Abstract
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.
Highlights
Development of a safe and effective prophylactic HIV vaccine remains enormously challenging, due to the virus’s high diversity and our limited understanding of immune correlates of protection
HIV-infected individuals with continued exposure are at risk of acquiring a second infection, a process known as superinfection
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
Summary
Development of a safe and effective prophylactic HIV vaccine remains enormously challenging, due to the virus’s high diversity and our limited understanding of immune correlates of protection. A priority of HIV vaccine development is, to identify settings where natural infection elicits some immune functions desired in a vaccine. HIV-infected individuals who spontaneously control viral replication have provided insights into immune mechanisms of HIV control [1]. Models where the response, rather than delaying disease, prevents infection – the ultimate goal of a prophylactic vaccine – remain less well characterized. Studies of superinfection (reinfection from a different partner) provide a unique model in which to investigate the impact of pre-existing responses on susceptibility to infection by diverse circulating viral variants, which include multiple subtypes with up to 30% sequence variation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
