HIV-1 Superinfection Occurs Less Frequently Than Initial Infection in a Cohort of High-Risk Kenyan Women
| العنوان: | HIV-1 Superinfection Occurs Less Frequently Than Initial Infection in a Cohort of High-Risk Kenyan Women |
|---|---|
| المؤلفون: | Sandra Emery, R. Scott McClelland, Connor O. McCoy, Walter Jaoko, Frederick A. Matsen, Kishor Mandaliya, Julie Overbaugh, Katherine Odem-Davis, Keshet Ronen, Barbra A. Richardson, David F. Boyd |
| المصدر: | PLoS Pathogens PLoS Pathogens, Vol 9, Iss 8, p e1003593 (2013) |
| بيانات النشر: | Public Library of Science, 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Adult, Time Factors, QH301-705.5, Epidemiology, Immunology, Population, HIV Infections, HIV superinfection, medicine.disease_cause, Microbiology, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Immunodeficiency Viruses, Virology, Genetics, medicine, Humans, 030212 general & internal medicine, Biology (General), education, Molecular Biology, Biology, 030304 developmental biology, 0303 health sciences, education.field_of_study, business.industry, Proportional hazards model, Incidence (epidemiology), Incidence, Hazard ratio, virus diseases, RC581-607, biochemical phenomena, metabolism, and nutrition, Kenya, 3. Good health, Superinfection, Cohort, HIV-1, Medicine, Parasitology, Female, Immunologic diseases. Allergy, business, Cohort study, Research Article |
| الوصف: | 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 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. Author Summary 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. |
| اللغة: | English |
| تدمد: | 1553-7374 1553-7366 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::05631f7dafb9ef5235c2e982935fbb4f http://europepmc.org/articles/PMC3757054 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....05631f7dafb9ef5235c2e982935fbb4f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15537374 15537366 |
|---|