Immunogenicity and safety of the AS04-HPV-16/18 and HPV-6/11/16/18 human papillomavirus vaccines in asymptomatic young women living with HIV aged 15-25 years: A phase IV randomized comparative study

Nicolas Folschweiller; Julio Teixeira; Smita Joshi; Luciano Z Goldani; Khuanchai Supparatpinyo; Partha Basu; Tawee Chotpitayasunondh; Ploenchan Chetchotisakd; Kiat Ruxrungtham; Cecilia Roteli-Martins; Beatriz Grinsztejn; Silvana Maria Quintana; Nagalingeswaran Kumarasamy; Selvamuthu Poongulali; Vinay Kulkarni; Lan Lin; Sanjoy K Datta; Dominique Descamps; Monique Dodet; Gary Dubin; Damien Friel; Marjan Hezareh; Naveen Karkada; Dorothee Meric Camilleri; Sylviane Poncelet; Bruno Salaun; Fernanda Tavares-da-Silva; Florence Thomas-Jooris; Frank Struyf

doi:10.1016/j.eclinm.2020.100353

Immunogenicity and safety of the AS04-HPV-16/18 and HPV-6/11/16/18 human papillomavirus vaccines in asymptomatic young women living with HIV aged 15-25 years: A phase IV randomized comparative study

EClinicalMedicine. 2020 May 25:23:100353. doi: 10.1016/j.eclinm.2020.100353. eCollection 2020 Jun.

Authors

Nicolas Folschweiller¹, Julio Teixeira², Smita Joshi³, Luciano Z Goldani⁴, Khuanchai Supparatpinyo⁵, Partha Basu⁶, Tawee Chotpitayasunondh⁷, Ploenchan Chetchotisakd⁸, Kiat Ruxrungtham⁹, Cecilia Roteli-Martins¹⁰, Beatriz Grinsztejn¹¹, Silvana Maria Quintana¹², Nagalingeswaran Kumarasamy¹³, Selvamuthu Poongulali¹³, Vinay Kulkarni³, Lan Lin¹, Sanjoy K Datta¹⁴, Dominique Descamps¹, Monique Dodet¹⁵, Gary Dubin¹, Damien Friel¹, Marjan Hezareh¹⁶, Naveen Karkada¹, Dorothee Meric Camilleri¹, Sylviane Poncelet¹⁵, Bruno Salaun¹⁵, Fernanda Tavares-da-Silva¹, Florence Thomas-Jooris¹, Frank Struyf¹

Affiliations

¹ GSK, Avenue Fleming 20, 1300 Wavre, Belgium.
² University of Campinas, Campinas, Brazil.
³ Jehangir Clinical Development Centre and Prayas, Pune, India.
⁴ Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre Brazil.
⁵ Chiang Mai University, Chiang Mai, Thailand.
⁶ Chittaranjan National Cancer Institute, Kolkata, India.
⁷ Queen Sirikit National Institute of Child Health, Bangkok, Thailand.
⁸ Khon Kaen University, Khon Kaen, Thailand.
⁹ Chulalongkorn University and HIVNAT, TRC-ARC, Bangkok, Thailand.
¹⁰ ABC Medical School, Santo André, São Paulo, Brazil.
¹¹ Instituto de pesquisa Clínica Evandro Chagas (IPEC), Rio de Janeiro, Brazil.
¹² Ribeirão Preto Medical School, University of São Paulo (USP), São Paulo, Brazil.
¹³ Infectious Diseases Medical Centre, Voluntary Health Services, Chennai, India.
¹⁴ GSK, Singapore, Singapore.
¹⁵ GSK, Rixensart, Belgium.
¹⁶ Chiltern international for GSK, Wavre, Belgium.

Abstract

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/mm³.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.

Keywords: 4-valent HPV vaccine; AS04-HPV-16/18 vaccine; HIV; HPV; Immunogenicity; Safety; Vaccine.

Associated data

ClinicalTrials.gov/NCT01031069