Folschweiller N, Teixeira J, Joshi S, Goldani LZ, Supparatpinyo K, Basu P, Chotpitayasunondh T, Chetchotisakd P, Ruxrungtham K, Roteli-Martins C, Grinsztejn B, Quintana SM, Kumarasamy N, Poongulali S, Kulkarni V, Lin L, Datta SK, Descamps D, Dodet M, Dubin G, Friel D, Hezareh M, Karkada N, Meric Camilleri D, Poncelet S, Salaun B, Tavares-da-Silva F, Thomas-Jooris F, and Struyf F
Background: Women living with HIV (WLWH) are at higher risk of acquisition and progression of human papillomavirus (HPV) infection. Evidence on effect of HPV vaccination in this population is limited., Methods: This phase IV randomized controlled observer-blind study assessed immunogenicity and safety of two HPV vaccines (AS04-HPV-16/18 vs. 4vHPV) given in WLWH (stage 1) and HIV- females aged 15-25 years. Co-primary endpoints were to demonstrate, in WLWH subjects, non-inferiority (and if demonstrated, superiority) of AS04-HPV-16/18 vs. 4vHPV for HPV-16 and HPV-18 by pseudovirion-based neutralization assay (PBNA) at month 7 and safety. Non-inferiority criteria was lower limit (LL) of the 95% confidence interval (CI) of the GMT ratio AS04-HPV-16/18/4vHPV above 0.5, in the according to protocol population. NCT01031069., Findings: Among 873 subjects recruited between 26-Oct-2010 and 14-May-2015, 546 were randomized (1:1) and received at least one vaccine dose (total vaccinated cohort, TVC): 257 were WLWH (129 AS04-HPV-16/18; 128 4vHPV) and 289 were subjects without HIV (144 AS04-HPV-16/18; 145 4vHPV). Baseline CD4 cell count in WLWH was at least 350 cells/mm 3 .At month 7, AS04-HPV-16/18 showed immunological superiority to 4vHPV in WLWH. Neutralizing anti-HPV-16 and HPV-18 antibody GMTs were 2·74 (95% CI: 1·83; 4·11) and 7·44 (95% CI: 4·79; 11·54) fold higher in AS04-HPV-16/18 vs. 4vHPV (LL of the GMT ratio >1 in TVC, p <0·0001), respectively. Similar results were observed by ELISA up to month 24.Solicited local and general symptoms were in line with product labels. The number of reported serious adverse events (SAEs) was balanced throughout the study., Interpretation: Both vaccines showed an acceptable safety profile in all subjects. Despite the absence of an immunological correlate of protection for HPV, differences in immune responses elicited by the vaccines especially for HPV-18 may translate into longer lasting or more robust protection against cervical cancer with the AS04-HPV-16/18 vaccine in WLWH., Competing Interests: N Folschweiller is an employee of the GSK group of companies and holds shares in the GSK group of companies. J Teixeira, S Joshi, K Supparatpinyo, and K Ruxrungtham report grants from the GSK group of companies for the conduct of the study. K Ruxrungtham also received honoraria or consultation fees from Merck, Roche, Jensen-Cilag, Tibotec, Myland and GPO (Governmental pharmaceutical organization, Thailand) and participated in a company sponsored speaker's bureau from Abbott, Gilead, Bristol-Myers Squibb, Merck, Roche, Jensen-Cilag, GSK, and Thai GPO. L Goldani, P Basu, C Roteli-Martins, B Grinsztejn, S Quintana, N Kumarasamy, S Poongulali and V Kulkarni report no conflict of interest. T Chotpitayasunondh reports grant for the study conduct and speaker honorarium outside of the present work, from the GSK group of companies. P Chetchotisakd reports grant from the GSK group of companies for the study conduct and from Gilead outside of the present work. L Lin, S Datta, D Descamps, F Tavares da Silva, D Friel, S Poncelet, and B Salaun are employees of the GSK group of companies and hold shares in the GSK group of companies. M Dodet, N Karkada are employees of the GSK group of companies. G Dubin was an employee of the GSK group of companies during the study conduct, holds shares in the GSK group of companies, and is currently an employee of Takeda Pharmaceuticals. F Struyf was an employee of the GSK group of companies during the study conduct, holds shares in the GSK group of companies, and is currently an employee of Janssen, Pharmaceutical Companies of Johnson & Johnson. M Hezareh reports consulting fees for her institution from the GSK group of companies. D Meric Camilleri was an employee of the GSK group of companies and held shares in the company at the time of the study. F Thomas-Jooris was an employee of the GSK group of companies at the time of the study and hold shares in the GSK group of companies., (© 2020 The Author(s).)