Table A1.

Primary and secondary endpoint description

Co-primary immunogenicity endpoint	To demonstrate non-inferiority of AS04-HPV-16/18 versus (vs.) 4vHPV in terms of geometric mean titers (GMTs) against HPV-16 and HPV-18 measured by Pseudovirion-based neutralization assay (PBNA) one month after administration of the third dose of vaccine in HIV+ subjects. Criterion: Non-inferiority was to be demonstrated if the lower limit of the 95% confidence interval (CI) for the ratio of GMTs (AS04-HPV-16/18 over 4vHPV) was above 0·5 for both HPV types.
	If non-inferiority was demonstrated, demonstrate superiority of AS04-HPV-16/18 over 4vHPV in terms of GMTs against HPV-16 and HPV-18 measured by PBNA in HIV+ subjects assessed in a sequential approach: -First, superiority for HPV-18 type -Second, if superiority for HPV-18 was shown, superiority for HPV-16 was to be assessed. Criterion: Superiority was to be demonstrated if the lower limit of the 95% CI for the ratio of GMTs (AS04-HPV-16/18 over 4vHPV) was above 1 for HPV-18 type with a statistically significant p-value. Superiority was to be demonstrated if the lower limit of the 95% CI for the ratio of GMTs (AS04-HPV-16/18 over 4vHPV) was above 1 for HPV-16 type with a statistically significant p-value.
Co-primary safety endpoint	Safety: safety and reactogenicity of both vaccines in HIV+ subjects for up to one month after the third dose of vaccine (up to month 7). •Occurrence and intensity of solicited local symptoms within seven days of vaccination in HIV+ subjects. •Occurrence, intensity and relationship to vaccination of solicited general symptoms within seven days of vaccination in HIV+ subjects. •Occurrence, intensity and relationship to vaccination of unsolicited symptoms within 30 days of vaccination in HIV+ subjects. •Occurrence of serious adverse events (SAEs) up to 30 days after the last dose of vaccine (i.e., Month 7) in HIV+ subjects. •Occurrence of medically-significant conditions (including potentially immune-mediated diseases [pIMDs]) up to 30 days after the last dose of vaccine (i.e., Month 7) in HIV+ subjects. •Occurrence and outcome of pregnancies up to 30 days after the last dose of vaccine (i.e., Month 7) in HIV+ subjects. •Occurrence of clinically-relevant abnormalities in haematological and biochemical parameters up to 30 days after the last dose of vaccine (i.e., Month 7) in HIV+ subjects. •CD4 cell count up to 30 days after the last dose of vaccine (i.e., Month 7) in HIV+ subjects. •HIV viral load up to 30 days after the last dose of vaccine (i.e., Month 7) in HIV+ subjects. •HIV clinical staging up to 30 days after the last dose of vaccine (i.e., Month 7) in HIV+ subjects.
Secondary immunogenicity endpoints	To demonstrate superiority of AS04-HPV-16/18 vs. 4vHPV in terms of GMTs against HPV-16 or HPV-18 measured by PBNA one month after the administration of the third dose of vaccine in HIV- subjects. Criterion: Superiority of AS04-HPV-16/18 vs. 4vHPV was to be demonstrated if the lower limit of the 97·5% CI for the ratio of GMTs (AS04-HPV-16/18 over 4vHPV) was above 1 for the antigen considered with a statistically significant p-value.
	To evaluate the antibody response of both vaccines with respect to HPV-16 and HPV-18 antibody titers and total IgG titers by Enzyme-Linked Immunosorbent Assay (ELISA) in serum at Day 0, Week 6, Week 10, Months 7, 12, 18 and 24 in all (HIV+ and HIV-) subjects.
	To evaluate the antibody response with respect to HPV-16 and HPV-18 antibody titers and total IgG titers, by ELISA in cervico-vaginal secretions (CVS) at Day 0, Week 6, Week 10, Months 7, 12 and 24 in post-menarcheal subjects who volunteer for this procedure.
	To evaluate the memory B and T cell-mediated immune (CMI) response (frequencies of HPV-16 and HPV-18 specific B-cells and T cells) at Day 0, Week 6, Week 10, Months 7 and 12 in a subset of approximately 100 subjects (50 HIV+ and 50 HIV-).
Secondary safety endpoints	Safety: Safety and reactogenicity of both vaccines in HIV- subjects for up to one month after the third dose of vaccine. Safety and reactogenicity of both vaccines in all subjects for up to 24 months after the first vaccine dose