Dissecting the influence of HIV infection and treatment with antiretroviral therapy on Human Papillomavirus infection, disease and immunity: Designing new tools for therapeutic intervention.

抗逆转录病毒治疗（ART）的HIV+女性中HPV感染相关宫颈病变的增加和加速的癌变意味着HIV诱导的HPV特异性免疫应答的失调增加了HR HPV复制，降低HPV清除率，从而增加进展为轻度和中度异型增生的风险，即使在ART的存在下。存在中度宫颈不典型增生的妇女促进统计学上更频繁的HPV DNA整合事件进入宿主基因组。我们假设HPV病毒整合是驱动HIV+女性快速癌变的关键事件。治疗性HPV疫苗可能能够恢复HPV特异性适应性免疫，以根除持续的HPV感染，从而预防ART中HIV+个体的HPV疾病进展。2H研究旨在阐明ART时代HIV，免疫系统和HPV诱导的致癌作用之间复杂的相互作用。

The increase of HPV infection associated cervical lesions and accelerated carcinogenesis in HIV+ women of antiretroviral therapy (ART) implies that HIV-induced dysregulation of the HPV-specific immune response increases HR HPV replication, reduces HPV clearance and consequently increases the risk of progression to mild and moderate dysplasia even in the presence of ART. We postulate that higher HR HPV loads in HIV+ women in the presence of moderate cervical dysplasia facilitate statistically more frequent HPV DNA integration events into the host genome. We hypothesize that HPV viral integration is the key event in driving rapid cancerogenesis in HIV+ women. A therapeutic HPV vaccine might be able to resurrect HPV-specific adaptive immunity to erradicate persistent HPV infection and hence prevent HPV disease progression in HIV+ individuals on ART. The 2H study aims to elucidate the complicated interplay between HIV, the immune system and HPV induced carcinogenesis in the era of ART.