Rationale and design of a clinical trial of a reduced dosing schedule for the nonavalent human papillomavirus vaccine in women living with HIV: The NOVA-HIV study.

Abstract

Virtually all cases of cervical cancer are caused by human papillomavirus (HPV). Women and people with a cervix living with HIV (women with HIV) are disproportionately impacted by cervical cancer; they experience higher rates of HPV infection and increased susceptibility to persistent HPV infection than women without HIV. HPV vaccination is highly effective for prevention of cervical cancer, and the World Health Organization currently recommends a one or two-dose HPV vaccination schedule for immunocompetent females. Although the approved nonavalent HPV (9vHPV) vaccine is highly safe, immunogenic, and efficacious in those without HIV, there are very few data in women with HIV. To address this knowledge gap, the NOVA-HIV study is designed as a Canadian multicenter, observer-blind, randomized, phase IV clinical trial of the 9vHPV vaccine in women with HIV aged 18-45 years. The primary objective is to determine whether peak anti-HPV16/18 geometric mean titers (GMTs) after two doses of 9vHPV vaccine are non-inferior to peak anti-HPV16/18 GMTs after three doses. The trial will enroll 275 women with HIV from 11 sites across five Canadian provinces. Participants are randomized 1:1 to receive the 9vHPV vaccine at the routine schedule (0/2/6 months) or extended schedule (0/6/12 months). Over 24 months, participants attend six or seven visits, where clinical data, blood, and vaginal samples are collected. Data generated could support the implementation of reduced-dose schedules in women with HIV, making vaccination more feasible, contributing to the elimination of cervical cancer, and accelerating global health equity.