Immunogenicity and safety of two versus three doses of 9-valent vaccine against Human papillomavirus (HPV) in women with HIV: the Papillon randomized trial

Abstract

Background: WHO recommends 2 doses of HPV vaccine for adults without HIV but 3 doses in persons with HIV. There are no immunogenicity data on the 2 doses schedule in women with HIV (WWH).

Methods: Prospective study comparing 2 (month (M) 0,6) versus 3 (M 0,2,6) doses of 9-valent (9v) vaccine (Gardasil9®MSD) in WWH (15-40 years), on antiretrovirals with HIVRNA<400cp/ml; enrollment 2018-2021. After an open-label phase assessing safety (n=45 receiving 3 doses), participants were randomized between 2 or 3 doses. Primary outcome was non-inferiority of 2 doses compared to 3 doses for seroconversion against all vaccine genotypes. Due to COVID-19 pandemic, 100 WWH, instead of initially planned 120, were randomized. The trial was further amended to give 2 doses to all participants enrolled thereafter (n=22). Results were analyzed in modified intention-to-treat (mITT) on the randomized cohort (n=100) and Per Protocol (PP) on the whole cohort (n=167).

Results: Median age was 35 years, median CD4 count 649/µL, 16 missed M7 visit. In mITT, seroconversion was 97.7% for 2 doses and 97.9% for 3 doses, meeting the predefined non-inferiority criteria. At M7, antibodies titers against all vaccine genotypes were high in both groups (increase by 1.2-2.4 log10). There was no serious adverse event; participants with 3 doses experienced local reaction more frequently (82% versus 60% for 2 doses, p=0.027) with significantly more symptoms and longer duration.

Conclusions: In women with well-controlled HIV, 2 doses of HPV 9v-vaccine is non-inferior to 3 doses in terms of seroconversion and is associated with less reactogenicity.

Keywords: 9-valent vaccine; HIV; HPV; Women; immunogenicity.