四价人乳头瘤病毒（qHPV）疫苗在西班牙男男性行为者（MSM）HIV阳性人群中的安全性和免疫原性。
Safety and immunogenicity of the quadrivalent human papillomavirus (qHPV) vaccine in HIV-positive Spanish men who have sex with men (MSM).
作者信息
Hidalgo-Tenorio Carmen, Ramírez-Taboada Jessica, Gil-Anguita Concepción, Esquivias Javier, Omar-Mohamed-Balgahata Mohamed, SamPedro Antonio, Lopez-Ruz Miguel, Pasquau Juan
机构信息
Infectious Disease Service, University Hospital Virgen de las Nieves, Granada, Spain.
Pathology Service, University Hospital Virgen de las Nieves, Granada, Spain.
出版信息
AIDS Res Ther. 2017 Jul 18;14(1):34. doi: 10.1186/s12981-017-0160-0.
BACKGROUND
Safety and immunogenicity of the quadrivalent human papillomavirus (qHPV) vaccine were evaluated in HIV-positive Spanish MSM. The prevalence of High Squamous Intraepithelial Lesions (HSIL) and genotypes of high-risk human papillomavirus (HR-HPV) were also determined, as well as risk factors associated with the presence of HR-HPV in anal mucosa.
METHODS
This is a randomised, double blind, placebo-controlled trial of the quadrivalent HPV (qHPV) vaccine. The study enrolled from May 2012 to May 2014. Vaccine and placebo were administered at 0, 2 and 6 months (V1, V2, V3 clinical visits). Vaccine antibody titres were evaluated at 7 months. Cytology (Thin Prep Pap Test), HPV PCR genotyping (Linear Array HPV Genotyping Test), and high-resolution anoscopy (Zeiss 150 fc© colposcope) were performed at V1.
RESULTS
Patients (n = 162; mean age 37.9 years) were screened for inclusion; 14.2% had HSIL, 73.1% HR-HPV and 4.5% simultaneous infection with HPV16 and 18. Study participants (n = 129) were randomized to qHPV vaccine or placebo. The most common adverse event was injection-site pain predominating in the placebo group [the first dose (83.6% vs. 56.1%; p = 0.0001]; the second dose (87.8% vs. 98.4%; p = 0.0001); the third dose (67.7% vs. 91.9%; p = 0.0001). The vaccine did not influence either the viral load of HIV or the levels of CD4. Of those vaccinated, 76% had antibodies to HPV vs. 30.2% of those receiving placebo (p = 0.0001). In the multivariate analysis, Older age was associated with lower HR-HPV infection (RR 0.97; 95% CI 0.96-0.99), and risk factor were viral load of HIV >200 copies/µL (RR 1.42 95% CI 1.17-1.73) and early commencement of sexual activity (RR 1.35; 95% CI 1.001-1.811).
CONCLUSIONS
This trial showed significantly higher anti-HR-HPV antibody titres in vaccinated individuals than in unvaccinated controls. There were no serious adverse events attributable to the vaccine. In our cohort, 1 of every 7 patients had HSIL and the prevalence of combined infection by genotypes 16 and 18 was low. This suggests that patients could benefit from receiving qHPV vaccine. Older age was the main protective factor against HR-HPV infection, and non-suppressed HIV viremia was a risk factor.
CLINICAL TRIAL REGISTRATION
ISRCTN14732216 ( http://www.isrctn.com/ISRCTN14732216 ).
背景
评估四价人乳头瘤病毒（qHPV）疫苗在西班牙HIV阳性男男性行为者中的安全性和免疫原性。还确定了高度鳞状上皮内病变（HSIL）的患病率、高危型人乳头瘤病毒（HR-HPV）的基因型，以及与肛门黏膜中HR-HPV存在相关的危险因素。
方法
这是一项四价人乳头瘤病毒（qHPV）疫苗的随机、双盲、安慰剂对照试验。研究于2012年5月至2014年5月招募患者。疫苗和安慰剂分别在0、2和6个月（V1、V2、V3临床访视）接种。在7个月时评估疫苗抗体滴度。在V1时进行细胞学检查（薄层液基细胞学检测）、HPV PCR基因分型（线性阵列HPV基因分型检测）和高分辨率肛门镜检查（蔡司150 fc©阴道镜）。
结果
共筛查了162例患者（平均年龄37.9岁）纳入研究；14.2%有HSIL，73.1%有HR-HPV，4.5%同时感染HPV16和18。129例研究参与者被随机分为qHPV疫苗组或安慰剂组。最常见的不良事件是注射部位疼痛，安慰剂组更为突出[第一剂（83.6%对56.1%；p = 0.0001）；第二剂（87.8%对98.4%；p = 0.0001）；第三剂（67.7%对91.9%；p = 0.0001）]。疫苗对HIV病毒载量或CD4水平均无影响。接种疫苗者中，76%产生了HPV抗体，而接受安慰剂者中这一比例为30.2%（p = 0.0001）。多因素分析显示，年龄较大与HR-HPV感染率较低相关（风险比0.97；95%置信区间0.96 - 0.99），危险因素包括HIV病毒载量>200拷贝/µL（风险比1.42，95%置信区间1.17 - 1.73）和较早开始性行为（风险比1.35；95%置信区间1.001 - 1.811）。
结论
该试验表明，接种疫苗个体的抗HR-HPV抗体滴度显著高于未接种疫苗的对照。没有可归因于疫苗的严重不良事件。在我们的队列中，每7名患者中有1例患有HSIL，16和18型合并感染的患病率较低。这表明患者可能从接种qHPV疫苗中获益。年龄较大是预防HR-HPV感染的主要保护因素，而未受抑制的HIV病毒血症是一个危险因素。
临床试验注册
ISRCTN14732216（http://www.isrctn.com/ISRCTN14732216）
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