The study listed may include approved and non-approved uses, formulations or treatment regimens. The results reported in any single study may not reflect the overall results obtained on studies of a product. Before prescribing any product mentioned in this Register, healthcare professionals should consult prescribing information for the product approved in their country. Study No.: 111634 (10PN-PD-DIT-034 PRI & BST) Title: Primary and booster vaccination course in human immunodeficiency virus (HIV) infected infants, HIV exposed uninfected infants and unexposed uninfected infants receiving the pneumococcal vaccine GSK 1024850A. Synflorix - GSK1024850A (10Pn): GlaxoSmithKline (GSK) Biologicals' 10-valent pneumococcal polysaccharide and non-typable Haemophilus influenzae protein D conjugate vaccine. Rationale: The purpose of this study was to evaluate the immunogenicity and safety of 10Pn vaccine in HIV infected infants (HIV+/+), HIV exposed uninfected infants (HIV+/-) and HIV unexposed uninfected infants (HIV-) when given as a 3-dose primary vaccination at 6, 10 and 14 weeks of age. In addition, the study assessed persistence of 10Pn antibodies after primary and after booster vaccination as well as the immunogenicity and safety of the vaccine one month after booster dose (9-10 months of age), which corresponds to the age of the first measles vaccine administration in most developing countries. Finally this study aimed to assess the prevalence of nasopharyngeal carriage of Streptococcus pneumoniae (S.pneumoniae) and Haemophilus influenzae (H.influenzae) up to 24 months of age in all study participants. Subjects also received 3 primary and one booster dose of Tritanrix - HepB/Hib (vaccination against diphtheria, tetanus, whole-cell Bordetella pertussis, hepatitis B and Haemophilus influenzae type b diseases that is recommended by the World Health Organisation (WHO) Expanded Program on Immunization (EPI));. And a 2-dose vaccination against rotavirus disease (Rotarix ). During the course of the study, some subjects who were HIV positive at screening were tested seronegative at subsequent HIV testing. Consequently, these subjects were reallocated from HIV+/+ group to the group of HIV exposed uninfected subjects (HIV+/-) for final study analysis.therefore the results presented in the previously disclosed summary for this study, which included immunogenicity and safety results from study start up to approximately 1 month after 10Pn booster vaccination have been replaced by the results of final analysis. Tritanrix -HepB/Hib (DTPw-HBV/Hib): GSK Biologicals' diphtheria, tetanus, pertussis, hepatitis B and Haemophilus influenzae type b vaccine. Rotarix (HRV): GSK Biologicals oral live attenuated human rotavirus vaccine. Phase: III Study Period: 17 February 2009 to 27 June 2012 Study Design: Single-centre, open, partially* randomised, controlled study with 5 parallel groups. *HIV unexposed uninfected infants were randomised into 3 sub-groups (1:1:1) to receive different 10Pn vaccination schedule (see Treatment Section below). Centres: 1 centre in South Africa Indication: Immunisation of infants against S. pneumoniae diphtheria, tetanus, pertussis, hepatitis B, H. influenzae type b, rotavirus diseases. Treatment: The study included 3 populations defined based on the HIV status of both the mother and the infant: - Infants born from a HIV positive mother and confirmed as being HIV infected, as documented by a positive HIV deoxyribonucleic acid polymerase chain reaction (HIV DNA-PCR) at screening and by a positive HIV viral load test at Month 0, were referred as HIV +/+. - Infants born from a HIV positive mother and confirmed as being HIV exposed uninfected, as documented by a negative HIV DNA-PCR result at screening, were referred as HIV +/-. - Infants born from a HIV negative mother* and confirmed as HIV unexposed uninfected, as documented by a negative HIV enzyme-linked immunosorbent assay (ELISA) result at Month 0, were referred as HIV *As documented by both a negative HIV ELISA test performed on blood from the mother after 24 weeks of gestational age and the absence of clinical signs of an acute seroconversion syndrome thereafter until delivery. The study included 5 parallel groups as follows: HIV+/+ : Subjects received 3 primary doses (at 6, 10 & 14 weeks of age) and 1 booster dose of 10Pn vaccine (at 9 months of age). HIV+/- : Subjects received 3 primary doses (at 6, 10 & 14 weeks of age) and 1 booster dose of 10Pn vaccine (at 9 months of age). HIV- : Subjects were randomized into 3 sub-groups; HIV- (3+1) Subjects received 3 primary doses (at 6, 10 & 14 weeks of age) and 1 booster dose of 10Pn vaccine (at 9 months of age). HIV- (3+0) : Subjects received 3 primary doses of 10Pn vaccine (at 6, 10 & 14 weeks of age). HIV- (2+1) : Subjects received 2 primary doses (at 6 & 14 weeks of age) and 1 booster dose of 10Pn
vaccine (at 9 months of age). Note: - For some analyses, HIV- (3+1) and HIV- (3+0) were pooled [HIV- (3+1) + HIV- (3+0) ]. - Subjects in all groups received 3 primary vaccine doses (at 6, 10 & 14 weeks of age) and 1 booster vaccine dose (at 15-18 months of age) of DTPw-HBV/Hib, 2 vaccine doses of HRV (at 10 & 14 weeks of age), and 2 doses of measles $ vaccine (9-10 months of age & 15-18 months of age). $ Measles vaccine was not considered as a study vaccine. The 10Pn vaccine was administered intramuscularly (IM) in the right thigh, the DTPw-HBV/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. HRV was given orally. Objectives: To evaluate and characterize the immune response to 10Pn vaccine 1 month following a 3-dose (6, 10 and 14 weeks of age) primary vaccination course in HIV+/+ infants, HIV+/- infants and HIV- infants. Primary Outcome/Efficacy Variable: Immunogenicity Anti-pneumococcal vaccine serotype antibody concentrations 0.20 g/ml, 1 month after primary immunization. Secondary Outcome/Efficacy Variable(s): Immunogenicity Concentration of antibodies and opsonophagocytic titres against components of the investigational 10Pn vaccine, 1 month following primary and booster vaccination up to study end. - Concentrations of antibodies and opsonophagocytic activity against vaccine pneumococcal serotypes. - Concentrations of antibodies and opsonophagocytic activity against cross-reactive pneumococcal serotypes 6A and 19A. - Concentrations of antibodies against protein D. Concentration of antibodies against components of the co-administered DTPw-HBV/Hib vaccine, 1 month after primary and booster vaccination. - Antibody concentrations against diphtheria toxoid (DT), tetanus toxoid (TT), B. pertussis, hepatitis B surface antigen (HBs) and polyribosyl-ribitol phosphate (PRP). Concentration of antibodies induced by the co-administered HRV vaccine, 1 month after the administration of the second vaccine dose. - Anti-rotavirus IgA antibody concentration. Titres against the co-administered measles vaccine, 1 month following administration of the 1 st and 2 nd vaccine dose. - Titres against measles. Salivary antibodies - Salivary antibodies against selected common bacterial protein antigens. Carriage Prevalence of H. influenzae and/or S. pneumoniae (vaccine serotypes, cross-reactive or other serotypes) and other bacterial pathogens in the nasopharynx. Acquisition of new S. pneumoniae and/or H. influenzae strains. Safety Occurrence of each solicited adverse event within 4 days after each vaccination. - Local (any, grade 3) adverse events (AEs). - General (any, grade 3, related) AEs. Occurrence of unsolicited AEs within 31 days after each vaccination. Occurrence of serious adverse events (SAEs) following screening or after the first vaccination, as applicable, up to study end. Statistical Methods: The analyses were performed on the Total Vaccinated cohort, the According-To-Protocol (ATP) cohort for immunogenicity and the ATP cohort for immunogenicity at 15-18 months. - The Total Vaccinated cohort included all subjects with at least one vaccine dose administration documented. - The ATP cohort for immunogenicity included all evaluable subjects (i.e. those meeting all eligibility criteria, complying with the procedures and intervals defined in the protocol, with no elimination criteria during the study) 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. - The ATP cohort for immunogenicity at 15-18 months included all evaluable subjects form 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 the booster dose. Analysis of Immunogenicity The analysis was performed on the ATP cohort for immunogenicity and the ATP cohort for immunogenicity at 15-18 months. For each group, at each time point a blood sample result was available; Antibody Geometric Mean Concentrations/Titres (GMCs/GMTs) with 95% Confidence Intervals (CIs) were tabulated for immune responses against each serotype/antigen. Seropositivity rate and seroprotection rate (SPR) and booster vaccine response with exact 95% CIs were calculated for each appropriate serotype/antigen. Percentage of subjects with pneumococcal antibody concentrations (22F-inhibition ELISA) 0.20 g/ml with exact 95% CIs was calculated for each pneumococcal serotype. The immune response to pneumococcal vaccine as measured by Opsonophagocytic activity was also tabulated for each pneumococcal serotype The post-primary immunogenicity analysis (up to the pre-booster time point) was also done for the pooled HIV- groups [HIV- (3+1) + HIV- (3+0) ]. Additionally, salivary samples were analysed to explore the natural immune response of salivary antibodies (such as LytC IgA and PhtD IgA antibodies) to selected common bacterial protein antigens. Percentage of positives samples and GMCs were also tabulated. A seronegative subject was a subject whose concentration/titre was below the assay cut-off value. A seropositive subject was defined as a subject whose concentration/titre was greater than or equal to the assay cut-off value for the following antigens: - Anti-pneumococcal serotypes 1, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F antibody concentrations 0.05 µg/ml. - Opsonophagocytic activity against pneumococcal serotypes 1, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F 8. - Anti-PD antibody concentration 100 EL.U/mL. - Anti-Bordetella pertussis (BPT) antibody concentration 15 EL.U/mL. - Anti-measles antibody concentration 150 miu/ml. - Anti-rotavirus Immunoglobulin A (IgA) antibody concentration 20 U/mL. A seroprotected subject was defined as a subject whose concentration was greater than or equal to the assay cut-off defined as seroprotective level: - Anti-diphtheria and anti-tetanus toxoid antibody concentration 0.1 IU/mL. - Anti-PRP antibody concentration 0.15 µg/ml and 1.0 µg/ml. - Anti-HBs antibody concentration 10 miu/ml. Note: 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 tables showed updated results following partial or complete retesting/reanalysis. The retest had been performed in using Food and Drug Administration (FDA)-approved ChemiLuminescence ImmunoAssay (CLIA) commercial assay Centaur. Analysis of Carriage Positive cultures of H. influenzae and S. pneumoniae and other bacterial pathogens (such as Moraxella catarrhalis and Staphylococcus aureus) identified in the nasopharynx were analyzed for the Total Vaccinated cohort. Percentage of subjects with positive nasopharyngeal sample was tabulated per group, at each swab time point. Acquisition of new S. pneumoniae and/or H. influenzae strains in the nasopharynx was tabulated per group, at each swab time point. Analysis of Safety The analysis was performed on the Total Vaccinated cohort. The incidence of each individual solicited local and general symptom reported during the 4-day (Days 0-3) post-primary and post-booster vaccination (with 10Pn vaccine) follow-up period was calculated for each vaccine dose (and across doses for the primary vaccination), with exact 95% CIs. The same tabulation was performed for Grade 3 solicited symptoms and general solicited symptoms assessed by the investigator as causally related to the vaccination. The proportion of subjects with at least 1 unsolicited AE within the 31-Day (Days 0-30) post-primary vaccination follow-up period and post-booster vaccination with 10Pn vaccine was tabulated per group according to the Medical Dictionary for Regulatory Activities (MedDRA) preferred terms. SAEs occurring from study start up to study end, were also tabulated
according to MedDRA preferred term as well as the SAEs assessed by the investigators as related to the vaccination.. Study Population: Male or female subjects between, and including 6-10 weeks (42-76 days) of age at the time of the first vaccination were included in the study, who had no history of or previous vaccination against n against diphtheria, tetanus, pertussis, Haemophilus influenzae type b, rotavirus and Streptococcus pneumoniae. For HIV+/+, infants with stages III and IV of HIV, according to latest version of the WHO classification were excluded from the study. Also, babies whose weight for age was < 3 rd percentile at Month 0, using standard growth charts, with the exception of HIV+/+ infants were excluded from the study. Written informed consent was obtained from the parent(s)/guardian(s) of the child. Number of subjects HIV+/+ HIV+/- HIV- (3+1) HIV- (3+0) HIV- (2+1) Planned, N 100 100 100 100 100 Randomized, N (Total Vaccinated cohort) 83 101 100 100 100 Completed up to Month 9, n (%) 77 (92.8) 96 (95.0) 98 (98.0) 94 (94.0) 98 (98.0) Completed up to Month 23, n (%) 73 (88.0) 92 (91.1) 97 (97.0) 92 (92.0) 98 (98.0) Total Number Subjects Withdrawn, n (%) 10 (12.0) 9 (8.9) 3 (3.0) 8 (8.0) 2 (2.0) Withdrawn due to Adverse Events, n (%) 6 (7.2) 4 (4.0) 0 (0.0) 3 (3.0) 0 (0.0) Withdrawn due to Lack of Efficacy, n (%) Not applicable Withdrawn for other reasons, n (%) 4 (4.8) 5 (5.0) 3 (3.0) 5 (5.0) 2 (2.0) Demographics HIV+/+ HIV+/- HIV- (3+1) HIV- (3+0) HIV- (2+1) N (Total Vaccinated cohort) 83 101 100 100 100 Females:Males 49:34 47:54 58:42 50:50 47:53 Mean Age at Dose 1, weeks (SD) 6.6 (0.92) 6.3 (0.65) 6.1 (0.41) 6.1 (0.35) 6.1 (0.29) African heritage / African American, n (%) 83 (100) 101 (100) 100 (100) 100 (100) 100 (100) Primary Efficacy Results: Seropositivity rates and GMCs for ANTI-1, ANTI-4, ANTI-5, ANTI-6B, ANTI-7F, ANTI-9V, ANTI-14, ANTI-18C, ANTI-19F and ANTI-23F antibodies (22F-inhibition ELISA, ATP cohort for immunogenicity) 0.05 µg/ml 0.2 µg/ml* GMC (µg/ml) 95% CI 95% CI 95% CI Antibody Timing N n % LL UL n % LL UL value LL UL ANTI-1 HIV+/+ PRE 70 34 48.6 36.4 60.8 4 5.7 1.6 14.0 0.05 0.04 0.07 PIII(M3)* 70 70 100 94.9 100 69 98.6 92.3 100 4.00 3.30 4.84 PIII(M8) 66 65 98.5 91.8 100 55 83.3 72.1 91.4 0.54 0.42 0.70 PIV(M9) 66 66 100 94.6 100 66 100 94.6 100 6.64 5.22 8.46 PIV(M23) 63 59 93.7 84.5 98.2 47 74.6 62.1 84.7 0.53 0.35 0.80 HIV+/- PRE 90 36 40.0 29.8 50.9 6 6.7 2.5 13.9 0.04 0.04 0.05 PIII(M3)* 91 90 98.9 94.0 100 90 98.9 94.0 100 3.85 3.26 4.55 PIII(M8) 88 88 100 95.9 100 85 96.6 90.4 99.3 0.84 0.70 1.00 PIV(M9) 89 89 100 95.9 100 89 100 95.9 100 8.64 7.09 10.53 PIV(M23) 86 86 100 95.8 100 74 86.0 76.9 92.6 0.74 0.57 0.95 HIV- (3+1) PRE 93 66 71.0 60.6 79.9 22 23.7 15.5 33.6 0.10 0.07 0.12 PIII(M3)* 93 93 100 96.1 100 93 100 96.1 100 3.36 2.91 3.88 PIII(M8) 93 93 100 96.1 100 82 88.2 79.8 93.9 0.56 0.46 0.68 PIV(M9) 93 93 100 96.1 100 93 100 96.1 100 5.38 4.47 6.48 PIV(M23) 92 92 100 96.1 100 68 73.9 63.7 82.5 0.42 0.34 0.53 HIV- (3+0) PRE 94 58 61.7 51.1 71.5 15 16.0 9.2 25.0 0.07 0.06 0.09 PIII(M3)* 94 94 100 96.2 100 94 100 96.2 100 4.65 3.91 5.53 PIII(M8) 93 93 100 96.1 100 85 91.4 83.8 96.2 0.83 0.68 1.01 PIII(M9) 93 93 100 96.1 100 86 92.5 85.1 96.9 0.72 0.58 0.88 PIII(M23) 90 86 95.6 89.0 98.8 56 62.2 51.4 72.2 0.28 0.22 0.37 HIV- (2+1) PRE 97 65 67.0 56.7 76.2 20 20.6 13.1 30.0 0.08 0.06 0.10 PII(M3) 97 97 100 96.3 100 96 99.0 94.4 100 3.33 2.85 3.88 PII(M8) 97 97 100 96.3 100 87 89.7 81.9 94.9 0.52 0.44 0.60 PIII(M9) 97 97 100 96.3 100 97 100 96.3 100 5.14 4.42 5.97 PIII(M23) 97 95 97.9 92.7 99.7 65 67.0 56.7 76.2 0.33 0.26 0.41 HIV- (3+1) + HIV- (3+0) PRE 187 124 66.3 59.1 73.0 37 19.8 14.3 26.2 0.08 0.07 0.10 PIII(M3)* 187 187 100 98.0 100 187 100 98.0 100 3.96 3.53 4.44
PIII(M8) 186 186 100 98.0 100 167 89.8 84.5 93.7 0.68 0.59 0.78 ANTI-4 HIV+/+ PRE 70 8 11.4 5.1 21.3 2 2.9 0.3 9.9 0.03 0.03 0.04 PIII(M3)* 70 69 98.6 92.3 100 69 98.6 92.3 100 3.67 2.81 4.80 PIII(M8) 65 65 100 94.5 100 59 90.8 81.0 96.5 1.05 0.82 1.35 PIV(M9) 66 66 100 94.6 100 66 100 94.6 100 6.97 5.72 8.50 PIV(M23) 63 61 96.8 89.0 99.6 50 79.4 67.3 88.5 0.56 0.38 0.80 HIV+/- PRE 91 15 16.5 9.5 25.7 0 0.0 0.0 4.0 0.03 0.03 0.03 PIII(M3)* 91 90 98.9 94.0 100 90 98.9 94.0 100 3.14 2.60 3.80 PIII(M8) 88 88 100 95.9 100 86 97.7 92.0 99.7 1.40 1.13 1.73 PIV(M9) 89 89 100 95.9 100 89 100 95.9 100 8.04 6.69 9.68 PIV(M23) 86 85 98.8 93.7 100 74 86.0 76.9 92.6 0.57 0.46 0.71 HIV- (3+1) PRE 93 41 44.1 33.8 54.8 15 16.1 9.3 25.2 0.06 0.05 0.07 PIII(M3)* 93 93 100 96.1 100 93 100 96.1 100 2.71 2.28 3.21 PIII(M8) 93 93 100 96.1 100 88 94.6 87.9 98.2 0.89 0.73 1.08 PIV(M9) 93 93 100 96.1 100 93 100 96.1 100 6.07 5.09 7.24 PIV(M23) 92 90 97.8 92.4 99.7 67 72.8 62.6 81.6 0.44 0.35 0.57 HIV- (3+0) PRE 94 51 54.3 43.7 64.6 14 14.9 8.4 23.7 0.06 0.05 0.08 PIII(M3)* 93 93 100 96.1 100 93 100 96.1 100 3.77 3.09 4.60 PIII(M8) 93 93 100 96.1 100 88 94.6 87.9 98.2 1.13 0.91 1.40 PIII(M9) 93 93 100 96.1 100 87 93.5 86.5 97.6 1.07 0.86 1.34 PIII(M23) 91 87 95.6 89.1 98.8 54 59.3 48.5 69.5 0.33 0.25 0.44 HIV- (2+1) PRE 97 42 43.3 33.3 53.7 10 10.3 5.1 18.1 0.05 0.04 0.06 PII(M3) 97 96 99.0 94.4 100 96 99.0 94.4 100 2.28 1.90 2.75 PII(M8) 97 97 100 96.3 100 92 94.8 88.4 98.3 0.65 0.55 0.77 PIII(M9) 97 97 100 96.3 100 97 100 96.3 100 4.92 4.16 5.81 PIII(M23) 97 93 95.9 89.8 98.9 67 69.1 58.9 78.1 0.34 0.27 0.43 HIV- (3+1) + HIV- (3+0) PRE 187 92 49.2 41.8 56.6 29 15.5 10.6 21.5 0.06 0.05 0.07 PIII(M3)* 186 186 100 98.0 100 186 100 98.0 100 3.19 2.80 3.64 PIII(M8) 186 186 100 98.0 100 176 94.6 90.3 97.4 1.00 0.87 1.16 ANTI-5 HIV+/+ PRE 70 40 57.1 44.7 68.9 7 10.0 4.1 19.5 0.06 0.05 0.08 PIII(M3)* 70 70 100 94.9 100 70 100 94.9 100 4.99 4.00 6.23 PIII(M8) 65 64 98.5 91.7 100 57 87.7 77.2 94.5 0.96 0.72 1.27 PIV(M9) 66 66 100 94.6 100 66 100 94.6 100 7.86 6.25 9.89 PIV(M23) 63 62 98.4 91.5 100 50 79.4 67.3 88.5 0.79 0.55 1.15 HIV+/- PRE 90 36 40.0 29.8 50.9 5 5.6 1.8 12.5 0.04 0.04 0.05 PIII(M3)* 91 90 98.9 94.0 100 90 98.9 94.0 100 4.79 3.96 5.79 PIII(M8) 88 88 100 95.9 100 86 97.7 92.0 99.7 1.36 1.11 1.66 PIV(M9) 89 89 100 95.9 100 89 100 95.9 100 9.48 7.84 11.46 PIV(M23) 86 86 100 95.8 100 78 90.7 82.5 95.9 0.77 0.61 0.97 HIV- (3+1) PRE 93 55 59.1 48.5 69.2 14 15.1 8.5 24.0 0.07 0.06 0.09 PIII(M3)* 93 93 100 96.1 100 93 100 96.1 100 4.41 3.79 5.13 PIII(M8) 93 93 100 96.1 100 92 98.9 94.2 100 1.02 0.86 1.21 PIV(M9) 93 93 100 96.1 100 93 100 96.1 100 8.05 6.70 9.66 PIV(M23) 92 92 100 96.1 100 79 85.9 77.0 92.3 0.72 0.57 0.92 HIV- (3+0) PRE 94 64 68.1 57.7 77.3 14 14.9 8.4 23.7 0.07 0.06 0.09 PIII(M3)* 94 94 100 96.2 100 94 100 96.2 100 5.71 4.84 6.75 PIII(M8) 93 93 100 96.1 100 90 96.8 90.9 99.3 1.57 1.28 1.94 PIII(M9) 93 93 100 96.1 100 90 96.8 90.9 99.3 1.44 1.16 1.77 PIII(M23) 90 88 97.8 92.2 99.7 75 83.3 74.0 90.4 0.45 0.36 0.57 HIV- (2+1) PRE 97 64 66.0 55.7 75.3 11 11.3 5.8 19.4 0.07 0.05 0.08 PII(M3) 97 96 99.0 94.4 100 95 97.9 92.7 99.7 3.45 2.85 4.16 PII(M8) 97 97 100 96.3 100 93 95.9 89.8 98.9 0.99 0.81 1.20 PIII(M9) 97 97 100 96.3 100 97 100 96.3 100 6.96 5.89 8.22 PIII(M23) 97 97 100 96.3 100 82 84.5 75.8 91.1 0.52 0.43 0.64 HIV- (3+1) + HIV- (3+0) PRE 187 119 63.6 56.3 70.5 28 15.0 10.2 20.9 0.07 0.06 0.09 PIII(M3)* 187 187 100 98.0 100 187 100 98.0 100 5.02 4.49 5.62
ANTI- 6B ANTI- 7F PIII(M8) 186 186 100 98.0 100 182 97.8 94.6 99.4 1.27 1.10 1.45 HIV+/+ PRE 70 28 40.0 28.5 52.4 4 5.7 1.6 14.0 0.04 0.04 0.05 PIII(M3)* 70 66 94.3 86.0 98.4 61 87.1 77.0 93.9 1.00 0.73 1.38 PIII(M8) 66 63 95.5 87.3 99.1 56 84.8 73.9 92.5 0.54 0.41 0.71 PIV(M9) 66 65 98.5 91.8 100 63 95.5 87.3 99.1 2.26 1.72 2.98 PIV(M23) 63 59 93.7 84.5 98.2 46 73.0 60.3 83.4 0.67 0.42 1.06 HIV+/- PRE 91 38 41.8 31.5 52.6 5 5.5 1.8 12.4 0.05 0.04 0.06 PIII(M3)* 91 87 95.6 89.1 98.8 80 87.9 79.4 93.8 0.94 0.71 1.24 PIII(M8) 88 85 96.6 90.4 99.3 82 93.2 85.7 97.5 0.79 0.64 0.97 PIV(M9) 89 87 97.8 92.1 99.7 86 96.6 90.5 99.3 2.56 2.01 3.25 PIV(M23) 86 84 97.7 91.9 99.7 74 86.0 76.9 92.6 0.73 0.56 0.97 HIV- (3+1) PRE 93 75 80.6 71.1 88.1 28 30.1 21.0 40.5 0.13 0.10 0.16 PIII(M3)* 93 88 94.6 87.9 98.2 74 79.6 69.9 87.2 0.65 0.50 0.86 PIII(M8) 93 88 94.6 87.9 98.2 82 88.2 79.8 93.9 0.59 0.47 0.74 PIV(M9) 93 90 96.8 90.9 99.3 87 93.5 86.5 97.6 2.05 1.57 2.68 PIV(M23) 92 89 96.7 90.8 99.3 79 85.9 77.0 92.3 0.60 0.47 0.77 HIV- (3+0) PRE 94 61 64.9 54.4 74.5 30 31.9 22.7 42.3 0.11 0.08 0.14 PIII(M3)* 93 91 97.8 92.4 99.7 83 89.2 81.1 94.7 1.06 0.81 1.39 PIII(M8) 93 90 96.8 90.9 99.3 87 93.5 86.5 97.6 0.86 0.70 1.06 PIII(M9) 93 90 96.8 90.9 99.3 89 95.7 89.4 98.8 0.93 0.75 1.15 PIII(M23) 91 90 98.9 94.0 100 75 82.4 73.0 89.6 0.76 0.56 1.03 HIV- (2+1) PRE 97 60 61.9 51.4 71.5 20 20.6 13.1 30.0 0.08 0.06 0.10 PII(M3) 97 94 96.9 91.2 99.4 80 82.5 73.4 89.4 0.57 0.45 0.73 PII(M8) 97 94 96.9 91.2 99.4 80 82.5 73.4 89.4 0.50 0.42 0.60 PIII(M9) 97 95 97.9 92.7 99.7 95 97.9 92.7 99.7 1.98 1.62 2.42 PIII(M23) 97 95 97.9 92.7 99.7 81 83.5 74.6 90.3 0.57 0.44 0.74 HIV- (3+1) + HIV- (3+0) PRE 187 136 72.7 65.7 79.0 58 31.0 24.5 38.2 0.12 0.10 0.14 PIII(M3)* 186 179 96.2 92.4 98.5 157 84.4 78.4 89.3 0.83 0.69 1.01 PIII(M8) 186 178 95.7 91.7 98.1 169 90.9 85.8 94.6 0.71 0.61 0.83 HIV+/+ PRE 70 17 24.3 14.8 36.0 1 1.4 0.0 7.7 0.04 0.03 0.04 PIII(M3)* 70 69 98.6 92.3 100 69 98.6 92.3 100 4.95 3.82 6.41 PIII(M8) 66 65 98.5 91.8 100 61 92.4 83.2 97.5 1.27 0.98 1.64 PIV(M9) 66 66 100 94.6 100 66 100 94.6 100 9.92 7.89 12.47 PIV(M23) 63 62 98.4 91.5 100 59 93.7 84.5 98.2 1.25 0.90 1.75 HIV+/- PRE 90 32 35.6 25.7 46.3 9 10.0 4.7 18.1 0.04 0.04 0.05 PIII(M3)* 91 90 98.9 94.0 100 90 98.9 94.0 100 3.69 3.08 4.41 PIII(M8) 88 88 100 95.9 100 88 100 95.9 100 1.55 1.29 1.85 PIV(M9) 89 89 100 95.9 100 89 100 95.9 100 11.04 9.29 13.11 PIV(M23) 86 86 100 95.8 100 84 97.7 91.9 99.7 1.16 0.96 1.39 HIV- (3+1) PRE 93 74 79.6 69.9 87.2 33 35.5 25.8 46.1 0.15 0.11 0.19 PIII(M3)* 93 93 100 96.1 100 93 100 96.1 100 3.62 3.12 4.19 PIII(M8) 93 93 100 96.1 100 93 100 96.1 100 1.40 1.20 1.63 PIV(M9) 93 93 100 96.1 100 93 100 96.1 100 8.98 7.63 10.56 PIV(M23) 92 92 100 96.1 100 90 97.8 92.4 99.7 1.08 0.92 1.27 HIV- (3+0) PRE 93 67 72.0 61.8 80.9 31 33.3 23.9 43.9 0.11 0.09 0.14 PIII(M3)* 94 94 100 96.2 100 94 100 96.2 100 4.77 4.06 5.60 PIII(M8) 93 93 100 96.1 100 93 100 96.1 100 1.72 1.45 2.03 PIII(M9) 93 93 100 96.1 100 92 98.9 94.2 100 1.78 1.49 2.13 PIII(M23) 91 91 100 96.0 100 80 87.9 79.4 93.8 0.67 0.54 0.83 HIV- (2+1) PRE 97 74 76.3 66.6 84.3 34 35.1 25.6 45.4 0.12 0.09 0.15 PII(M3) 97 96 99.0 94.4 100 96 99.0 94.4 100 2.72 2.30 3.22 PII(M8) 96 96 100 96.2 100 92 95.8 89.7 98.9 1.01 0.85 1.20 PIII(M9) 97 97 100 96.3 100 97 100 96.3 100 6.47 5.59 7.50 PIII(M23) 97 97 100 96.3 100 93 95.9 89.8 98.9 0.84 0.70 1.00 HIV- (3+1) + HIV- (3+0) PRE 186 141 75.8 69.0 81.8 64 34.4 27.6 41.7 0.13 0.10 0.15 PIII(M3)* 187 187 100 98.0 100 187 100 98.0 100 4.16 3.72 4.64
ANTI- 9V ANTI- 14 PIII(M8) 186 186 100 98.0 100 186 100 98.0 100 1.55 1.38 1.74 HIV+/+ PRE 70 27 38.6 27.2 51.0 3 4.3 0.9 12.0 0.05 0.04 0.06 PIII(M3)* 70 68 97.1 90.1 99.7 68 97.1 90.1 99.7 4.53 3.39 6.05 PIII(M8) 66 64 97.0 89.5 99.6 61 92.4 83.2 97.5 1.33 0.96 1.83 PIV(M9) 66 65 98.5 91.8 100 65 98.5 91.8 100 10.09 7.64 13.32 PIV(M23) 63 62 98.4 91.5 100 55 87.3 76.5 94.4 1.15 0.77 1.71 HIV+/- PRE 91 32 35.2 25.4 45.9 9 9.9 4.6 17.9 0.05 0.04 0.06 PIII(M3)* 91 90 98.9 94.0 100 90 98.9 94.0 100 4.25 3.49 5.16 PIII(M8) 88 88 100 95.9 100 88 100 95.9 100 1.72 1.44 2.06 PIV(M9) 89 89 100 95.9 100 89 100 95.9 100 10.89 9.11 13.03 PIV(M23) 86 86 100 95.8 100 85 98.8 93.7 100 1.30 1.04 1.63 HIV- (3+1) PRE 93 74 79.6 69.9 87.2 45 48.4 37.9 59.0 0.19 0.14 0.25 PIII(M3)* 93 93 100 96.1 100 93 100 96.1 100 3.04 2.51 3.69 PIII(M8) 93 93 100 96.1 100 91 97.8 92.4 99.7 1.47 1.20 1.81 PIV(M9) 93 93 100 96.1 100 93 100 96.1 100 9.55 8.06 11.31 PIV(M23) 92 92 100 96.1 100 90 97.8 92.4 99.7 1.05 0.86 1.28 HIV- (3+0) PRE 94 64 68.1 57.7 77.3 27 28.7 19.9 39.0 0.11 0.08 0.14 PIII(M3)* 94 94 100 96.2 100 94 100 96.2 100 5.13 4.35 6.04 PIII(M8) 93 92 98.9 94.2 100 90 96.8 90.9 99.3 1.77 1.44 2.17 PIII(M9) 93 92 98.9 94.2 100 91 97.8 92.4 99.7 1.96 1.58 2.43 PIII(M23) 91 91 100 96.0 100 87 95.6 89.1 98.8 0.85 0.68 1.06 HIV- (2+1) PRE 97 75 77.3 67.7 85.2 32 33.0 23.8 43.3 0.13 0.10 0.18 PII(M3) 97 95 97.9 92.7 99.7 92 94.8 88.4 98.3 2.05 1.61 2.61 PII(M8) 97 94 96.9 91.2 99.4 87 89.7 81.9 94.9 0.87 0.70 1.09 PIII(M9) 97 96 99.0 94.4 100 94 96.9 91.2 99.4 6.51 5.12 8.30 PIII(M23) 97 97 100 96.3 100 88 90.7 83.1 95.7 0.80 0.64 1.00 HIV- (3+1) + HIV- (3+0) PRE 187 138 73.8 66.9 79.9 72 38.5 31.5 45.9 0.14 0.11 0.18 PIII(M3)* 187 187 100 98.0 100 187 100 98.0 100 3.96 3.47 4.51 PIII(M8) 186 185 99.5 97.0 100 181 97.3 93.8 99.1 1.62 1.40 1.86 HIV+/+ PRE 70 65 92.9 84.1 97.6 38 54.3 41.9 66.3 0.24 0.18 0.32 PIII(M3)* 70 69 98.6 92.3 100 69 98.6 92.3 100 7.25 5.37 9.81 PIII(M8) 66 66 100 94.6 100 66 100 94.6 100 4.23 3.31 5.40 PIV(M9) 66 66 100 94.6 100 66 100 94.6 100 11.50 9.17 14.41 PIV(M23) 63 63 100 94.3 100 63 100 94.3 100 2.62 2.02 3.40 HIV+/- PRE 90 88 97.8 92.2 99.7 48 53.3 42.5 63.9 0.29 0.22 0.39 PIII(M3)* 91 90 98.9 94.0 100 90 98.9 94.0 100 6.77 5.43 8.44 PIII(M8) 88 88 100 95.9 100 87 98.9 93.8 100 3.88 3.22 4.66 PIV(M9) 89 89 100 95.9 100 88 98.9 93.9 100 10.58 8.60 13.00 PIV(M23) 86 86 100 95.8 100 85 98.8 93.7 100 2.09 1.69 2.58 HIV- (3+1) PRE 93 93 100 96.1 100 86 92.5 85.1 96.9 1.20 0.92 1.56 PIII(M3)* 93 93 100 96.1 100 93 100 96.1 100 3.85 3.18 4.68 PIII(M8) 93 92 98.9 94.2 100 90 96.8 90.9 99.3 2.62 2.04 3.35 PIV(M9) 93 93 100 96.1 100 92 98.9 94.2 100 7.33 5.94 9.04 PIV(M23) 92 92 100 96.1 100 89 96.7 90.8 99.3 1.32 1.07 1.64 HIV- (3+0) PRE 94 93 98.9 94.2 100 81 86.2 77.5 92.4 1.18 0.89 1.55 PIII(M3)* 93 93 100 96.1 100 93 100 96.1 100 5.27 4.31 6.45 PIII(M8) 93 93 100 96.1 100 90 96.8 90.9 99.3 3.11 2.41 4.01 PIII(M9) 93 93 100 96.1 100 87 93.5 86.5 97.6 2.60 2.01 3.37 PIII(M23) 91 91 100 96.0 100 88 96.7 90.7 99.3 1.24 0.96 1.61 HIV- (2+1) PRE 97 97 100 96.3 100 83 85.6 77.0 91.9 1.03 0.79 1.34 PII(M3) 97 97 100 96.3 100 95 97.9 92.7 99.7 2.51 1.98 3.19 PII(M8) 97 95 97.9 92.7 99.7 89 91.8 84.4 96.4 1.40 1.07 1.83 PIII(M9) 97 97 100 96.3 100 94 96.9 91.2 99.4 5.08 4.03 6.41 PIII(M23) 97 97 100 96.3 100 92 94.8 88.4 98.3 1.06 0.83 1.36 HIV- (3+1) + HIV- (3+0) PRE 187 186 99.5 97.1 100 167 89.3 84.0 93.3 1.19 0.98 1.44 PIII(M3)* 186 186 100 98.0 100 186 100 98.0 100 4.51 3.92 5.19
ANTI- 18C ANTI- 19F PIII(M8) 186 185 99.5 97.0 100 180 96.8 93.1 98.8 2.85 2.39 3.40 HIV+/+ PRE 70 27 38.6 27.2 51.0 6 8.6 3.2 17.7 0.05 0.04 0.06 PIII(M3)* 69 69 100 94.8 100 69 100 94.8 100 9.55 7.19 12.67 PIII(M8) 65 64 98.5 91.7 100 63 96.9 89.3 99.6 2.35 1.67 3.30 PIV(M9) 66 66 100 94.6 100 66 100 94.6 100 20.26 16.13 25.45 PIV(M23) 63 63 100 94.3 100 62 98.4 91.5 100 2.02 1.41 2.89 HIV+/- PRE 90 39 43.3 32.9 54.2 10 11.1 5.5 19.5 0.05 0.04 0.06 PIII(M3)* 91 90 98.9 94.0 100 90 98.9 94.0 100 9.48 7.41 12.13 PIII(M8) 88 88 100 95.9 100 88 100 95.9 100 2.61 2.04 3.33 PIV(M9) 89 89 100 95.9 100 89 100 95.9 100 19.67 15.89 24.35 PIV(M23) 86 86 100 95.8 100 82 95.3 88.5 98.7 1.60 1.22 2.09 HIV- (3+1) PRE 93 68 73.1 62.9 81.8 37 39.8 29.8 50.5 0.13 0.10 0.18 PIII(M3)* 93 93 100 96.1 100 93 100 96.1 100 10.08 8.25 12.31 PIII(M8) 93 93 100 96.1 100 93 100 96.1 100 3.07 2.47 3.82 PIV(M9) 93 93 100 96.1 100 93 100 96.1 100 25.47 21.75 29.83 PIV(M23) 92 92 100 96.1 100 90 97.8 92.4 99.7 1.93 1.58 2.35 HIV- (3+0) PRE 94 70 74.5 64.4 82.9 33 35.1 25.5 45.6 0.13 0.10 0.17 PIII(M3)* 94 94 100 96.2 100 94 100 96.2 100 13.20 10.31 16.90 PIII(M8) 93 93 100 96.1 100 93 100 96.1 100 3.80 2.93 4.94 PIII(M9) 93 93 100 96.1 100 93 100 96.1 100 3.30 2.55 4.27 PIII(M23) 91 91 100 96.0 100 82 90.1 82.1 95.4 0.80 0.63 1.01 HIV- (2+1) PRE 97 66 68.0 57.8 77.1 34 35.1 25.6 45.4 0.11 0.08 0.15 PII(M3) 97 97 100 96.3 100 95 97.9 92.7 99.7 8.65 6.44 11.60 PII(M8) 97 97 100 96.3 100 92 94.8 88.4 98.3 3.40 2.59 4.45 PIII(M9) 97 97 100 96.3 100 97 100 96.3 100 32.29 26.43 39.45 PIII(M23) 97 97 100 96.3 100 97 100 96.3 100 2.44 1.97 3.02 HIV- (3+1) + HIV- (3+0) PRE 187 138 73.8 66.9 79.9 70 37.4 30.5 44.8 0.13 0.11 0.16 PIII(M3)* 187 187 100 98.0 100 187 100 98.0 100 11.54 9.85 13.53 PIII(M8) 186 186 100 98.0 100 186 100 98.0 100 3.42 2.89 4.05 HIV+/+ PRE 70 63 90.0 80.5 95.9 25 35.7 24.6 48.1 0.15 0.11 0.20 PIII(M3)* 70 70 100 94.9 100 68 97.1 90.1 99.7 5.70 4.06 8.02 PIII(M8) 66 65 98.5 91.8 100 60 90.9 81.3 96.6 1.92 1.33 2.79 PIV(M9) 66 66 100 94.6 100 65 98.5 91.8 100 8.00 5.86 10.92 PIV(M23) 63 62 98.4 91.5 100 58 92.1 82.4 97.4 2.01 1.32 3.08 HIV+/- PRE 90 72 80.0 70.2 87.7 34 37.8 27.8 48.6 0.14 0.11 0.18 PIII(M3)* 91 90 98.9 94.0 100 90 98.9 94.0 100 11.15 8.88 13.99 PIII(M8) 88 88 100 95.9 100 88 100 95.9 100 3.14 2.68 3.68 PIV(M9) 89 89 100 95.9 100 89 100 95.9 100 12.46 10.47 14.84 PIV(M23) 86 86 100 95.8 100 85 98.8 93.7 100 2.28 1.72 3.02 HIV- (3+1) PRE 93 92 98.9 94.2 100 77 82.8 73.6 89.8 0.60 0.47 0.77 PIII(M3)* 93 93 100 96.1 100 93 100 96.1 100 8.75 7.37 10.38 PIII(M8) 93 93 100 96.1 100 91 97.8 92.4 99.7 2.32 1.91 2.82 PIV(M9) 93 93 100 96.1 100 92 98.9 94.2 100 8.88 7.37 10.69 PIV(M23) 92 92 100 96.1 100 89 96.7 90.8 99.3 2.53 1.91 3.34 HIV- (3+0) PRE 94 90 95.7 89.5 98.8 71 75.5 65.6 83.8 0.56 0.42 0.74 PIII(M3)* 93 93 100 96.1 100 93 100 96.1 100 10.93 9.20 12.99 PIII(M8) 93 93 100 96.1 100 92 98.9 94.2 100 2.53 2.04 3.15 PIII(M9) 93 93 100 96.1 100 91 97.8 92.4 99.7 2.60 2.03 3.31 PIII(M23) 91 91 100 96.0 100 83 91.2 83.4 96.1 1.59 1.15 2.20 HIV- (2+1) PRE 97 93 95.9 89.8 98.9 65 67.0 56.7 76.2 0.45 0.34 0.60 PII(M3) 96 96 100 96.2 100 94 97.9 92.7 99.7 6.90 5.62 8.48 PII(M8) 97 96 99.0 94.4 100 96 99.0 94.4 100 2.16 1.74 2.69 PIII(M9) 97 96 99.0 94.4 100 96 99.0 94.4 100 9.47 7.42 12.07 PIII(M23) 97 97 100 96.3 100 96 99.0 94.4 100 2.22 1.74 2.84 HIV- (3+1) + HIV- (3+0) PRE 187 182 97.3 93.9 99.1 148 79.1 72.6 84.7 0.58 0.48 0.70 PIII(M3)* 186 186 100 98.0 100 186 100 98.0 100 9.78 8.66 11.04
ANTI- 23F PIII(M8) 186 186 100 98.0 100 183 98.4 95.4 99.7 2.42 2.10 2.80 HIV+/+ PRE 70 33 47.1 35.1 59.4 5 7.1 2.4 15.9 0.05 0.04 0.06 PIII(M3)* 70 68 97.1 90.1 99.7 63 90.0 80.5 95.9 1.71 1.23 2.37 PIII(M8) 66 63 95.5 87.3 99.1 53 80.3 68.7 89.1 0.56 0.41 0.76 PIV(M9) 66 64 97.0 89.5 99.6 60 90.9 81.3 96.6 4.00 2.69 5.93 PIV(M23) 63 63 100 94.3 100 46 73.0 60.3 83.4 0.73 0.49 1.09 HIV+/- PRE 91 37 40.7 30.5 51.5 7 7.7 3.1 15.2 0.05 0.04 0.06 PIII(M3)* 91 86 94.5 87.6 98.2 84 92.3 84.8 96.9 1.52 1.14 2.01 PIII(M8) 88 85 96.6 90.4 99.3 80 90.9 82.9 96.0 0.83 0.65 1.07 PIV(M9) 89 87 97.8 92.1 99.7 85 95.5 88.9 98.8 5.90 4.37 7.96 PIV(M23) 86 85 98.8 93.7 100 75 87.2 78.3 93.4 0.85 0.63 1.14 HIV- (3+1) PRE 93 76 81.7 72.4 89.0 36 38.7 28.8 49.4 0.16 0.12 0.21 PIII(M3)* 93 91 97.8 92.4 99.7 83 89.2 81.1 94.7 0.92 0.72 1.19 PIII(M8) 93 89 95.7 89.4 98.8 77 82.8 73.6 89.8 0.55 0.43 0.70 PIV(M9) 93 90 96.8 90.9 99.3 86 92.5 85.1 96.9 3.83 2.84 5.15 PIV(M23) 92 88 95.7 89.2 98.8 70 76.1 66.1 84.4 0.51 0.39 0.67 HIV- (3+0) PRE 94 66 70.2 59.9 79.2 33 35.1 25.5 45.6 0.12 0.09 0.16 PIII(M3)* 93 93 100 96.1 100 84 90.3 82.4 95.5 1.59 1.21 2.09 PIII(M8) 93 90 96.8 90.9 99.3 81 87.1 78.5 93.2 0.90 0.68 1.21 PIII(M9) 93 90 96.8 90.9 99.3 80 86.0 77.3 92.3 0.92 0.68 1.23 PIII(M23) 90 88 97.8 92.2 99.7 65 72.2 61.8 81.1 0.53 0.38 0.73 HIV- (2+1) PRE 97 58 59.8 49.3 69.6 19 19.6 12.2 28.9 0.08 0.06 0.11 PII(M3) 97 95 97.9 92.7 99.7 84 86.6 78.2 92.7 0.97 0.74 1.27 PII(M8) 97 93 95.9 89.8 98.9 76 78.4 68.8 86.1 0.43 0.34 0.53 PIII(M9) 97 96 99.0 94.4 100 94 96.9 91.2 99.4 3.40 2.67 4.33 PIII(M23) 97 95 97.9 92.7 99.7 69 71.1 61.0 79.9 0.52 0.37 0.72 HIV- (3+1) + HIV- (3+0) PRE 187 142 75.9 69.2 81.9 69 36.9 30.0 44.2 0.14 0.11 0.17 PIII(M3)* 186 184 98.9 96.2 99.9 167 89.8 84.5 93.7 1.21 1.00 1.46 PIII(M8) 186 179 96.2 92.4 98.5 158 84.9 79.0 89.8 0.70 0.58 0.85 GMC = geometric mean antibody concentration N = number of subjects with available results n/% = number/percentage of subjects with concentration within the specified range 95% CI = 95% confidence interval; LL = Lower Limit, UL = Upper Limit PRE = prior to dose 1 PIII(M3)/PII(M3) = 1 month after 10Pn primary vaccination (HIV+/+, HIV+/-, HIV- (3+1), HIV- (3+0) and HIV- (3+1) + HIV- (3+0) s/hiv- (2+1) ) PIII(M8)/PII(M8) = 6 months after 10Pn primary vaccination (HIV+/+, HIV+/-, HIV- (3+1), HIV- (3+0) and HIV- (3+1) + HIV- (3+0) s)/hiv- (2+1) ) PIV(M9) = 1 month after 10Pn booster dose (HIV+/+, HIV+/-, HIV- (3+1) ) PIII(M9) = 1 month after 10Pn booster dose (HIV- (2+1) /7 months after primary vaccination (HIV- (3+0) ) PIII(M23)/PIV(M23)= 21 months after 10Pn primary vaccination (HIV-(3+0) ) / 15 months after 10Pn booster dose (HIV+/+, HIV+/-, HIV-(3+1) & HIV-(2+1) groups) / *Primary outcome variable Secondary Outcome Variable(s): Seropositivity rates and GMTs for OPSONO-1, OPSONO-4, OPSONO-5, OPSONO-6B, OPSONO-7F, OPSONO-9V, OPSONO-14, OPSONO-18C, OPSONO 19F and OPSONO-23F (ATP cohort for immunogenicity) 8 GMT 95% CI 95% CI Antibody Timing N n % LL UL value LL UL OPSONO-1 HIV+/+ PIII(M3) 68 56 82.4 71.2 90.5 139.7 85.2 229.0 PIII(M8) 64 35 54.7 41.7 67.2 19.8 13.2 29.6 PIV(M9) 63 60 95.2 86.7 99.0 1061.5 680.5 1655.8 PIV(M23) 59 32 54.2 40.8 67.3 36.7 19.6 68.9 HIV+/- PIII(M3) 91 79 86.8 78.1 93.0 147.6 102.9 211.7 PIII(M8) 85 45 52.9 41.8 63.9 21.5 14.8 31.2 PIV(M9) 85 83 97.6 91.8 99.7 1377.8 984.9 1927.4
PIV(M23) 84 40 47.6 36.6 58.8 28.1 17.4 45.4 HIV- (3+1) PIII(M3) 93 77 82.8 73.6 89.8 127.2 86.2 187.8 PIII(M8) 92 38 41.3 31.1 52.1 14.1 10.0 19.8 PIV(M9) 90 90 100 96.0 100 1014.8 768.4 1340.3 PIV(M23) 89 41 46.1 35.4 57.0 22.8 14.9 34.9 HIV- (3+0) PIII(M3) 92 86 93.5 86.3 97.6 268.7 196.7 366.9 PIII(M8) 90 54 60.0 49.1 70.2 30.0 20.3 44.4 PIII(M9) 89 48 53.9 43.0 64.6 23.5 16.1 34.4 PIII(M23) 85 26 30.6 21.0 41.5 12.3 8.2 18.6 HIV- (2+1) PII(M3) 96 87 90.6 82.9 95.6 160.6 117.8 218.8 PII(M8) 95 41 43.2 33.0 53.7 14.9 10.8 20.6 PIII(M9) 94 93 98.9 94.2 100 1003.6 763.2 1319.8 PIII(M23) 91 36 39.6 29.5 50.4 13.9 9.8 19.7 HIV- (3+1) + HIV- PIII(M3) 185 163 88.1 82.6 92.4 184.5 143.2 237.7 (3+0) PIII(M8) 182 92 50.5 43.1 58.0 20.5 15.7 26.6 OPSONO-4 HIV+/+ PIII(M3) 67 63 94.0 85.4 98.3 671.6 430.7 1047.5 PIII(M8) 61 46 75.4 62.7 85.5 55.1 33.5 90.7 PIV(M9) 62 62 100 94.2 100 2034.2 1593.5 2596.9 PIV(M23) 53 33 62.3 47.9 75.2 76.6 36.8 159.5 HIV+/- PIII(M3) 91 89 97.8 92.3 99.7 1518.1 1149.7 2004.4 PIII(M8) 85 62 72.9 62.2 82.0 89.8 55.8 144.5 PIV(M9) 86 86 100 95.8 100 3259.0 2579.2 4117.9 PIV(M23) 74 56 75.7 64.3 84.9 141.7 79.2 253.5 HIV- (3+1) PIII(M3) 93 93 100 96.1 100 1711.9 1367.7 2142.9 PIII(M8) 89 57 64.0 53.2 73.9 47.6 30.2 74.8 PIV(M9) 90 89 98.9 94.0 100 2484.7 1919.0 3217.1 PIV(M23) 82 53 64.6 53.3 74.9 125.5 69.1 228.2 HIV- (3+0) PIII(M3) 92 92 100 96.1 100 1890.6 1547.2 2310.2 PIII(M8) 88 62 70.5 59.8 79.7 58.9 36.8 94.3 PIII(M9) 87 72 82.8 73.2 90.0 112.3 70.8 178.1 PIII(M23) 79 28 35.4 25.0 47.0 21.6 12.4 37.5 HIV- (2+1) PII(M3) 96 94 97.9 92.7 99.7 774.8 596.7 1006.0 PII(M8) 92 48 52.2 41.5 62.7 23.0 15.0 35.2 PIII(M9) 95 95 100 96.2 100 1717.6 1406.0 2098.2 PIII(M23) 83 46 55.4 44.1 66.3 58.8 33.0 105.0 HIV- (3+1) + HIV- PIII(M3) 185 185 100 98.0 100 1798.6 1549.1 2088.3 (3+0) PIII(M8) 177 119 67.2 59.8 74.1 52.9 38.3 73.1 OPSONO-5 HIV+/+ PIII(M3) 68 62 91.2 81.8 96.7 105.7 73.8 151.4 PIII(M8) 63 43 68.3 55.3 79.4 22.8 15.8 33.0 PIV(M9) 63 62 98.4 91.5 100 540.4 366.4 796.9 PIV(M23) 57 33 57.9 44.1 70.9 22.5 13.7 37.0 HIV+/- PIII(M3) 91 86 94.5 87.6 98.2 128.6 97.5 169.5 PIII(M8) 86 64 74.4 63.9 83.2 25.1 18.7 33.9 PIV(M9) 85 85 100 95.8 100 531.1 397.3 710.0 PIV(M23) 82 52 63.4 52.0 73.8 19.1 13.9 26.2 HIV- (3+1) PIII(M3) 93 88 94.6 87.9 98.2 107.4 81.8 141.0 PIII(M8) 89 50 56.2 45.3 66.7 18.2 13.2 25.0 PIV(M9) 90 90 100 96.0 100 630.2 447.5 887.7 PIV(M23) 88 54 61.4 50.4 71.6 19.5 14.2 26.7 HIV- (3+0) PIII(M3) 92 89 96.7 90.8 99.3 189.2 147.0 243.5 PIII(M8) 91 65 71.4 61.0 80.4 33.0 23.5 46.4 PIII(M9) 90 68 75.6 65.4 84.0 30.5 21.8 42.5 PIII(M23) 86 30 34.9 24.9 45.9 8.6 6.5 11.3 HIV- (2+1) PII(M3) 96 91 94.8 88.3 98.3 105.7 81.6 136.8 PII(M8) 94 62 66.0 55.5 75.4 21.7 15.8 29.8 PIII(M9) 94 93 98.9 94.2 100 472.7 343.5 650.5
PIII(M23) 89 49 55.1 44.1 65.6 13.3 10.2 17.3 HIV- (3+1) + HIV- PIII(M3) 185 177 95.7 91.7 98.1 142.3 117.9 171.8 (3+0) PIII(M8) 180 115 63.9 56.4 70.9 24.6 19.4 31.1 OPSONO-6B HIV+/+ PIII(M3) 68 49 72.1 59.9 82.3 239.7 123.0 467.4 PIII(M8) 58 43 74.1 61.0 84.7 119.4 61.0 233.8 PIV(M9) 60 55 91.7 81.6 97.2 853.0 467.8 1555.3 PIV(M23) 54 40 74.1 60.3 85.0 100.0 48.8 204.7 HIV+/- PIII(M3) 90 73 81.1 71.5 88.6 480.5 282.1 818.5 PIII(M8) 83 63 75.9 65.3 84.6 142.6 82.0 248.0 PIV(M9) 84 80 95.2 88.3 98.7 986.6 667.6 1457.9 PIV(M23) 81 56 69.1 57.9 78.9 75.5 44.2 128.8 HIV- (3+1) PIII(M3) 92 73 79.3 69.6 87.1 499.5 286.1 872.2 PIII(M8) 88 60 68.2 57.4 77.7 155.3 86.5 278.8 PIV(M9) 88 81 92.0 84.3 96.7 1047.2 679.3 1614.4 PIV(M23) 80 54 67.5 56.1 77.6 116.6 63.7 213.3 HIV- (3+0) PIII(M3) 91 84 92.3 84.8 96.9 1213.7 808.2 1822.6 PIII(M8) 89 74 83.1 73.7 90.2 295.2 179.5 485.4 PIII(M9) 86 73 84.9 75.5 91.7 261.5 161.0 424.7 PIII(M23) 79 57 72.2 60.9 81.7 87.2 48.2 157.7 HIV- (2+1) PII(M3) 92 75 81.5 72.1 88.9 361.2 221.8 588.2 PII(M8) 86 61 70.9 60.1 80.2 84.4 49.6 143.6 PIII(M9) 94 89 94.7 88.0 98.3 945.9 640.0 1398.2 PIII(M23) 83 52 62.7 51.3 73.0 55.9 32.0 97.7 HIV- (3+1) + HIV- PIII(M3) 183 157 85.8 79.9 90.5 776.7 548.3 1100.5 (3+0) PIII(M8) 177 134 75.7 68.7 81.8 214.5 146.2 314.5 OPSONO-7F HIV+/+ PIII(M3) 68 67 98.5 92.1 100 4025.2 2609.7 6208.4 PIII(M8) 63 62 98.4 91.5 100 1522.3 1024.9 2261.0 PIV(M9) 63 63 100 94.3 100 10656.1 7729.9 14690.0 PIV(M23) 55 55 100 93.5 100 6367.5 4511.3 8987.6 HIV+/- PIII(M3) 90 90 100 96.0 100 10158.3 7772.0 13277.2 PIII(M8) 85 85 100 95.8 100 2796.7 2137.5 3659.2 PIV(M9) 85 85 100 95.8 100 18816.6 14352.2 24669.7 PIV(M23) 80 80 100 95.5 100 7396.6 5736.2 9537.6 HIV- (3+1) PIII(M3) 92 92 100 96.1 100 5910.5 4696.9 7437.6 PIII(M8) 89 89 100 95.9 100 2257.7 1738.2 2932.6 PIV(M9) 88 88 100 95.9 100 12108.8 9922.2 14777.4 PIV(M23) 81 81 100 95.5 100 6365.0 5177.2 7825.4 HIV- (3+0) PIII(M3) 92 92 100 96.1 100 6834.5 5280.8 8845.4 PIII(M8) 91 91 100 96.0 100 2037.9 1650.4 2516.5 PIII(M9) 90 90 100 96.0 100 2741.1 2173.7 3456.5 PIII(M23) 77 77 100 95.3 100 5601.1 4334.9 7237.3 HIV- (2+1) PII(M3) 95 94 98.9 94.3 100 2650.0 2002.0 3507.9 PII(M8) 92 91 98.9 94.1 100 1364.1 1002.9 1855.4 PIII(M9) 95 95 100 96.2 100 6029.3 4760.9 7635.6 PIII(M23) 81 81 100 95.5 100 5859.9 4371.4 7855.2 HIV- (3+1) + HIV- PIII(M3) 184 184 100 98.0 100 6355.7 5354.5 7544.2 (3+0) PIII(M8) 180 180 100 98.0 100 2143.8 1815.6 2531.3 OPSONO-9V HIV+/+ PIII(M3) 68 65 95.6 87.6 99.1 1197.2 796.2 1800.1 PIII(M8) 62 53 85.5 74.2 93.1 198.5 118.5 332.4 PIV(M9) 64 63 98.4 91.6 100 2436.8 1736.5 3419.7 PIV(M23) 53 51 96.2 87.0 99.5 507.6 315.2 817.5 HIV+/- PIII(M3) 90 86 95.6 89.0 98.8 1736.5 1224.1 2463.5 PIII(M8) 84 79 94.0 86.7 98.0 395.7 286.1 547.4 PIV(M9) 86 86 100 95.8 100 3215.4 2515.8 4109.6 PIV(M23) 80 75 93.8 86.0 97.9 598.6 396.9 902.7 HIV- (3+1) PIII(M3) 93 91 97.8 92.4 99.7 1672.2 1243.6 2248.4
PIII(M8) 88 83 94.3 87.2 98.1 520.3 366.4 738.9 PIV(M9) 91 91 100 96.0 100 4250.1 3493.4 5170.8 PIV(M23) 85 82 96.5 90.0 99.3 1060.7 761.2 1478.1 HIV- (3+0) PIII(M3) 92 92 100 96.1 100 2216.0 1760.9 2788.8 PIII(M8) 90 86 95.6 89.0 98.8 471.2 337.7 657.3 PIII(M9) 90 88 97.8 92.2 99.7 492.3 351.2 690.1 PIII(M23) 84 76 90.5 82.1 95.8 412.3 267.4 635.9 HIV- (2+1) PII(M3) 96 91 94.8 88.3 98.3 1068.2 759.2 1503.0 PII(M8) 94 75 79.8 70.2 87.4 190.1 120.6 299.5 PIII(M9) 94 91 96.8 91.0 99.3 2572.5 1890.3 3500.8 PIII(M23) 89 81 91.0 83.1 96.0 465.7 318.2 681.6 HIV- (3+1) + HIV- PIII(M3) 185 183 98.9 96.1 99.9 1923.5 1595.4 2319.2 (3+0) PIII(M8) 178 169 94.9 90.6 97.7 494.8 389.5 628.7 OPSONO-14 HIV+/+ PIII(M3) 68 65 95.6 87.6 99.1 2656.2 1686.7 4183.0 PIII(M8) 63 58 92.1 82.4 97.4 420.9 266.4 664.8 PIV(M9) 65 65 100 94.5 100 2205.9 1570.2 3099.0 PIV(M23) 56 50 89.3 78.1 96.0 452.0 270.6 755.0 HIV+/- PIII(M3) 90 90 100 96.0 100 3175.1 2472.8 4077.0 PIII(M8) 86 81 94.2 87.0 98.1 463.6 332.8 645.8 PIV(M9) 87 87 100 95.8 100 2374.3 1923.2 2931.2 PIV(M23) 79 71 89.9 81.0 95.5 472.8 305.1 732.6 HIV- (3+1) PIII(M3) 92 88 95.7 89.2 98.8 1902.7 1300.9 2782.9 PIII(M8) 85 81 95.3 88.4 98.7 440.5 317.8 610.4 PIV(M9) 89 89 100 95.9 100 2180.0 1781.9 2667.0 PIV(M23) 84 72 85.7 76.4 92.4 362.3 229.7 571.6 HIV- (3+0) PIII(M3) 92 92 100 96.1 100 2205.0 1648.8 2948.7 PIII(M8) 89 81 91.0 83.1 96.0 300.4 201.0 448.8 PIII(M9) 87 76 87.4 78.5 93.5 280.0 183.0 428.6 PIII(M23) 76 63 82.9 72.5 90.6 361.5 213.2 613.2 HIV- (2+1) PII(M3) 95 76 80.0 70.5 87.5 380.9 228.1 636.0 PII(M8) 90 66 73.3 63.0 82.1 83.2 52.9 131.1 PIII(M9) 94 94 100 96.2 100 1152.9 910.6 1459.6 PIII(M23) 80 58 72.5 61.4 81.9 185.2 105.8 324.1 HIV- (3+1) + HIV- PIII(M3) 184 180 97.8 94.5 99.4 2048.3 1615.6 2596.8 OPSONO- 18C (3+0) PIII(M8) 174 162 93.1 88.3 96.4 362.1 279.5 469.2 HIV+/+ PIII(M3) 68 63 92.6 83.7 97.6 438.7 284.1 677.3 PIII(M8) 61 38 62.3 49.0 74.4 35.7 21.4 59.4 PIV(M9) 62 62 100 94.2 100 1039.3 770.2 1402.3 PIV(M23) 56 33 58.9 45.0 71.9 21.1 13.0 34.4 HIV+/- PIII(M3) 91 89 97.8 92.3 99.7 575.9 442.9 748.8 PIII(M8) 81 64 79.0 68.5 87.3 54.1 36.2 81.1 PIV(M9) 85 85 100 95.8 100 1036.5 800.1 1342.7 PIV(M23) 71 45 63.4 51.1 74.5 26.7 17.1 41.6 HIV- (3+1) PIII(M3) 91 90 98.9 94.0 100 1046.9 802.6 1365.5 PIII(M8) 88 70 79.5 69.6 87.4 65.2 43.5 97.8 PIV(M9) 90 90 100 96.0 100 1344.4 1074.6 1681.9 PIV(M23) 80 57 71.3 60.0 80.8 48.7 30.4 78.1 HIV- (3+0) PIII(M3) 92 92 100 96.1 100 1203.2 981.2 1475.4 PIII(M8) 88 68 77.3 67.1 85.5 73.9 49.5 110.2 PIII(M9) 90 70 77.8 67.8 85.9 64.5 44.1 94.3 PIII(M23) 83 22 26.5 17.4 37.3 9.8 6.6 14.5 HIV- (2+1) PII(M3) 93 91 97.8 92.4 99.7 1052.3 777.7 1423.8 PII(M8) 93 73 78.5 68.8 86.3 57.2 39.2 83.5 PIII(M9) 93 92 98.9 94.2 100 1441.3 1111.7 1868.5 PIII(M23) 78 61 78.2 67.4 86.8 41.6 27.3 63.3 HIV- (3+1) + HIV- PIII(M3) 183 182 99.5 97.0 100 1122.8 951.1 1325.4
(3+0) PIII(M8) 176 138 78.4 71.6 84.2 69.4 52.4 92.0 OPSONO- HIV+/+ PIII(M3) 68 56 82.4 71.2 90.5 228.6 132.5 394.4 19F PIII(M8) 61 49 80.3 68.2 89.4 54.7 34.5 86.8 PIV(M9) 61 53 86.9 75.8 94.2 488.2 275.3 865.9 PIV(M23) 55 39 70.9 57.1 82.4 41.8 23.5 74.4 HIV+/- PIII(M3) 91 86 94.5 87.6 98.2 590.3 418.9 831.6 PIII(M8) 86 78 90.7 82.5 95.9 67.3 49.8 90.8 PIV(M9) 86 84 97.7 91.9 99.7 1357.5 976.2 1887.8 PIV(M23) 74 64 86.5 76.5 93.3 73.2 47.1 114.0 HIV- (3+1) PIII(M3) 92 91 98.9 94.1 100 511.9 394.1 664.9 PIII(M8) 91 69 75.8 65.7 84.2 40.3 28.3 57.2 PIV(M9) 89 85 95.5 88.9 98.8 730.8 516.5 1034.1 PIV(M23) 86 64 74.4 63.9 83.2 52.5 33.2 83.1 HIV- (3+0) PIII(M3) 92 91 98.9 94.1 100 649.3 481.1 876.2 PIII(M8) 89 71 79.8 69.9 87.6 53.7 37.2 77.6 PIII(M9) 88 68 77.3 67.1 85.5 46.8 31.6 69.5 PIII(M23) 82 50 61.0 49.6 71.6 28.2 17.8 44.6 HIV- (2+1) PII(M3) 95 88 92.6 85.4 97.0 275.9 193.4 393.5 PII(M8) 93 68 73.1 62.9 81.8 36.1 25.2 51.8 PIII(M9) 94 87 92.6 85.3 97.0 630.3 422.9 939.5 PIII(M23) 85 59 69.4 58.5 79.0 47.6 30.1 75.1 HIV- (3+1) + HIV- PIII(M3) 184 182 98.9 96.1 99.9 576.5 473.0 702.6 (3+0) PIII(M8) 180 140 77.8 71.0 83.6 46.4 36.1 59.8 OPSONO- HIV+/+ PIII(M3) 68 52 76.5 64.6 85.9 338.0 174.1 656.2 23F PIII(M8) 61 34 55.7 42.4 68.5 39.5 20.8 75.0 PIV(M9) 63 56 88.9 78.4 95.4 1327.4 736.2 2393.5 PIV(M23) 53 28 52.8 38.6 66.7 97.6 38.2 249.6 HIV+/- PIII(M3) 89 75 84.3 75.0 91.1 769.6 451.1 1312.9 PIII(M8) 76 47 61.8 50.0 72.8 72.0 38.6 134.3 PIV(M9) 87 82 94.3 87.1 98.1 2120.7 1359.4 3308.1 PIV(M23) 78 47 60.3 48.5 71.2 154.8 71.7 334.2 HIV- (3+1) PIII(M3) 88 76 86.4 77.4 92.8 864.1 511.2 1460.6 PIII(M8) 84 46 54.8 43.5 65.7 59.9 32.4 110.8 PIV(M9) 90 81 90.0 81.9 95.3 2144.8 1312.5 3504.8 PIV(M23) 80 34 42.5 31.5 54.1 69.7 31.7 153.1 HIV- (3+0) PIII(M3) 92 81 88.0 79.6 93.9 1107.0 683.0 1794.0 PIII(M8) 85 53 62.4 51.2 72.6 100.5 54.9 184.0 PIII(M9) 86 55 64.0 52.9 74.0 83.6 47.2 148.0 PIII(M23) 78 36 46.2 34.8 57.8 92.7 40.7 211.2 HIV- (2+1) PII(M3) 91 76 83.5 74.3 90.5 509.6 306.8 846.6 PII(M8) 89 38 42.7 32.3 53.6 35.2 19.5 63.7 PIII(M9) 95 87 91.6 84.1 96.3 1557.2 1012.2 2395.7 PIII(M23) 80 39 48.8 37.4 60.2 103.5 47.0 227.7 HIV- (3+1) + HIV- PIII(M3) 180 157 87.2 81.4 91.7 980.7 689.0 1396.0 (3+0) PIII(M8) 169 99 58.6 50.8 66.1 77.7 50.6 119.3 GMT = geometric mean titre N = number of subjects with available results n/% = number/percentage of subjects with titre within the specified range 95% CI = 95% confidence interval; LL = Lower Limit, UL = Upper Limit PIII(M3)/PII(M3) = 1 month after 10Pn primary vaccination (HIV+/+, HIV+/-, HIV- (3+1), HIV- (3+0) and HIV- (3+1) + HIV- (3+0) s/hiv- (2+1) ) PIII(M8)/PII(M8) = 6 months after 10Pn primary vaccination (HIV+/+, HIV+/-, HIV- (3+1), HIV- (3+0) and HIV- (3+1) + HIV- (3+0) s/hiv- (2+1) ) PIV(M9) = 1 month after 10Pn booster dose (HIV+/+, HIV+/-, HIV- (3+1) ) PIII(M9) = 1 month after 10Pn booster dose (HIV- (2+1) /7 months after primary vaccination (HIV- (3+0) )) PIII(M23)/PIV(M23)= 21 months after 10Pn primary vaccination (HIV-(3+0) )/ 15 months after 10Pn booster dose
(HIV+/+, HIV+/-, HIV-(3+1) & HIV-(2+1) groups) Secondary Outcome Variable(s): Seropositivity rates and GMCs for ANTI-6A and ANTI-19A antibodies (22F-inhibition ELISA, ATP cohort for immunogenicity) 0.05 µg/ml 0.2 µg/ml GMC (µg/ml) 95% CI 95% CI 95% CI Antibody Timing N n % LL UL n % LL UL value LL UL ANTI-6A HIV+/+ HIV+/- HIV- (3+1) HIV- (3+0) HIV- (2+1) HIV- (3+1) + HIV- (3+0) ANTI-19A HIV+/+ HIV+/- HIV- (3+1) PRE 70 40 57.1 44.7 68.9 6 8.6 3.2 17.7 0.06 0.05 0.07 PIII(M3) 70 64 91.4 82.3 96.8 23 32.9 22.1 45.1 0.15 0.12 0.19 PIII(M8) 66 58 87.9 77.5 94.6 23 34.8 23.5 47.6 0.15 0.11 0.20 PIV(M9) 66 63 95.5 87.3 99.1 50 75.8 63.6 85.5 0.48 0.34 0.67 PIV(M23) 63 50 79.4 67.3 88.5 26 41.3 29.0 54.4 0.23 0.14 0.38 PRE 90 42 46.7 36.1 57.5 13 14.4 7.9 23.4 0.06 0.04 0.07 PIII(M3) 91 78 85.7 76.8 92.2 25 27.5 18.6 37.8 0.12 0.10 0.15 PIII(M8) 88 77 87.5 78.7 93.6 36 40.9 30.5 51.9 0.17 0.13 0.22 PIV(M9) 89 89 100 95.9 100 66 74.2 63.8 82.9 0.58 0.43 0.77 PIV(M23) 86 75 87.2 78.3 93.4 43 50.0 39.0 61.0 0.25 0.17 0.35 PRE 93 81 87.1 78.5 93.2 33 35.5 25.8 46.1 0.17 0.13 0.23 PIII(M3) 93 80 86.0 77.3 92.3 26 28.0 19.1 38.2 0.12 0.10 0.15 PIII(M8) 93 70 75.3 65.2 83.6 27 29.0 20.1 39.4 0.11 0.09 0.14 PIV(M9) 93 86 92.5 85.1 96.9 59 63.4 52.8 73.2 0.36 0.27 0.49 PIV(M23) 92 75 81.5 72.1 88.9 47 51.1 40.4 61.7 0.20 0.15 0.27 PRE 94 71 75.5 65.6 83.8 29 30.9 21.7 41.2 0.13 0.10 0.16 PIII(M3) 93 83 89.2 81.1 94.7 29 31.2 22.0 41.6 0.13 0.11 0.16 PIII(M8) 93 73 78.5 68.8 86.3 45 48.4 37.9 59.0 0.20 0.15 0.27 PIII(M9) 93 82 88.2 79.8 93.9 48 51.6 41.0 62.1 0.21 0.15 0.28 PIII(M23) 91 76 83.5 74.3 90.5 46 50.5 39.9 61.2 0.25 0.18 0.36 PRE 97 76 78.4 68.8 86.1 22 22.7 14.8 32.3 0.10 0.08 0.13 PII(M3) 97 77 79.4 70.0 86.9 24 24.7 16.5 34.5 0.11 0.09 0.13 PII(M8) 97 68 70.1 60.0 79.0 29 29.9 21.0 40.0 0.10 0.08 0.13 PIII(M9) 97 92 94.8 88.4 98.3 66 68.0 57.8 77.1 0.36 0.28 0.47 PIII(M23) 97 81 83.5 74.6 90.3 44 45.4 35.2 55.8 0.19 0.14 0.26 PRE 187 152 81.3 74.9 86.6 62 33.2 26.5 40.4 0.15 0.12 0.18 PIII(M3) 186 163 87.6 82.0 92.0 55 29.6 23.1 36.7 0.13 0.11 0.15 PIII(M8) 186 143 76.9 70.2 82.7 72 38.7 31.7 46.1 0.15 0.12 0.18 PRE 70 59 84.3 73.6 91.9 16 22.9 13.7 34.4 0.10 0.08 0.13 PIII(M3) 69 59 85.5 75.0 92.8 26 37.7 26.3 50.2 0.16 0.12 0.23 PIII(M8) 65 54 83.1 71.7 91.2 40 61.5 48.6 73.3 0.27 0.18 0.41 PIV(M9) 66 59 89.4 79.4 95.6 52 78.8 67.0 87.9 0.99 0.61 1.61 PIV(M23) 63 54 85.7 74.6 93.3 35 55.6 42.5 68.1 0.45 0.26 0.76 PRE 90 59 65.6 54.8 75.3 27 30.0 20.8 40.6 0.10 0.07 0.12 PIII(M3) 91 84 92.3 84.8 96.9 52 57.1 46.3 67.5 0.28 0.21 0.36 PIII(M8) 88 80 90.9 82.9 96.0 59 67.0 56.2 76.7 0.32 0.24 0.43 PIV(M9) 89 87 97.8 92.1 99.7 77 86.5 77.6 92.8 1.48 1.06 2.08 PIV(M23) 86 74 86.0 76.9 92.6 56 65.1 54.1 75.1 0.47 0.31 0.72 PRE 93 85 91.4 83.8 96.2 57 61.3 50.6 71.2 0.29 0.21 0.39 PIII(M3) 93 85 91.4 83.8 96.2 51 54.8 44.2 65.2 0.20 0.16 0.25 PIII(M8) 93 80 86.0 77.3 92.3 43 46.2 35.8 56.9 0.17 0.13 0.21 PIV(M9) 93 91 97.8 92.4 99.7 70 75.3 65.2 83.6 0.78 0.57 1.07 PIV(M23) 92 81 88.0 79.6 93.9 61 66.3 55.7 75.8 0.53 0.35 0.80 HIV- (3+0) PRE 94 81 86.2 77.5 92.4 55 58.5 47.9 68.6 0.28 0.21 0.38 PIII(M3) 92 87 94.6 87.8 98.2 57 62.0 51.2 71.9 0.29 0.23 0.38 PIII(M8) 93 78 83.9 74.8 90.7 49 52.7 42.1 63.1 0.24 0.17 0.33 PIII(M9) 93 77 82.8 73.6 89.8 52 55.9 45.2 66.2 0.26 0.19 0.37 PIII(M23) 89 79 88.8 80.3 94.5 57 64.0 53.2 73.9 0.41 0.28 0.60 HIV- (2+1) PRE 97 88 90.7 83.1 95.7 57 58.8 48.3 68.7 0.27 0.20 0.35
PII(M3) 97 91 93.8 87.0 97.7 57 58.8 48.3 68.7 0.25 0.20 0.32 PII(M8) 97 79 81.4 72.3 88.6 49 50.5 40.2 60.8 0.19 0.14 0.27 PIII(M9) 97 91 93.8 87.0 97.7 80 82.5 73.4 89.4 1.04 0.72 1.49 PIII(M23) 97 90 92.8 85.7 97.0 63 64.9 54.6 74.4 0.58 0.41 0.83 HIV- (3+1) + HIV- (3+0) PRE 187 166 88.8 83.3 92.9 112 59.9 52.5 67.0 0.29 0.23 0.35 PIII(M3) 185 172 93.0 88.3 96.2 108 58.4 50.9 65.6 0.24 0.20 0.29 PIII(M8) 186 158 84.9 79.0 89.8 92 49.5 42.1 56.9 0.20 0.16 0.25 GMC = geometric mean antibody concentration N = number of subjects with available results n/% = number/percentage of subjects with concentration within the specified range 95% CI = 95% confidence interval; LL = Lower Limit, UL = Upper Limit PRE = prior to dose 1 PIII(M3)/PII(M3) = 1 month after 10Pn primary vaccination (HIV+/+, HIV+/-, HIV- (3+1), HIV- (3+0) and HIV- (3+1) + HIV- (3+0) s/hiv- (2+1) PIII(M8)/PII(M8) = 6 months after 10Pn primary vaccination (HIV+/+, HIV+/-, HIV- (3+1), HIV- (3+0) and HIV- (3+1) + HIV- (3+0) s/hiv- (2+1) PIV(M9) = 1 month after 10Pn booster dose (HIV+/+, HIV+/-, HIV- (3+1) s) PIII(M9) = 1 month after 10Pn booster dose (HIV- (2+1) /7 months after primary vaccination (HIV- (3+0) ) PIII(M23)/PIV(M23)= 21 months after 10Pn primary vaccination (HIV-(3+0) ) / 15 months after 10Pn booster dose (HIV+/+, HIV+/-, HIV-(3+1) & HIV-(2+1) groups) Secondary Outcome Variable(s): Seropositivity rates and GMTs for OPSONO-6A and OPSONO-19A (ATP cohort for immunogenicity) 8 GMT 95% CI 95% CI Antibody Timing N n % LL UL value LL UL OPSONO-6A HIV+/+ PIII(M3) 67 10 14.9 7.4 25.7 7.7 5.2 11.5 PIII(M8) 63 17 27.0 16.6 39.7 10.8 6.7 17.3 PIV(M9) 64 27 42.2 29.9 55.2 26.4 14.7 47.3 PIV(M23) 53 13 24.5 13.8 38.3 14.2 7.5 27.2 HIV+/- PIII(M3) 91 19 20.9 13.1 30.7 11.5 7.4 17.9 PIII(M8) 83 24 28.9 19.5 39.9 15.5 9.5 25.5 PIV(M9) 86 41 47.7 36.8 58.7 38.6 22.2 67.0 PIV(M23) 79 23 29.1 19.4 40.4 15.7 9.4 26.2 HIV- (3+1) PIII(M3) 89 21 23.6 15.2 33.8 12.1 7.8 18.9 PIII(M8) 85 19 22.4 14.0 32.7 11.2 7.3 17.3 PIV(M9) 83 39 47.0 35.9 58.3 40.4 22.9 71.4 PIV(M23) 79 28 35.4 25.0 47.0 20.5 12.2 34.3 HIV- (3+0) PIII(M3) 91 26 28.6 19.6 39.0 13.8 9.1 20.9 PIII(M8) 88 28 31.8 22.3 42.6 16.5 10.3 26.3 PIII(M9) 86 18 20.9 12.9 31.0 9.5 6.5 14.0 PIII(M23) 79 18 22.8 14.1 33.6 15.3 8.5 27.5 HIV- (2+1) PII(M3) 95 17 17.9 10.8 27.1 8.1 5.8 11.3 PII(M8) 88 19 21.6 13.5 31.6 10.0 6.8 14.7 PIII(M9) 94 48 51.1 40.5 61.5 42.2 25.5 69.9 PIII(M23) 79 27 34.2 23.9 45.7 19.0 11.4 31.9 OPSONO- 19A HIV- (3+1) + HIV- PIII(M3) 180 47 26.1 19.9 33.2 12.9 9.5 17.5 (3+0) PIII(M8) 173 47 27.2 20.7 34.4 13.6 9.9 18.7 HIV+/+ PIII(M3) 66 17 25.8 15.8 38.0 9.5 6.4 14.0 PIII(M8) 62 19 30.6 19.6 43.7 9.2 6.4 13.4 PIV(M9) 63 41 65.1 52.0 76.7 42.0 24.8 71.2 PIV(M23) 56 25 44.6 31.3 58.5 19.9 11.4 34.8 HIV+/- PIII(M3) 91 38 41.8 31.5 52.6 15.2 10.4 22.2 PIII(M8) 86 24 27.9 18.8 38.6 9.1 6.6 12.6 PIV(M9) 86 66 76.7 66.4 85.2 101.8 63.9 162.3 PIV(M23) 79 31 39.2 28.4 50.9 15.8 10.0 24.8 HIV- (3+1) PIII(M3) 93 30 32.3 22.9 42.7 10.6 7.7 14.7