Immunological and genetic correlates of delayed HIV disease progression in children with perinatally-acquired HIV-1 infection, Harare, Zimbabwe.

全世界约300万感染艾滋病毒的儿童中有90%生活在撒哈拉以南非洲。虽然在抗逆转录病毒治疗前，预计只有50%的围产期感染儿童能存活到两岁以上，但最近来自南部非洲区域的报告显示，越来越多的青少年感染了未经治疗的垂直获得性艾滋病毒。这项研究的目的是调查免疫和遗传相关的长期围产期获得性艾滋病毒感染在最近确定的一组青少年在哈拉雷，津巴布韦。这些年龄较大的儿童在生命早期没有被诊断出来，因此为探索人类免疫系统与延迟HIV疾病进展相关的潜在机制提供了机会。研究表明，与健康对照相比，HIV-1感染的青少年长期幸存者中某些HLA等位基因丰富，但在这一非洲儿童队列中，其他基因变异在延迟HIV-1疾病进展中的作用知之甚少。参与MHC I类肽装载复合物的蛋白变体或其他基因（如杀伤细胞免疫球蛋白样受体（KIR））的变体的表达可能在HIV-1感染的长期控制中发挥作用，应该进行研究，以建立与HIV长期存活相关的宿主遗传学图谱。确定和了解免疫保护与艾滋病毒感染之间的相互关系，有可能有助于设计疫苗和治疗方法，以对抗感染和疾病。这在世界上艾滋病毒负担最重的发展中区域尤其重要。

Ninety-percent of some 3 million HIV-infected children worldwide live in Sub-Saharan Africa. Although only 50% of perinatally-infected children were expected to survive beyond two years of age in the pre-antiretroviral therapy (ART) era, recent reports from the Southern Africa region describe a growing population of adolescents living with untreated vertically-acquired HIV infection. This study aims to investigate the immunological and genetic correlates associated with long-standing perinatally-acquired HIV infection in a recently-identified group of adolescents in Harare, Zimbabwe. These older children were not diagnosed early in life and so provide an opportunity to explore the underlying mechanisms of the human immune system related to delayed HIV disease progression.Studies have shown an enrichment of certain HLA alleles in adolescent long-term survivors of HIV-1 infection compared to healthy controls, but little is known about the role of other gene variants in delayed HIV-1 disease progression in this cohort of African children. The expression of protein variants involved in the peptide-loading complex of MHC class I or variants of other genes such as killer-cell immunoglobulin-like receptors (KIR) may play a role in long-term control of HIV-1 infection and should be investigated to build a picture of the host genetics which correlate with long-term survival of HIV. Defining and understanding the correlates of immune protection to HIV infection has the potential to aid in the design of vaccine and therapeutics to combat infection and disease. This is particularly important in developing regions of the world where the burden of HIV is highest.