Long-term immunogenicity and efficacy of the quadrivalent human papillomavirus vaccine in women with HIV: a longitudinal cohort study.

Background

Understanding the impact of the human papillomavirus (HPV) vaccine in women with HIV, who have higher rates of HPV infection and associated disease, is vital to achieving cervical cancer elimination. We aimed to assess the immunogenicity and efficacy of the quadrivalent HPV (qHPV) vaccine up to 9 years in a cohort of women with HIV.

Methods

This longitudinal multicentre cohort study recruited girls and women with HIV aged 9 years and older from 14 clinics providing HIV and gynaecological care across Canada. Participants were administered three doses of qHPV vaccine at 0, 2, and 6 months and followed up from July 1, 2008, to June 27, 2019. Clinical data, anti-HPV serology, liquid-based cervical cytology, and HPV DNA genotyping were conducted at baseline and every 6-12 months. Immunogenicity endpoints were anti-HPV geometric mean titres (GMTs) and seropositivity rates. We assessed the effect of time-varying HIV parameters on time to seroreversion with extended Cox regression models. GMTs for an age-restricted subset (24-45 years) were compared with a published cohort with one-sample t tests. Efficacy endpoints were the incidence of persistent qHPV, genital warts, and cervical intraepithelial neoplasia of grade two and higher (CIN2+).

Findings

There were 228 participants in the per-protocol population, with a median age at baseline of 38·5 years (IQR 32·0-45·4), median CD4 count of 499·5 (IQR 380·8-700·0) cells per μL, and 160 (70·2%) participants had suppressed HIV viral loads (<50 copies per mL). Median follow-up was 5·9 years (IQR 2·3-7·7). In the per-protocol population, following very high seroconversion rates at month 7, during follow-up there were 18 (13·6%) of 132 seroreversions for HPV6, 22 (11·8%) of 186 for HPV11, 12 (8·5%) of 141 for HPV16, and 60 (36·4%) of 165 for HPV18. Peak antibody titres and serial HIV viral load were significant predictors of time to seroreversion. Anti-HPV GMTs were similar between women with and without HIV (historical comparator group) for up to 9 years. In the per-protocol population, the incidence of persistent qHPV was 0·52 (95% CI 0·22-1·10) per 100 person-years, the incidence of genital warts was 0·37 (0·12-0·87) per 100 person-years, and the incidence of CIN2+ was 0·00 (0·00-0·24) per 100 person-years.

Interpretation

These data show low rates of infection and disease in this vaccinated cohort of women with HIV. Continual HIV viral load suppression after vaccination is important to ensure continued protection.

Funding

Canadian Institutes for Health Research (CIHR), CIHR Canadian HIV Trials Network, and in-kind contribution from Merck Canada.