Effectiveness Of The Quadrivalent HPV Vaccine Against Anal ≥HSILs In A Spanish Population Of HIV+ MSM Aged >26 Years

Background: Anal squamous cell carcinoma is the most frequent virus-related non-AIDS-defining neoplasia among HIV-infected individuals, especially MSM. The objectives of this study were: to analyze the effectiveness of the quadrivalent HPV (qHPV) vaccine to prevent anal ≥ high-grade squamous intraepithelial lesions (≥HSILs), external ano-genital lesions (EAGLs), and infection by qHPV vaccine genotypes in HIV+ MSM; and to study the immunogenicity of the vaccine and risk factors for ≥HSILs Methods: : This study is nested within a randomized, double-blind, placebo-controlled trial of the qHPV vaccine, which enrolled participants between May 2012 and May 2014, with a 48-month follow-up. Vaccine or placebo was administered at 0, 2, and 6 months, and vaccine antibody titers were evaluated at 7, 12, 24, 36, and 48 months. Data were gathered at 12, 24, 36, and 48 months on sexual habits, CD4/CD8 cell/counts, HIV viral load, and the results of cytology (Thin Prep® Pap Test), HPV PCR genotyping (Linear Array HPV Genotyping Test), and high-resolution anoscopy (Zeiss 150 fc © colposcope). Results: : The study included 129 patients, 66 (51.2%) in vaccine arm and 63 (48.4%) in placebo arm. The vaccine and placebo groups did not differ in ≥ HSILs (14.1 vs. 13.1%, respectively, p=0.98) or EAGL (14.3 vs. 13.6%, p=0.98) rates during follow-up; however, a protective effect against HPV 6 was observed during the first year of follow-up in the vaccine versus placebo group (7.5% vs. 23.4%; p=0.047). A between-arm difference (p=0.0001) in antibody formation was observed at 7 months (76.9% in vaccine arm vs . 30.2% in placebo arm), 12 months (68.1% vs . 26.5%), 24 months (75% vs . 32.5%), 36 months (90% vs . 24.4%), and 48 months (87.2% vs . 30%). Finally, receipt of the full vaccine 6 months earlier was a risk factor for ≥ HSIL (82.4% vs . 17.6%, OR 0.869 [95% CI 0.825-0.917]). Conclusions: Vaccine and placebo arms did not significantly differ in ≥HSIL or EAGL rates or in protection against infection by HPV genotype vaccine except for HPV6 at 12 months after the first dose. A long-lasting immune response was observed in almost all of the vaccinated men. The main protective factor against ≥ HSIL was to have completed the vaccination regimen more than 6 months earlier.Clinical trial registration: ISRCTN14732216 (http://www.isrctn.com/ISRCTN14732216)