Cellerai Cristina, Little Susan J, Loes Sabine Kinloch-de
Department of Immunology and Molecular Pathology, University College London, Royal Free Hospital Campus, London NW3 2QG, UK.
Curr Opin HIV AIDS. 2008 Jan;3(1):67-74. doi: 10.1097/COH.0b013e3282f31d4b.
Treatment of primary HIV-1 infection may alter the natural history of HIV-1 infection and delay the need for chronic antiretroviral therapy; it may also be a public health measure. We discuss the results of therapeutic trials and cohort studies, the occurrence of transmitted drug resistance, and recent findings in terms of immunopathogenesis and decay of viral reservoirs.
Events at the time of primary HIV-1 infection are understood to set the scene for persistence of immunologic damage and chronic immune activation, with a rapid viral onslaught primarily on memory CD4 T cells at mucosal effector sites. The initiation of antiretroviral therapy at primary HIV-1 infection has been associated with a high degree of undetectable viremia in compliant patients and substantial decay of reservoirs in peripheral blood. The degree of immune reconstitution at the gut mucosal level, however, does not appear to be comparable to that in peripheral blood.
Recent insights into the long-term consequences of the early burst of HIV-1 replication - together with transmitted drug resistance, onward transmission, and the possibility of decay of viral reservoirs - are important steps in helping to design future therapeutic strategies in primary HIV-1 infection in an era of intense drug and vaccine development.
治疗原发性HIV-1感染可能改变HIV-1感染的自然史并推迟慢性抗逆转录病毒治疗的需求;它也可能是一项公共卫生措施。我们讨论了治疗试验和队列研究的结果、传播耐药性的发生情况,以及在免疫发病机制和病毒储存库衰减方面的最新发现。
原发性HIV-1感染时发生的事件被认为是免疫损伤持续和慢性免疫激活的基础,病毒主要在黏膜效应部位对记忆性CD4 T细胞进行快速攻击。在原发性HIV-1感染时开始抗逆转录病毒治疗与依从性好的患者中高度不可检测的病毒血症以及外周血中储存库的大量衰减有关。然而,肠道黏膜水平的免疫重建程度似乎与外周血中的情况不可比。
对HIV-1复制早期爆发的长期后果的最新认识——连同传播耐药性、进一步传播以及病毒储存库衰减的可能性——是在药物和疫苗大力研发的时代帮助设计原发性HIV-1感染未来治疗策略的重要步骤。