Department of Dermatology.
Division of Infectious Diseases, Department of Internal Medicine, Amsterdam Institute for Infection and Immunity (AII), Amsterdam UMC, University of Amsterdam.
AIDS. 2021 Sep 1;35(11):1753-1764. doi: 10.1097/QAD.0000000000002928.
Anal cancer precursor lesions high-grade anal intraepithelial neoplasia (HGAIN) are highly prevalent among HIV+ MSM. Treatment of HGAIN is frustrated by high recurrence rates. We investigated the efficacy of the quadrivalent human papillomavirus (qHPV) vaccine as posttreatment adjuvant in preventing HGAIN recurrence in HIV+ MSM.
Randomized, double-blind, placebo-controlled, multicentre trial.
Three HIV outpatient clinics in Amsterdam, the Netherlands.
HIV+ MSM with CD4+ cell count more than 350 cells/μl, biopsy-proven intra-anal HGAIN successfully treated in the past year, and lesions still in remission at enrolment, as assessed by high-resolution anoscopy (HRA).
Participants were randomized to three doses of qHPV (Gardasil-4, MSD) or placebo with vaccinations at 0, 2, and 6 months. HRA was repeated at 6, 12, and 18 months.
The primary outcome was cumulative, biopsy-proven HGAIN recurrence rate at 18 months, evaluated in an intention-to-treat (ITT) (received all vaccinations) and per-protocol analysis (all vaccinations and complete follow-up).
We randomized 126 participants of which 64 (50.8%) received qHPV and 62 (49.2%) placebo. All participants received three vaccinations, and in both groups for two participants follow-up was incomplete. We found no difference (P = 0.38) in cumulative HGAIN recurrence rates between the qHPV (44/64, 68.8%) and placebo group (38/62, 61.3%) in the ITT analysis [absolute risk reduction -7.5 (95% confidence interval (CI) -24.1 to 9.2)]. This was similar in the per-protocol analysis.
Despite adequate serological responses to qHPV vaccination, short-term recurrence of HGAIN was not prevented. These findings do not support qHPV vaccination as a treatment adjuvant to prevent HGAIN recurrence in HIV+ MSM.
肛门癌前病变高级别肛门上皮内瘤变（HGAIN）在 HIV+ 男男性行为者（MSM）中非常普遍。HGAIN 的治疗因高复发率而受阻。我们研究了四价人乳头瘤病毒（qHPV）疫苗作为治疗后的辅助手段，以预防 HIV+MSM 中 HGAIN 的复发。
随机、双盲、安慰剂对照、多中心试验。
荷兰阿姆斯特丹的三家 HIV 门诊诊所。
CD4+细胞计数大于 350 个/μl 的 HIV+MSM，过去一年成功治疗活检证实的肛门内 HGAIN，且在入组时通过高分辨率肛门镜（HRA）评估仍处于缓解期。
参与者被随机分配接受三剂 qHPV（加德西-4，默沙东）或安慰剂，疫苗接种分别在 0、2 和 6 个月进行。HRA 在 6、12 和 18 个月时重复进行。
主要结局是 18 个月时累积活检证实的 HGAIN 复发率，在意向治疗（ITT）（接受所有疫苗接种）和方案分析（所有疫苗接种和完整随访）中进行评估。
我们随机分配了 126 名参与者，其中 64 名（50.8%）接受了 qHPV 治疗，62 名（49.2%）接受了安慰剂治疗。所有参与者均接受了三剂疫苗接种，在两组中，有两名参与者的随访不完整。我们发现两组之间在 ITT 分析中累积 HGAIN 复发率没有差异（qHPV 组 44/64，68.8%；安慰剂组 38/62，61.3%；P=0.38）[绝对风险降低 -7.5（95%置信区间（CI）-24.1 至 9.2）]。方案分析中也类似。
尽管对 qHPV 疫苗接种有足够的血清学反应，但 HGAIN 的短期复发仍未得到预防。这些发现不支持 qHPV 疫苗接种作为预防 HIV+MSM 中 HGAIN 复发的治疗辅助手段。
