Reviews and feature articles
HIV-1 superinfection

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Abstract

During the past year, a number of reports have described HIV-1 superinfection in human subjects, defined as the reinfection of an individual with a second heterologous strain of HIV-1. These reports have challenged the assumption that HIV-1–specific immune responses generated during primary infection are protective against subsequent infection and have raised concern, not only with respect to HIV-1–positive individuals engaging in unsafe sex but also from the standpoint of developing effective vaccines. Herein we review the published reports of HIV-1 superinfection and highlight studies providing additional insight into the potential for HIV-1 superinfections to affect the global epidemic.

Section snippets

AIDS virus superinfections in animal models

The potential for HIV-1 superinfection to occur was first described in chimpanzees,23 although the reality of this phenomenon occurring in human subjects remained speculative. Supporting in vitro evidence for HIV-1 superinfection was generated from studies documenting the ability to superinfect chronically HIV-1–infected T cells.23 In contrast, other in vitro studies indicated that reinfection might be prevented through various aspects, including CD4 downregulation and post entry interference.24

HIV-1 superinfection

Although the data from animal models show that superinfection is possible, until recently, no convincing case of HIV-1 superinfection in human subjects had been described. A number of studies, however, had reported HIV-1 coinfection with 2 genetically distinct HIV-1 strains belonging either to the same subtype (intrasubtype) or different subtypes (intersubtype).11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22 Because most of these coinfections were identified in cross-sectional studies, the

HIV-1 recombination

Aside from these few documented reports, perhaps the most compelling data that HIV-1 superinfections are occurring comes from the growing number of circulating recombinant forms of group M HIV-1 viruses being identified. Fig 2 illustrates the phylogenetic relationship (sequence heterogeneity) between group M (subtypes A-K), group O, and group N HIV-1 strains. Therefore recombinant forms of group M viruses stand to further increase the global sequence heterogeneity of HIV-1. To date, there are

Conclusions-implications for vaccine design

A number of recent reports indicate that HIV-1 superinfection can occur in infected individuals. These data are worrisome because they challenge the assumption that virus-specific immune responses induced by a primary infection are protecting against subsequent infection with a secondary HIV-1 strain. However, it is not possible at this time to determine the frequency by which HIV-1 superinfection occurs and to evaluate the factors that might influence the outcome of a second encounter with a

Acknowledgements

We thank Christian Brander and Bruce D. Walker for thoughtful and critical review of this manuscript.

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