.04 (16.09 to 30.2)	14.54 (10.62 to 19.92)
Anti-PhtD [Month15] (N=74,93,98,93,98)	15.04 (10.08 to 22.46)	11.35 (8.27 to 15.59)	18.06 (13.04 to 25.02)	24.03 (17.55 to 32.92)	17.07 (12.08 to 24.12)
Anti-PhtD [Month23] (N=73,91,97,92,98)	41.41 (27.82 to 61.62)	29.17 (20.84 to 40.83)	39.84 (28.47 to 55.75)	35.69 (26.26 to 48.5)	35.92 (26.6 to 48.52)

No statistical analyses for this end point

Secondary: 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

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End point title

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

End point description

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 only include results from samples confirmed as positive for Hi/Non Typeable Hi after differentiation from H. haemolyticus by PCR assay. The Total Vaccinated cohort included all subjects with at least one vaccine dose administration documented.

End point type

Secondary

End point timeframe

Up to study end at Month 23 (24-27 months of age)

End point values	HIV+/+ Group	HIV+/- Group	HIV-(3+1) Group	HIV- (3+0) Group	HIV-(2+1) Group
Number of subjects analysed	83	101	100	100	100
Units: Swabs
Any SP – Mth 0 (N=83,101,100,100,100)	23	24	25	30	17
Any SP – Mth 3 (N=81,98,98,95,98)	47	62	58	55	64
Any SP – Mth 8 (N=76,95,98,94,98)	55	61	65	67	67
Any SP – Mth 9 (N=77,96,98,94,98)	50	64	62	66	70
Any SP – Mth 11 (N=77,94,98,94,97)	52	61	67	62	70
Any SP – Mth 14 (N=75,94,98,94,98)	52	64	69	70	70
Any SP – Mth 15 (N=75,94,98,94,98)	59	68	62	70	68
Any SP – Mth 23 (N=73,92,97,92,98)	58	59	63	60	66
Any HI – Mth 0 (N=82,101,99,100,98)	14	12	17	12	12
Any HI – Mth 3 (N=80,98,98,95,98)	30	34	36	33	37
Any HI – Mth 8 (N=77,94,97,94,98)	21	41	34	30	38
Any HI – Mth 9 (N=77,96,97,94,98)	28	47	34	29	32
Any HI – Mth 11 (N=76,93,96,88,92)	33	44	36	34	40
Any HI – Mth 14 (N=68,81,81,73,82)	29	39	38	31	27
Any HI – Mth 15 (N=75,94,98,94,98)	35	54	54	51	55
Any HI – Mth 23 (N=73,92,97,92,98)	39	45	58	53	62
Any MC – Mth 0 (N=83,101,100,100,100)	35	39	42	42	44
Any MC – Mth 3 (N=81,98,98,95,98)	63	88	88	87	90
Any MC – Mth 8 (N=77,95,98,94,98)	56	83	84	79	82
Any MC – Mth 9 (N=77,96,98,94,98)	62	79	75	81	72
Any MC – Mth 11 (N=77,94,98,94,97)	69	80	73	73	83
Any MC – Mth 14 (N=75,94,98,94,98)	65	81	84	90	84
Any MC – Mth 15 (N=75,94,98,94,98)	60	82	83	87	86
Any MC – Mth 23 (N=73,92,97,92,98)	59	73	78	71	79
Any SA – Mth 0 (N=83,101,100,100,100)	37	48	56	57	55
Any SA – Mth 3 (N=81,98,98,95,98)	41	37	37	40	32
Any SA – Mth 8 (N=77,95,98,94,98)	16	18	13	19	24
Any SA – Mth 9 (N=77,96,98,94,98)	19	26	18	16	17
Any SA – Mth 11 (N=77,94,98,94,97)	9	18	13	13	19
Any SA – Mth 14 (N=75,94,98,94,98)	11	15	9	13	13
Any SA – Mth 15 (N=75,94,98,94,98)	12	11	20	13	18
Any SA – Mth 23 (N=73,92,97,92,98)	8	16	10	13	18

No statistical analyses for this end point

Secondary: Number of subjects with acquisition of new Streptococcus pneumoniae and Haemophilus Influenzae strains identified in nasopharyngeal swabs

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End point title

Number of subjects with acquisition of new Streptococcus pneumoniae and Haemophilus Influenzae strains identified in nasopharyngeal swabs

End point description

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 only include results from samples confirmed as positive for Hi/Non Typeable Hi after differentiation from H. haemolyticus by PCR assay. The Total Vaccinated cohort included all subjects with at least one vaccine dose administration documented.

End point type

Secondary

End point timeframe

Up to study end at Month 23 (24-27 months of age)

End point values	HIV+/+ Group	HIV+/- Group	HIV-(3+1) Group	HIV- (3+0) Group	HIV-(2+1) Group
Number of subjects analysed	81	98	98	95	98
Units: Subjects
Any SP – Mth 3 (N=81,98,98,95,98)	35	47	46	41	56
Any SP – Mth 8 (N=77,95,98,94,98)	59	68	70	67	76
Any SP – Mth 9 (N=77,95,98,94,98)	64	76	77	78	82
Any SP – Mth 11 (N=77,93,98,94,97)	69	79	84	84	90
Any SP – Mth 14 (N=75,92,98,94,97)	68	82	90	90	93
Any SP – Mth 15 (N=75,92,98,94,97)	72	86	90	92	94
Any SP – Mth 23 (N=73,90,97,92,97)	72	87	95	90	96
Any HI – Mth 3 (N=80,98,97,95,96)	26	25	27	29	30
Any HI – Mth 8 (N=76,94,96,94,96)	34	49	48	42	45
Any HI – Mth 9 (N=76,94,95,94,96)	45	63	52	52	57
Any HI – Mth 11 (N=75,91,94,88,92)	55	67	60	57	65
Any HI – Mth 14 (N=67,78,78,70,78)	56	60	58	54	59
Any HI – Mth 15 (N=67,78,78,70,78)	59	67	64	58	65
Any HI – Mth 23 (N=65,76,77,69,78)	60	70	71	59	71

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

SAEs: from Month 0 up to Month 23. Unsolicited AEs: within the 31-day post-primary and post Synflorix booster vaccination period. Solicited AEs: During the 4-day period following the primary and the Synflorix booster vaccination.

Adverse event reporting additional description

The occurrence of reported AEs (all/related) was not available and is encoded as equal to the number of subjects affected.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

18.0

Reporting group title

HIV+/+ Group

Reporting group description

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.

Reporting group title

HIV+/- Group

Reporting group description

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.

Reporting group title

HIV- (3+1) Group

Reporting group description

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.

Reporting group title

HIV- (3+0) Group

Reporting group description

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.

Reporting group title

HIV- (2+1) Group

Reporting group description

Serious adverse events	HIV+/+ Group	HIV+/- Group	HIV- (3+1) Group	HIV- (3+0) Group	HIV- (2+1) Group
Total subjects affected by serious adverse events
subjects affected / exposed	31 / 83 (37.35%)	25 / 101 (24.75%)	20 / 100 (20.00%)	15 / 100 (15.00%)	20 / 100 (20.00%)
number of deaths (all causes)	5	4	0	3	0
number of deaths resulting from adverse events	0	0	0	0	0
Injury, poisoning and procedural complications
Herbal toxicity
subjects affected / exposed	0 / 83 (0.00%)	1 / 101 (0.99%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Near drowning
subjects affected / exposed	1 / 83 (1.20%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	1 / 100 (1.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Thermal burn
subjects affected / exposed	0 / 83 (0.00%)	1 / 101 (0.99%)	0 / 100 (0.00%)	2 / 100 (2.00%)	0 / 100 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Burns second degree
subjects affected / exposed	0 / 83 (0.00%)	1 / 101 (0.99%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Electric shock
subjects affected / exposed	0 / 83 (0.00%)	1 / 101 (0.99%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Congenital, familial and genetic disorders
Cerebral palsy
subjects affected / exposed	0 / 83 (0.00%)	1 / 101 (0.99%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Trisomy 21
subjects affected / exposed	0 / 83 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	1 / 100 (1.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ventricular septal defect
subjects affected / exposed	0 / 83 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	1 / 100 (1.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Convulsion
subjects affected / exposed	1 / 83 (1.20%)	1 / 101 (0.99%)	0 / 100 (0.00%)	2 / 100 (2.00%)	0 / 100 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0
Febrile convulsion
subjects affected / exposed	1 / 83 (1.20%)	1 / 101 (0.99%)	3 / 100 (3.00%)	1 / 100 (1.00%)	2 / 100 (2.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	1 / 3	0 / 1	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Encephalitis
subjects affected / exposed	0 / 83 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	1 / 100 (1.00%)	0 / 100 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Encephalopathy
subjects affected / exposed	0 / 83 (0.00%)	1 / 101 (0.99%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	1 / 83 (1.20%)	1 / 101 (0.99%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
Iron deficiency anaemia
subjects affected / exposed	1 / 83 (1.20%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Death
subjects affected / exposed	1 / 83 (1.20%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
Sudden death
subjects affected / exposed	2 / 83 (2.41%)	0 / 101 (0.00%)	0 / 100 (0.00%)	1 / 100 (1.00%)	0 / 100 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 2	0 / 0	0 / 0	1 / 1	0 / 0
Sudden infant death syndrome
subjects affected / exposed	0 / 83 (0.00%)	1 / 101 (0.99%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	0 / 83 (0.00%)	1 / 101 (0.99%)	1 / 100 (1.00%)	0 / 100 (0.00%)	1 / 100 (1.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
Vomiting
subjects affected / exposed	1 / 83 (1.20%)	0 / 101 (0.00%)	1 / 100 (1.00%)	0 / 100 (0.00%)	1 / 100 (1.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Food poisoning
subjects affected / exposed	0 / 83 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	1 / 100 (1.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Hepatitis neonatal
subjects affected / exposed	1 / 83 (1.20%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Atelectasis
subjects affected / exposed	1 / 83 (1.20%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bronchospasm
subjects affected / exposed	1 / 83 (1.20%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia aspiration
subjects affected / exposed	0 / 83 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	2 / 100 (2.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Asthma
subjects affected / exposed	0 / 83 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	1 / 100 (1.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Renal impairment
subjects affected / exposed	1 / 83 (1.20%)	1 / 101 (0.99%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
Infections and infestations
AIDS dementia complex
subjects affected / exposed	1 / 83 (1.20%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bronchitis
subjects affected / exposed	1 / 83 (1.20%)	1 / 101 (0.99%)	1 / 100 (1.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bronchopneumonia
subjects affected / exposed	13 / 83 (15.66%)	5 / 101 (4.95%)	6 / 100 (6.00%)	1 / 100 (1.00%)	8 / 100 (8.00%)
occurrences causally related to treatment / all	0 / 13	0 / 5	0 / 6	0 / 1	0 / 8
deaths causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0
Croup infectious
subjects affected / exposed	0 / 83 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	1 / 100 (1.00%)	0 / 100 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
Cytomegalovirus infection
subjects affected / exposed	2 / 83 (2.41%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	8 / 83 (9.64%)	8 / 101 (7.92%)	5 / 100 (5.00%)	4 / 100 (4.00%)	4 / 100 (4.00%)
occurrences causally related to treatment / all	1 / 8	0 / 8	0 / 5	0 / 4	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
H1N1 influenza
subjects affected / exposed	0 / 83 (0.00%)	0 / 101 (0.00%)	1 / 100 (1.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lower respiratory tract infection
subjects affected / exposed	0 / 83 (0.00%)	1 / 101 (0.99%)	0 / 100 (0.00%)	1 / 100 (1.00%)	1 / 100 (1.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Measles
subjects affected / exposed	1 / 83 (1.20%)	2 / 101 (1.98%)	0 / 100 (0.00%)	1 / 100 (1.00%)	1 / 100 (1.00%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
Meningitis meningococcal
subjects affected / exposed	1 / 83 (1.20%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Meningitis tuberculous
subjects affected / exposed	0 / 83 (0.00%)	0 / 101 (0.00%)	1 / 100 (1.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Oral candidiasis
subjects affected / exposed	1 / 83 (1.20%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumococcal sepsis
subjects affected / exposed	1 / 83 (1.20%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumocystis jiroveci pneumonia
subjects affected / exposed	4 / 83 (4.82%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)
occurrences causally related to treatment / all	0 / 4	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	1 / 83 (1.20%)	1 / 101 (0.99%)	3 / 100 (3.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia staphylococcal
subjects affected / exposed	1 / 83 (1.20%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary tuberculosis
subjects affected / exposed	11 / 83 (13.25%)	1 / 101 (0.99%)	1 / 100 (1.00%)	1 / 100 (1.00%)	1 / 100 (1.00%)
occurrences causally related to treatment / all	0 / 11	0 / 1	0 / 1	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Rectal abscess
subjects affected / exposed	0 / 83 (0.00%)	0 / 101 (0.00%)	1 / 100 (1.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Streptococcal sepsis
subjects affected / exposed	0 / 83 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	1 / 100 (1.00%)	0 / 100 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Tuberculosis
subjects affected / exposed	1 / 83 (1.20%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Upper respiratory tract infection
subjects affected / exposed	1 / 83 (1.20%)	3 / 101 (2.97%)	1 / 100 (1.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 3	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	1 / 83 (1.20%)	3 / 101 (2.97%)	1 / 100 (1.00%)	0 / 100 (0.00%)	1 / 100 (1.00%)
occurrences causally related to treatment / all	0 / 1	0 / 3	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bronchiolitis
subjects affected / exposed	1 / 83 (1.20%)	3 / 101 (2.97%)	4 / 100 (4.00%)	1 / 100 (1.00%)	1 / 100 (1.00%)
occurrences causally related to treatment / all	0 / 1	0 / 3	0 / 4	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis rotavirus
subjects affected / exposed	0 / 83 (0.00%)	1 / 101 (0.99%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Abscess limb
subjects affected / exposed	1 / 83 (1.20%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Arthritis bacterial
subjects affected / exposed	1 / 83 (1.20%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
HIV infection
subjects affected / exposed	0 / 83 (0.00%)	0 / 101 (0.00%)	1 / 100 (1.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injection site abscess
subjects affected / exposed	0 / 83 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	1 / 100 (1.00%)	0 / 100 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lobar pneumonia
subjects affected / exposed	0 / 83 (0.00%)	1 / 101 (0.99%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Oral herpes
subjects affected / exposed	0 / 83 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	1 / 100 (1.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Otitis media
subjects affected / exposed	0 / 83 (0.00%)	1 / 101 (0.99%)	1 / 100 (1.00%)	0 / 100 (0.00%)	1 / 100 (1.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pyelonephritis
subjects affected / exposed	1 / 83 (1.20%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Subacute endocarditis
subjects affected / exposed	0 / 83 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	1 / 100 (1.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Tonsillitis
subjects affected / exposed	1 / 83 (1.20%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	2 / 100 (2.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Kwashiorkor
subjects affected / exposed	2 / 83 (2.41%)	1 / 101 (0.99%)	0 / 100 (0.00%)	1 / 100 (1.00%)	0 / 100 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
Marasmus
subjects affected / exposed	1 / 83 (1.20%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypokalaemia
subjects affected / exposed	0 / 83 (0.00%)	1 / 101 (0.99%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	HIV+/+ Group	HIV+/- Group	HIV- (3+1) Group	HIV- (3+0) Group	HIV- (2+1) Group
Total subjects affected by non serious adverse events
subjects affected / exposed	83 / 83 (100.00%)	100 / 101 (99.01%)	98 / 100 (98.00%)	98 / 100 (98.00%)	98 / 100 (98.00%)
General disorders and administration site conditions
Diarrhoea (unsolicited post-primary)
alternative assessment type: Systematic
subjects affected / exposed ^[1]	13 / 83 (15.66%)	16 / 101 (15.84%)	18 / 98 (18.37%)	10 / 98 (10.20%)	5 / 98 (5.10%)
occurrences all number	13	16	18	10	5
Drowsiness (post-primary)
alternative assessment type: Systematic
subjects affected / exposed ^[2]	49 / 83 (59.04%)	62 / 101 (61.39%)	70 / 98 (71.43%)	70 / 98 (71.43%)	68 / 98 (69.39%)
occurrences all number	49	62	70	70	68
Drowsiness (post-booster)
alternative assessment type: Systematic
subjects affected / exposed ^[3]	17 / 74 (22.97%)	28 / 95 (29.47%)	34 / 96 (35.42%)	0 / 100 (0.00%)	33 / 96 (34.38%)
occurrences all number	17	28	34	0	33
Fever (post-primary)
alternative assessment type: Systematic
subjects affected / exposed ^[4]	38 / 83 (45.78%)	36 / 101 (35.64%)	41 / 98 (41.84%)	28 / 98 (28.57%)	28 / 98 (28.57%)
occurrences all number	38	36	41	28	28
Fever (post-booster)
alternative assessment type: Systematic
subjects affected / exposed ^[5]	9 / 74 (12.16%)	11 / 95 (11.58%)	7 / 96 (7.29%)	0 / 100 (0.00%)	11 / 96 (11.46%)
occurrences all number	9	11	7	0	11
Irritability (post-primary)
alternative assessment type: Systematic
subjects affected / exposed ^[6]	63 / 83 (75.90%)	84 / 101 (83.17%)	89 / 98 (90.82%)	89 / 98 (90.82%)	91 / 98 (92.86%)
occurrences all number	63	84	89	89	91
Irritability (post-booster)
alternative assessment type: Systematic
subjects affected / exposed ^[7]	25 / 74 (33.78%)	35 / 95 (36.84%)	31 / 96 (32.29%)	0 / 100 (0.00%)	43 / 96 (44.79%)
occurrences all number	25	35	31	0	43
Decreased appetite (post-primary)
alternative assessment type: Systematic
subjects affected / exposed ^[8]	36 / 83 (43.37%)	53 / 101 (52.48%)	56 / 98 (57.14%)	57 / 98 (58.16%)	62 / 98 (63.27%)
occurrences all number	36	53	56	57	62
Decreased appetite (post-booster)
alternative assessment type: Systematic
subjects affected / exposed ^[9]	17 / 74 (22.97%)	23 / 95 (24.21%)	29 / 96 (30.21%)	0 / 100 (0.00%)	37 / 96 (38.54%)
occurrences all number	17	23	29	0	37
Pain (post-primary)
alternative assessment type: Systematic
subjects affected / exposed ^[10]	73 / 83 (87.95%)	93 / 101 (92.08%)	92 / 98 (93.88%)	95 / 98 (96.94%)	97 / 98 (98.98%)
occurrences all number	73	93	92	95	97
Pain (post-booster)
alternative assessment type: Systematic
subjects affected / exposed ^[11]	40 / 74 (54.05%)	58 / 95 (61.05%)	62 / 96 (64.58%)	0 / 100 (0.00%)	60 / 96 (62.50%)
occurrences all number	40	58	62	0	60
Redness (post-primary)
alternative assessment type: Systematic
subjects affected / exposed ^[12]	62 / 83 (74.70%)	80 / 101 (79.21%)	83 / 98 (84.69%)	83 / 98 (84.69%)	84 / 98 (85.71%)
occurrences all number	62	80	83	83	84
Redness (post-booster)
alternative assessment type: Systematic
subjects affected / exposed ^[13]	25 / 74 (33.78%)	31 / 95 (32.63%)	39 / 96 (40.63%)	0 / 100 (0.00%)	45 / 96 (46.88%)
occurrences all number	25	31	39	0	45
Swelling (post-primary)
alternative assessment type: Systematic
subjects affected / exposed ^[14]	67 / 83 (80.72%)	83 / 101 (82.18%)	84 / 98 (85.71%)	91 / 98 (92.86%)	84 / 98 (85.71%)
occurrences all number	67	83	84	91	84
Swelling (post-booster)
alternative assessment type: Systematic
subjects affected / exposed ^[15]	28 / 74 (37.84%)	39 / 95 (41.05%)	38 / 96 (39.58%)	0 / 100 (0.00%)	53 / 96 (55.21%)
occurrences all number	28	39	38	0	53
Vomiting (post-primary)
alternative assessment type: Systematic
subjects affected / exposed ^[16]	17 / 83 (20.48%)	19 / 101 (18.81%)	15 / 98 (15.31%)	18 / 98 (18.37%)	23 / 98 (23.47%)
occurrences all number	17	19	15	18	23
Pyrexia (unsolicited post-primary)
subjects affected / exposed	5 / 83 (6.02%)	8 / 101 (7.92%)	5 / 100 (5.00%)	9 / 100 (9.00%)	9 / 100 (9.00%)
occurrences all number	5	8	5	9	9
Eye disorders
Eye discharge (unsolicited post-primary)
subjects affected / exposed	4 / 83 (4.82%)	6 / 101 (5.94%)	6 / 100 (6.00%)	4 / 100 (4.00%)	3 / 100 (3.00%)
occurrences all number	4	6	6	4	3
Gastrointestinal disorders
Diarrhoea (unsolicited post-primary)
subjects affected / exposed	13 / 83 (15.66%)	16 / 101 (15.84%)	18 / 100 (18.00%)	13 / 100 (13.00%)	11 / 100 (11.00%)
occurrences all number	13	16	18	13	11
Diarrhoea (post-booster)
subjects affected / exposed ^[17]	5 / 76 (6.58%)	10 / 96 (10.42%)	10 / 98 (10.20%)	0 / 100 (0.00%)	8 / 98 (8.16%)
occurrences all number	5	10	10	0	8
Vomiting (unsolicited post-primary)
subjects affected / exposed	18 / 83 (21.69%)	16 / 101 (15.84%)	11 / 100 (11.00%)	15 / 100 (15.00%)	12 / 100 (12.00%)
occurrences all number	18	16	11	15	12
Vomiting (unsolicited post-booster)
subjects affected / exposed ^[18]	1 / 76 (1.32%)	8 / 96 (8.33%)	7 / 98 (7.14%)	0 / 100 (0.00%)	5 / 98 (5.10%)
occurrences all number	1	8	7	0	5
Abdominal pain upper (unsolicited post-primary)
subjects affected / exposed	4 / 83 (4.82%)	1 / 101 (0.99%)	4 / 100 (4.00%)	3 / 100 (3.00%)	9 / 100 (9.00%)
occurrences all number	4	1	4	3	9
Constipation (unsolicited post-primary)
subjects affected / exposed	0 / 83 (0.00%)	3 / 101 (2.97%)	3 / 100 (3.00%)	5 / 100 (5.00%)	6 / 100 (6.00%)
occurrences all number	0	3	3	5	6
Respiratory, thoracic and mediastinal disorders
Cough (unsolicited post-primary)
subjects affected / exposed	35 / 83 (42.17%)	73 / 101 (72.28%)	67 / 100 (67.00%)	58 / 100 (58.00%)	66 / 100 (66.00%)
occurrences all number	35	73	67	58	66
Cough (unsolicited post-booster)
subjects affected / exposed ^[19]	17 / 76 (22.37%)	23 / 96 (23.96%)	24 / 98 (24.49%)	0 / 100 (0.00%)	13 / 98 (13.27%)
occurrences all number	17	23	24	0	13
Nasal Obstruction (unsolicited post-primary)
subjects affected / exposed	29 / 83 (34.94%)	40 / 101 (39.60%)	50 / 100 (50.00%)	49 / 100 (49.00%)	51 / 100 (51.00%)
occurrences all number	29	40	50	49	51
Nasal Obstruction (unsolicited post-booster)
subjects affected / exposed ^[20]	7 / 76 (9.21%)	4 / 96 (4.17%)	6 / 98 (6.12%)	0 / 100 (0.00%)	6 / 98 (6.12%)
occurrences all number	7	4	6	0	6
Rhinorrhoea (unsolicited post-booster)
subjects affected / exposed ^[21]	1 / 76 (1.32%)	5 / 96 (5.21%)	7 / 98 (7.14%)	0 / 100 (0.00%)	5 / 98 (5.10%)
occurrences all number	1	5	7	0	5
Rhinorrhoea (unsolicited post-primary)
subjects affected / exposed	3 / 83 (3.61%)	9 / 101 (8.91%)	10 / 100 (10.00%)	9 / 100 (9.00%)	10 / 100 (10.00%)
occurrences all number	3	9	10	9	10
Sneezing (unsolicited post-primary)
subjects affected / exposed	0 / 83 (0.00%)	9 / 101 (8.91%)	11 / 100 (11.00%)	6 / 100 (6.00%)	9 / 100 (9.00%)
occurrences all number	0	9	11	6	9
Skin and subcutaneous tissue disorders
Eczema (unsolicited post-booster)
subjects affected / exposed	9 / 83 (10.84%)	12 / 101 (11.88%)	11 / 100 (11.00%)	12 / 100 (12.00%)	14 / 100 (14.00%)
occurrences all number	9	12	11	12	14
Rash (unsolicited post-primary)
subjects affected / exposed	26 / 83 (31.33%)	25 / 101 (24.75%)	16 / 100 (16.00%)	28 / 100 (28.00%)	21 / 100 (21.00%)
occurrences all number	26	25	16	28	21
Rash (unsolicited post-booster)
subjects affected / exposed ^[22]	4 / 76 (5.26%)	4 / 96 (4.17%)	3 / 98 (3.06%)	0 / 100 (0.00%)	5 / 98 (5.10%)
occurrences all number	4	4	3	0	5
Dermatitis diaper (unsolicited post-primary)
subjects affected / exposed	12 / 83 (14.46%)	8 / 101 (7.92%)	11 / 100 (11.00%)	8 / 100 (8.00%)	4 / 100 (4.00%)
occurrences all number	12	8	11	8	4
Infections and infestations
Upper respiratory tract infection (unsolicited post-primary)
subjects affected / exposed	4 / 83 (4.82%)	13 / 101 (12.87%)	13 / 100 (13.00%)	11 / 100 (11.00%)	12 / 100 (12.00%)
occurrences all number	4	13	13	11	12
Upper respiratory tract infection (unsolicited post-booster)
subjects affected / exposed ^[23]	2 / 76 (2.63%)	5 / 96 (5.21%)	6 / 98 (6.12%)	0 / 100 (0.00%)	5 / 98 (5.10%)
occurrences all number	2	5	6	0	5
Bronchiolitis (unsolicited post-primary)
subjects affected / exposed	1 / 83 (1.20%)	6 / 101 (5.94%)	3 / 100 (3.00%)	8 / 100 (8.00%)	2 / 100 (2.00%)
occurrences all number	1	6	3	8	2
Bronchopneumonia (unsolicited post-primary)
subjects affected / exposed	5 / 83 (6.02%)	3 / 101 (2.97%)	3 / 100 (3.00%)	0 / 100 (0.00%)	2 / 100 (2.00%)
occurrences all number	5	3	3	0	2
Oral candidiasis (unsolicited post-primary)
subjects affected / exposed	9 / 83 (10.84%)	4 / 101 (3.96%)	6 / 100 (6.00%)	3 / 100 (3.00%)	3 / 100 (3.00%)
occurrences all number	9	4	6	3	3
Metabolism and nutrition disorders
Decreased appetite (unsolicited post-booster)
subjects affected / exposed ^[24]	4 / 76 (5.26%)	6 / 96 (6.25%)	4 / 98 (4.08%)	0 / 100 (0.00%)	4 / 98 (4.08%)
occurrences all number	4	6	4	0	4
Decreased appetite (unsolicited post-primary)
subjects affected / exposed	6 / 83 (7.23%)	9 / 101 (8.91%)	1 / 100 (1.00%)	3 / 100 (3.00%)	3 / 100 (3.00%)
occurrences all number	6	9	1	3	3

Notes
[1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was performed solely on subjects with their symptom sheets completed.
[2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was performed solely on subjects with their symptom sheets completed.
[3] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was performed solely on subjects with their symptom sheets completed.
[4] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was performed solely on subjects with their symptom sheets completed.
[5] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was performed solely on subjects with their symptom sheets completed.
[6] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was performed solely on subjects with their symptom sheets completed.
[7] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was performed solely on subjects with their symptom sheets completed.
[8] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was performed solely on subjects with their symptom sheets completed.
[9] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was performed solely on subjects with their symptom sheets completed.
[10] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was performed solely on subjects with their symptom sheets completed.
[11] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was performed solely on subjects with their symptom sheets completed.
[12] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was performed solely on subjects with their symptom sheets completed.
[13] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was performed solely on subjects with their symptom sheets completed.
[14] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was performed solely on subjects with their symptom sheets completed.
[15] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was performed solely on subjects with their symptom sheets completed.
[16] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was performed solely on subjects with their symptom sheets completed.
[17] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was performed solely on subjects with their symptom sheets completed.
[18] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was performed solely on subjects with their symptom sheets completed.
[19] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was performed solely on subjects with their symptom sheets completed.
[20] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was performed solely on subjects with their symptom sheets completed.
[21] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was performed solely on subjects with their symptom sheets completed.
[22] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was performed solely on subjects with their symptom sheets completed.
[23] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was performed solely on subjects with their symptom sheets completed.
[24] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was performed solely on subjects with their symptom sheets completed.

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Were there any global substantial amendments to the protocol? Yes

09 Dec 2008

• Introduction of Prevenar in the national recommended vaccination program of South Africa as from April 2009. • Decision to consider rotavirus vaccine as study vaccine due to its anticipated introduction into the national vaccination program during 2009. • Addition of a rationale for including HIV exposed uninfected children in the study.

29 Jun 2009

• Decision to test immunogenicity of the oral poliovirus vaccine (OPV) on request of local authorities. • Permission for inclusion of HIV infected infants with weight for age < 3rd percentile at Visit 1, using standard growth charts, at the discretion of the investigator.

24 Feb 2010

As a slow enrolment rate of HIV+/+ subjects was observed, it was decided to extend the recruitment time by approximately 6 months in Amendment 3 in order to increase the chance to reach target enrolment in the HIV+/+ study group.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

The study aimed to enrol 100 HIV +/+ subjects but succeed to enrol 83 mainly due to decrease of vertical HIV transmission in South Africa. Some subjects HIV + at screening, tested negative at subsequent HIV testing, were reallocated in HIV+/-Group.

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Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of Subjects With Anti-pneumococcal Vaccine Serotype Antibody Concentrations Equal to or Above 0.20 Microgram Per Millilitre (µg/mL)

Primary: Number of Subjects With Anti-pneumococcal Vaccine Serotype Antibody Concentrations Equal to or Above 0.20 Microgram Per Millilitre (µg/mL)

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

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

Secondary: Number of Subjects with Any, Severe (Grade 3) and Related Solicited General Adverse Events (AEs)

Secondary: Number of Subjects with Any, Severe (Grade 3) and Related Solicited General Adverse Events (AEs)

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

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

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

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

Secondary: Number of Subjects With Unsolicited AEs

Secondary: Number of Subjects With Unsolicited AEs

Secondary: Number of Subjects With Unsolicited AEs

Secondary: Number of Subjects With Unsolicited AEs

Secondary: Number of Subjects With Serious Adverse Events (SAEs)

Secondary: Number of Subjects With Serious Adverse Events (SAEs)

Secondary: Concentrations of antibodies against Vaccine Pneumococcal Serotypes

Secondary: Concentrations of antibodies against Vaccine Pneumococcal Serotypes

Secondary: Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes

Secondary: Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes

Secondary: Opsonophagocytic Titers against Vaccine Pneumococcal Serotypes

Secondary: Opsonophagocytic Titers against Vaccine Pneumococcal Serotypes

Secondary: Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes

Secondary: Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes

Secondary: Concentrations of Antibodies against Cross-reactive Pneumococcal Serotypes 6A and 19A

Secondary: Concentrations of Antibodies against Cross-reactive Pneumococcal Serotypes 6A and 19A

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

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

Secondary: Opsonophagocytic Titers against Cross-reactive Pneumococcal Serotypes 6A and 19A

Secondary: Opsonophagocytic Titers against Cross-reactive Pneumococcal Serotypes 6A and 19A

Secondary: Opsonophagocytic Titers against Cross-reactive Pneumococcal Serotypes 6A and 19A

Secondary: Opsonophagocytic Titers against Cross-reactive Pneumococcal Serotypes 6A and 19A

Secondary: Concentrations of Antibodies Against Protein D (PD) by ELISA

Secondary: Concentrations of Antibodies Against Protein D (PD) by ELISA

Secondary: Concentrations of Antibodies Against Protein D (PD) by ELISA

Secondary: Concentrations of Antibodies Against Protein D (PD) by ELISA

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

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

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

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

Secondary: Concentrations of Antibodies Against Bordetella Pertussis (BPT) by ELISA

Secondary: Concentrations of Antibodies Against Bordetella Pertussis (BPT) by ELISA

Secondary: Concentrations of Antibodies Against Bordetella Pertussis (BPT) by ELISA

Secondary: Concentrations of Antibodies Against Bordetella Pertussis (BPT) by ELISA

Secondary: Concentrations of Antibodies against Polyribosyl-ribitol Phosphate (PRP)

Secondary: Concentrations of Antibodies against Polyribosyl-ribitol Phosphate (PRP)

Secondary: Concentrations of Antibodies against Polyribosyl-ribitol Phosphate (PRP)

Secondary: Concentrations of Antibodies against Polyribosyl-ribitol Phosphate (PRP)

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

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

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

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

Secondary: Concentrations of Antibodies against Rotavirus Immunoglobulin A (Rotavirus IgA), by Rotarix Vaccination Status

Secondary: Concentrations of Antibodies against Rotavirus Immunoglobulin A (Rotavirus IgA), by Rotarix Vaccination Status

Secondary: Concentrations of Antibodies Against Measles

Secondary: Concentrations of Antibodies Against Measles

Secondary: Anti-LytC IgA and Anti-PhtD IgA antibodies concentrations in salivary samples

Secondary: Anti-LytC IgA and Anti-PhtD IgA antibodies concentrations in salivary samples

Secondary: 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

Secondary: 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

Secondary: Number of subjects with acquisition of new Streptococcus pneumoniae and Haemophilus Influenzae strains identified in nasopharyngeal swabs

Secondary: Number of subjects with acquisition of new Streptococcus pneumoniae and Haemophilus Influenzae strains identified in nasopharyngeal swabs

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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