Immunogenicity of 2 versus 3 dose HPV vaccination by HIV infection status in Eswatini

BACKGROUND: There are limited immunogenicity data among people with HIV (PWH) following human papilloma virus (HPV) vaccination, particularly with fewer dose schedules. We compared immunogenicity of 9-valent HPV vaccine (9vHPV) by HIV infection status in Eswatini. METHODS: In this multi-site, open-label, non-inferiority study, three PWH cohorts received 2-doses of 9vHPV at 0 and 6 months: 1) boys 9-14 years (n = 349); 2) girls 9-14 years (n = 352); 3) adolescent girls and young women (AGYW) 15-26 years (n = 350). A comparison cohort of AGYW without HIV received the reference standard 3-dose regimen at 0, 2 and 6 months. At 7 months, we measured HPV-6/11/16/18/31/33/45/52/58 antibodies by competitive Luminex Immunoassay. We assessed non-inferiority of anti-HPV geometric mean titer ratios (GMTR), lower-bound 95% confidence interval > 0.5, among PWH versus AGYW without HIV; and secondarily explored GMTRs by HIV viral load (VL) at baseline or 7 months. RESULTS: PWH 2-dose completion was high: 95% boys, 97% girls and 93% AGYW. Among AGYW without HIV, 95% received the second dose and 84% completed the 3-doses. GMTR of boys and girls with HIV were non-inferior to AGYW without HIV for all HPV subtypes: boys ranged from 0.74 (0.60, 0.90) for HPV-45 to 1.30 (1.08, 1.56) for HPV-58; girls ranged from 0.70 (0.58, 0.86) for HPV-45 to 1.32 (1.10, 1.58) for HPV-58. GMTR of AGYW with HIV were non-inferior to AGYW without HIV for all subtypes except HPV-45; ranging from 0.66 (0.54, 0.81) for HPV-18 to 0.95 (0.78, 1.14) for HPV-11, and (0.40, 0.60) for HPV-45. Among PWH with VL > 50 copies/mL, titers for all HPV sub-types were lower, and GMTRs were not non-inferior. CONCLUSION: We found overall non-inferior immunogenicity of 2-dose 9vHPV among PWH versus 3-doses in AGYW without HIV, but 2-dose immunogenicity among viremic PWH may be compromised. Resource-saving 2-dose vaccination is an appropriate option for PWH while sustaining their VL suppression. TRIAL REGISTRATION NUMBER: clinicaltrials.govNCT04982614.