HIV-1 superinfection occurs less frequently than initial infection in a cohort of high-risk Kenyan women.
HIV-1 superinfection occurs less frequently than initial infection in a cohort of high-risk Kenyan women.
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DOI：
10.1371/journal.ppat.1003593
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发表时间：
2013
期刊：
影响因子：
6.7
通讯作者：
Overbaugh J
中科院分区：
文献类型：
--
作者：
Ronen K;McCoy CO;Matsen FA;Boyd DF;Emery S;Odem-Davis K;Jaoko W;Mandaliya K;McClelland RS;Richardson BA;Overbaugh J
HIV重复感染（再感染）在几种情况下都有报道，但没有研究设计和动力来严格比较其与初始感染的发生率。确定HIV感染是否降低了重复感染的风险，对于了解对自然HIV感染的免疫反应是否具有保护性至关重要。本研究比较了在肯尼亚蒙巴萨的高危妇女的前瞻性血清事件队列中初始感染和重复感染的发生率。开发了下一代基于测序的管道来筛选129名女性的双重感染。分析首次HIV感染后<6个月、>2年和一个干预时间的纵向血浆样本。对三个基因组区域中的扩增子进行测序，每个时间点每个基因获得901个序列的中位数。系统发育证据的多源性，证实了成对距离分析，定义重叠感染。通过对来自干预时间点的病毒进行测序来确定重复感染时间。这些数据与来自同一队列中另外17名女性的已发表数据相结合，共筛选了146名女性。确定了21例重叠感染，估计发病率为2.61/100人年（pys）。同期1910名妇女的初次感染率为5.75/100 pys。Andersen-Gill比例风险模型用于比较发病率，调整已知影响该队列中HIV易感性的协变量。重复感染发生率显著低于初始感染发生率，风险比为0.47（CI 0.29-0.75，p = 0.0019）。 这种较低的重复感染发生率仅在初始感染后>6个月观察到。这是第一个有充分把握的研究报告，艾滋病毒感染降低了再感染的风险，提高了对自然感染的免疫反应具有部分保护作用的可能性。重复感染风险随时间变化的观察结果意味着一个保护窗口，与艾滋病毒特异性免疫的成熟相一致。持续接触艾滋病毒的艾滋病毒感染者有二次感染的危险，这一过程被称为二次感染。在各种高危人群中都有重复感染的报道，但其发生频率仍不清楚。确定与初始感染相比的重复感染频率可以帮助澄清针对HIV产生的免疫反应是否可以防止再次感染-这是理解这种反应是否应该指导HIV疫苗设计的关键信息。在这项研究中，我们开发了一种灵敏的高通量方法来识别重复感染，并使用该方法对高危队列中的146名女性进行了重复感染筛查。这使我们能够通过比较该组的重叠感染发生率与较大队列中1910名妇女的初次感染发生率来确定首次HIV感染是否影响第二次感染的风险。我们发现，在控制了可能影响感染风险的行为和临床差异后，重复感染的发生率约为初始感染的一半。这些结果表明，在自然的HIV感染引起的免疫反应可能会提供部分保护，防止随后的感染，并表明设置的重叠感染可能揭示了保护性免疫反应的特点，并告知疫苗设计。
HIV superinfection (reinfection) has been reported in several settings, but no study has been designed and powered to rigorously compare its incidence to that of initial infection. Determining whether HIV infection reduces the risk of superinfection is critical to understanding whether an immune response to natural HIV infection is protective. This study compares the incidence of initial infection and superinfection in a prospective seroincident cohort of high-risk women in Mombasa, Kenya. A next-generation sequencing-based pipeline was developed to screen 129 women for superinfection. Longitudinal plasma samples at <6 months, >2 years and one intervening time after initial HIV infection were analyzed. Amplicons in three genome regions were sequenced and a median of 901 sequences obtained per gene per timepoint. Phylogenetic evidence of polyphyly, confirmed by pairwise distance analysis, defined superinfection. Superinfection timing was determined by sequencing virus from intervening timepoints. These data were combined with published data from 17 additional women in the same cohort, totaling 146 women screened. Twenty-one cases of superinfection were identified for an estimated incidence rate of 2.61 per 100 person-years (pys). The incidence rate of initial infection among 1910 women in the same cohort was 5.75 per 100pys. Andersen-Gill proportional hazards models were used to compare incidences, adjusting for covariates known to influence HIV susceptibility in this cohort. Superinfection incidence was significantly lower than initial infection incidence, with a hazard ratio of 0.47 (CI 0.29–0.75, p = 0.0019). This lower incidence of superinfection was only observed >6 months after initial infection. This is the first adequately powered study to report that HIV infection reduces the risk of reinfection, raising the possibility that immune responses to natural infection are partially protective. The observation that superinfection risk changes with time implies a window of protection that coincides with the maturation of HIV-specific immunity. HIV-infected individuals with continued exposure are at risk of acquiring a second infection, a process known as superinfection. Superinfection has been reported in various at-risk populations, but how frequently it occurs remains unclear. Determining the frequency of superinfection compared with initial infection can help clarify whether the immune response developed against HIV can protect from reinfection – critical information for understanding whether such responses should guide HIV vaccine design. In this study, we developed a sensitive high-throughput method to identify superinfection and used this to conduct a screen for superinfection in 146 women in a high-risk cohort. This enabled us to determine if first HIV infection affects the risk of second infection by comparing the incidence of superinfection in this group to the incidence of initial infection in 1910 women in the larger cohort. We found that the incidence of superinfection was approximately half that of initial infection after controlling for behavioral and clinical differences that might affect infection risk. These results suggest that the immune response elicited in natural HIV infection may provide partial protection against subsequent infection and indicate the setting of superinfection may shed light on the features of a protective immune response and inform vaccine design.
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影响因子：
1
作者：
Chohan, Bhavna H.;Piantadosi, Anne;Overbaugh, Julie
通讯作者：
Overbaugh, Julie
影响因子：
3.3
作者：
Basu D;Kraft CS;Murphy MK;Campbell PJ;Yu T;Hraber PT;Irene C;Pinter A;Chomba E;Mulenga J;Kilembe W;Allen SA;Derdeyn CA;Hunter E
通讯作者：
Hunter E
影响因子：
6.7
作者：
Piantadosi A;Chohan B;Chohan V;McClelland RS;Overbaugh J
通讯作者：
Overbaugh J
影响因子：
5.4
作者：
Blish, Catherine A.;Dogan, Ozge C.;Overbaugh, Julie
通讯作者：
Overbaugh, Julie
影响因子：
64.8
作者：
Altfeld, M;Allen, TM;Walker, BD
通讯作者：
Walker, BD