HIV-infected individuals are at increased risk for human papillomavirus (HPV)-associated cancers. Quadrivalent HPV vaccine (qHPV) licensure studies were conducted in HIV-uninfected populations ≤26 yrs old with low exposure to HPV; qHPV is safe and immunogenic in HIV infected adults.
Phase 3, randomized, double-blind, placebo-controlled trial of qHPV in HIV-infected adults age 27 years and older with no previous HPV-associated cancer. Men were required to have a recent history of receptive anal sex. Participants had baseline assessments for anal and oral HPV (2 timepoints), anal cytology, and high resolution anoscopy (HRA). Participants received qHPV (or placebo) at entry, weeks 8 and 24. Anal HPV, cytology and oral HPV testing were obtained every 6 months. Treatment of HSIL and follow-up HRA was according to local standard of care. The primary endpoint was persistent anal HPV infection (or single detection at the final visit) in those without the infection at baseline. We hypothesized a 65% reduction with qHPV. The study was conducted at 23 US sites and 1 Brazil site. 99.9% confidence intervals are presented since the data are from a pre-specified DSMB review employing a Haybittle-Peto boundary of 0.001.
575 participants were enrolled (472 (82%) male, 103 (18%) women), 262 (46%) were white/non-Hispanic, 179 (31%) were black/non-Hispanic, 117 (20%) were Hispanic. Median age was 47 years [IQR 41-53], median CD4 602/µL [IQR 436-767], 83% had HIV RNA <50 copies/mL, 558 (97%) completed vaccination. With 2.1 years median follow-up, persistent anal HPV infection with qHPV types was 30% lower than hypothesized. Conditional power to show a significant difference in the primary endpoint was 7% should the study complete with similar event rates. Conditional power for detecting a difference in anal HSIL was <1%. The DSMB recommended stopping the trial due to futility. The qHPV was safe and well tolerated.
This study does not support HPV vaccination in older HIV-infected adults for prevention of new anal HPV infections or to improve HSIL treatment outcomes, but does suggest a trend for protection against oral infection. The role of qHPV for prevention of oral HPV infections should be further investigated. These results underscore the need for HPV vaccination prior to HPV exposure.