Intersubtype Human Immunodeficiency Virus Type 1 Superinfection following Seroconversion to Primary Infection in Two Injection Drug Users

Abstract

In this study, we describe two cases of human immunodeficiency virus type 1 (HIV-1) intersubtype superinfection with CRF01_AE and subtype B strains, which occurred in two injection drug users participating in a prospective cohort study in Bangkok, Thailand. In both cases, the superinfecting strain was detected by molecular and serologic analyses several weeks after complete seroconversion to the primary infection with a strain belonging to a different subtype. Superinfection occurred despite specific T-cell and humoral antibody responses to the primary virus. In both cases, cross-subtype immune responses were limited or absent prior to the second infection. These data show that, in some individuals, the quality and quantity of the immune response elicited by primary HIV-1 infection may not protect against superinfection. This finding has important implications for vaccine design. HIV-1 vaccines, at a minimum, will need to include potent, broadly protective, conserved immunogens derived from several group M subtypes.

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“…Therefore, it is likely that the susceptibility to superinfection is higher during the first year following primary infection, when HIV-1-specific humoral immunity is not fully developed, and the discrepancies between the abovementioned studies might be explained by differences in the time elapsed between the initial and the second infection. This hypothesis is supported by initial observations in HIV-2-infected macaques, which can only become productively superinfected by a distinct HIV-2 virus within 8 weeks following primary infection [22], and by a substantial percentage of documented superinfections that occurred within one year of primary HIV-1 infection in humans [11,30,31,33,34].…”

“…While the neutralizing antibody response was found to be low, a cellular response of this magnitude and breath did not translate into protection against the second HIV-1 strain even though its sequence only differed by 12%. Thus, these and additional well-documented cases demonstrated that superinfection can occur in the context of limited HIV-1-specific cytotoxic T cell responses mostly directed against a single epitope [10,35], yet it is not prevented by the presence of broad responses to multiple epitopes [9,11,34,39].…”

“…The first convincing report of HIV-1 superinfection described two events in injection drug users (IDUs), with the second HIV-1 strain belonging to a different subtype in both situations [11]. Co-rather than superinfection could not be entirely excluded, yet humoral and cellular immune responses were exclusively directed against one HIV-1 strain prior to potential exposure to the second virus, strongly suggesting superinfection, with cross-reactive humoral and cellular responses developing after presumed infection with the second strain.…”

“…At a time when HIV-1 dual infections had not been adequately documented, the existence of recombinant forms provided the strongest support for their occurrence, which represents an important mechanism to generate new divergent HIV-1 strains. For instance, at the time HIV-1 superinfection was first reported in humans in 2002 [9][10][11], 14 circulating recombinant forms (CRFs) had been described. Today, the Los Alamos database reports 58 HIV-1 CRFs and 1 HIV-2 CRF, and as more HIV-1 variants inevitably intermix in different parts of the world, the likelihood of generating new recombinant viruses increases [6].…”

“…Since then, multiple reported cases have described interclade [10,11,[23][24][25][26][27][28][29] as well as intraclade [9,[30][31][32][33][34][35] superinfections, but also triple superinfections [28,32,36], or superinfections involving substantially divergent strains belonging to the different HIV-1 and HIV-2 groups [37,38].…”