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Quadrivalent HPV Vaccine Elicits Antibody
and Cell Responses in HIV+ Teens, Young Adults
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20th International AIDS Conference, July 20-25, 2014, Melbourne
Mark Mascolini
Three doses of the quadrivalent human papillomavirus (HPV) vaccine generated antibody and cell-mediated immune responses in HIV-positive and matched negative adolescents and young adults, according to results of nonrandomized, open-label trial [1]. The findings add to data showing that the vaccine generates good antibody responses and HPV seroconversion rates in young and middle-aged HIV-positive women and in children with HIV [2-4].
HPV, the most prevalent sexually transmitted infection worldwide, can cause cervical cancer, anal cancer, and other cancers. Cervical and anal HPV rates are especially high in HIV-positive people, and the risk of HPV-related cancer rises with a falling CD4 count. Three previous trials in children with HIV and in young and middle-aged HIV-positive women demonstrated the safety and immunogenicity of a standard three-dose course of the quadrivalent HPV vaccine, which targets HPV types 6, 11, 16, and 18 [2-4]. US guidelines recommend HPV vaccination of HIV-positive people from 11 to 26 years old regardless of CD4 count [5].
To further the understanding of quadrivalent HPV vaccine immunogenicity and safety in antiretroviral-treated adolescents and young adults, Italian investigators planned a national 18-month nonrandomized, open-label trial, protocol NCT01512784 [1,6]. Researchers recruited clinically asymptomatic 13- to 26-year-old males and females taking antiretroviral therapy for at least 10 years and with two viral loads below 37 copies in the past 6 months and a CD4 count above 350. They excluded people with a history of HPV-related anogenital warts or genital lesions, those with other chronic diseases, and those with drug or alcohol dependence.
The investigators matched 46 HIV-positive study participants to 47 healthy HIV-negative controls by age and gender. All study participants received the standard three-dose course of the quadrivalent HPV vaccine (at 0, 2 and 6 months). The researchers collected serum samples at enrollment and 1 month after each vaccine dose for up to 18 months. They evaluated immunogenicity by measuring HPV-specific antibody titers, and they evaluated vaccine-induced cell-mediated immunity by analyzing T-cell patterns, immune activation state, and cytokine responses.
IgG titers reflecting antibody responses against HPV types targeted by the vaccine rose through 3 months at virtually identical rates in HIV-positive participants and HIV-negative controls and peaked at 7 months. Titers declined in both groups at 12 months (6 months after the last dose) to about month-3 levels then remained stable through 18 months. Throughout follow-up, antibody levels were slightly but not significantly lower in the HIV group than in controls.
Percentage of activated CD4 and CD8 cells rose significantly at 3 and 7 months in both the HIV-positive and negative groups. Seven-month responses were significantly greater in HIV-positive participants than in controls for CD4+CD25+HLA-DRII+ cells (P = 0.004) and for CD8+CD25+HLA-DRII+ cells (P = 0.003).
Levels of HPV-specific IL-2-secreting CD4 cells rose significantly at month 3 in both the HIV-positive and negative groups then declined modestly at month 7 but remained above baseline values. HPV-specific interferon-gamma-secreting CD4 cells rose significantly in both groups at month 3 and remained significantly higher than baseline at month 7. HPV-specific interferon-gamma- and TNF-alpha-secreting CD8 cells rose significantly in both groups at month 3 and remained significantly elevated at month 7. Perforin and granzyme B production also rose significantly in CD8 cells of both groups.
Among HIV-positive study participants, CD4 counts remained stable through 18 months of follow-up, while CD4 percent rose slightly over time. About 90% of HIV-positive participants had an undetectable HIV load both at baseline and 18 months.
Injection site reactions and mild systemic symptoms (fever, malaise, headache) accounted for most adverse events, which affected a slightly higher proportion of HIV-positive study participants. Injection site pain, the most frequent adverse event, affected 33% of the HIV group and 19% of the control group. Headache, the most frequent systemic adverse events, affected 13.5% with HIV and 2% without HIV. There were no severe or life-threatening adverse events.
The researchers concluded that the quadrivalent vaccine generated durable antibody responses against targeted HPV types and stimulated cell-mediated immunity to a similar degree in HIV-positive and negative adolescents and young adults. They believe these findings support current recommendations to vaccinate youngsters and young adults with HIV.
References
1. Rainone V, Trabattoni D, Penagini F, et al. Efficacy of HPV vaccination in HIV+ adolescents and young adults for the induction of strong HPV-specific humoral and cell-mediated immune responses. AIDS 2014. 20th International AIDS Conference. July 20-25, 2014. Melbourne. Abstract WEAB0101.
2. Kahn JA, Xu J, Kapogiannis BG, et al. Immunogenicity and safety of the human papillomavirus 6, 11, 16, 18 vaccine in HIV-infected young women. Clin Infect Dis. 2013;57:735-744. http://www.ncbi.nlm.nih.gov/pubmed/23667266
3. Kojic EM, Kang M, Cespedes MS, et al. Immunogenicity and safety of the quadrivalent human papillomavirus vaccine in HIV-1-infected women. Clin Infect Dis. 2014;Apr 9;pii:ciu238. http://www.ncbi.nlm.nih.gov/pubmed/24723284
4. Levin MJ1, Moscicki AB, Song LY, et al. Safety and immunogenicity of a quadrivalent human papillomavirus (types 6, 11, 16, and 18) vaccine in HIV-infected children 7 to 12 years old. J Acquir Immune Defic Syndr. 2010;55:197-204. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3033215/
5. Centers for Disease Control and Prevention. Human papillomavirus (HPV) ACID vaccine recommendations. http://www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/hpv.html
6. ClinicalTrials.gov. Long term immunogenicity of quadrivalent human papillomavirus vaccine (Gardasil) in HIV-infected adolescents and young adults. http://clinicaltrials.gov/ct2/show/NCT01512784
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