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  21st Conference on Retroviruses and
Opportunistic Infections
Boston, MA March 3 - 6, 2014
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Quadrivalent HPV Vaccine Induces Immune Memory in US Men With HIV
  CROI 2014, March 3-6, 2014, Boston
Mark Mascolini
Concentrations of antibodies against four human papillomavirus (HPV) types covered by the quadrivalent vaccine dropped then stabilized in the 2 years after vaccination in a study US men with HIV infection [1]. But antibody responses rebounded after challenge with another vaccine dose, a finding indicating that quadrivalent HPV vaccination creates protective immune memory in men with HIV.
HPV infection can lead to anal cancer and other cancers in men, and HIV-positive men run a high risk of anal cancer, even when taking antiretroviral therapy. Gardasil, a quadrivalent vaccine against HPV types 6, 11, 16, and 18, is licensed in the United States and elsewhere for boys, girls, and young men and women to protect them from HPV-related cancers (including cervical cancer in women) and genital warts. HPV-16 and 18 are the prime causes of anal and cervical cancer, while HPV-6 and 11 cause most warts.
Previous work established the safety and immunogenicity of the quadrivalent vaccine in men with HIV [2]. US researchers conducted this study to assess the duration and quality of vaccine-induced immune responses in HIV-positive men.
This analysis involved HIV-positive men enrolled in the reported single-arm trial [2]. These men all received the standard three-dose vaccination at weeks 0, 8, and 24. Seventy-five men agreed to a fourth dose 2 to 2.5 years after the third dose. The investigators measured serum antibody concentrations against the four vaccine-covered HPV types just before the fourth dose, then 1 and 4 weeks later.
Most men, 63%, were white, 16% Hispanic, and 13% black. Median age stood at 47 and median CD4 count at 517 (nadir 220). Most men, 83%, had a viral load below 200 copies, and most were taking antiretroviral therapy. Seventy-three men had evaluable sera at week 128 (just before the fourth dose), 67 at week 129, and 69 at week 132.
Before the first vaccine dose, 39% of men were seropositive for HPV-6 antibodies, 30% for HPV-11, 26% for HPV-16, and 18% for HPV-18. At week 28, 4 weeks after the third dose, respective seropositivity rates were 97%, 98%, 99%, and 96%. By week 128 those rates had waned to 94%, 96%, 94%, and 64%. After the fourth dose, at week 129, seropositivity rates rebounded to 95%, 100%, 98%, and 91%. By week 132 those rates reached 100%, 100%, 100%, and 94%. Compared with week 28, antibody concentrations at week 132 were significantly higher for HPV-16 (P = 0.003) and HPV-18 (P = 0.001)--the two cancer-causing types--but not for types 6 or 11.
The researchers concluded that anti-HPV antibodies dropped in the first year after the three-dose vaccination series, stabilized 1 to 2 years after vaccination, and rebounded after a fourth dose. They believe this pattern "suggests the development of immune memory, which often correlates with long-lasting protection for other vaccines." In other words, the quadrivalent vaccine appears to confer long-lasting protection against cancer-causing HPV types in HIV-positive men, even after antibody concentrations drop following a standard three-dose series.
ACTG A5298, a phase 3, randomized, placebo-controlled trial, will test HPV vaccination in HIV-positive men and women 27 years old or older. The primary endpoint is persistent anal infection with vaccine types (clinicaltrials.gov identifier NCT01461096).
US guidelines recommend the quadrivalent vaccine for HIV-positive people 9 to 26 years old and, indeed, for everyone in that age range.
Link to webcast:
1. Wilkin T, Lensing S, Einstein M, Lee J, et al. Quadrivalent HPV vaccine demonstrates immune memory in HIV-1-infected men. CROI 2014. Conference on Retroviruses and Opportunistic Infections. March 3-6, 2014. Boston. Abstract 102.
2. Wilkin T, Lee JY, Lensing SY, et al. Safety and immunogenicity of the quadrivalent human papillomavirus vaccine in HIV-1-infected men. J Infect Dis. 2010;202:1246-1253. http://jid.oxfordjournals.org/content/202/8/1246.long