Abstract

HIV-1 dual infection occurs when an individual is simultaneously or sequentially infected with two or more genetically distinct HIV-1 strains. According to the number of infected strains, HIV-1 dual infection can be divided in double infection and triple infection and so on. Currently, the majority of dual infection cases have been reported to be double infections which can result in detrimental clinical outcomes. The high incidence of double infection among specific high-risk populations increases the likelihood of triple infection, which has been sporadically described. There is no doubt that we are concerned about the association between triple infection and disease progression. However, this relationship is still unclear on the population level. In this study, 70 individuals from the Beijing PRIMO cohort were longitudinally followed up with a median time of 15.75 months for the purpose of investigating the incidence of dual infection. Phylogenetic analyses using bulk and single-genome sequences showed that nine individuals acquired double infection, with the incidence of 9.21 per 100 person-years, and three individuals with triple infection were identified, with the incidence of 3.07 per 100 person-years. The further survival analysis demonstrated that the triple infection group exhibited faster CD4+ T-cell decline. In summary, these results demonstrate for the first time that the triple HIV-1 infection might reduce CD4+ T-cell counts, which would predict a more rapid disease progression.

Highlights

  • Human immunodeficiency virus type 1 (HIV-1) exhibits high genetic diversity and a formidable pattern of evolution (McCutchan et al, 1996), which is driven in large part by the high mutation and recombination rates of the reverse transcriptase enzyme

  • Among the individuals participating in the Beijing PRIMO cohort between March 2010 and November 2011, 70 individuals meeting the inclusion criteria were enrolled in this study

  • Bulk viral sequence analysis, single-genome amplification (SGA) and next-generation sequencing assays (NGS) are the three diagnostic strategies that are widely used for detection (Jurriaans et al, 2008; Sheward et al, 2015; Hebberecht et al, 2018; Popescu et al, 2018)

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Summary

Introduction

Human immunodeficiency virus type 1 (HIV-1) exhibits high genetic diversity and a formidable pattern of evolution (McCutchan et al, 1996), which is driven in large part by the high mutation and recombination rates of the reverse transcriptase enzyme. The emerging CRFs and URFs are the best circumstantial evidence for dual infection, which is defined as infection of the same individual with two or more genetically distinct strains. Studies have determined that dual infection is related to higher viral loads and faster CD4+ T-cell decline, and the acquisition of a superinfected drug-resistant strain could directly lead to the failure of antiretroviral therapy (ART) (Gottlieb et al, 2004; Cornelissen et al, 2012; Pingen et al, 2012). Only a few cases of triple HIV-1 infection have been reported (Takehisa et al, 1997; Gerhardt et al, 2005; van der Kuyl et al, 2005; Pernas et al, 2006; de Azevedo et al, 2019)

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