Clinical, virologic, and immunologic correlates of HIV-1 intraclade B dual infection among men who have sex with men

Abstract

Objective To investigate the susceptibilities to and consequences of HIV-1 dual infection (DI). Design We compared clinical, virologic, and immunologic factors between participants who were dually infected with HIV-1 subtype B, and monoinfected (MI) controls who were matched by ongoing HIV risk factor. Methods The viral load and CD4 progressions of dually and singly infected participant groups were compared with linear mixed-effects models, and individual dynamics before and after superinfection were assessed with a structural change test (Chow test). Recombination breakpoint analysis (GARD), HLA frequency analysis, and cytotoxic T-lymphocyte (CTL) epitope mapping were also performed (HIV LANL Database). Results The viral loads of DI participants increased more over 3 years of follow-up than the viral loads of MI controls, while CD4 progressions of the two groups did not differ. Viral escape from CTL responses following superinfection was observed in two participants whose superinfecting strain completely replaced the initial strain. This pattern was not seen among participants whose superinfecting virus persisted in a recombinant form with the initial virus or was only detected transiently. Several HLA types were overrepresented in DI participants as compared to MI controls. Conclusions These results identify potential factors for DI susceptibility and further define its clinical consequences.

Recombination-mediated escape from primary CD8+ T cells in acute HIV-1 infection

“…They add to, but are distinct from, two previous reports that describe superinfection in the chronic stage of HIV-1 infection. Those studies described the selection of the superinfecting strain because it contained mutations that conferred escape from circulating T cell responses [29,34]. In one of these studies, recombination was detected in a patient two months after the superinfection event, and was associated with T cell pressure [29].…”

Dynamics of Viral Evolution and Neutralizing Antibody Response after HIV-1 Superinfection

“…HIV RNA was extracted from blood plasma (QIAmp viral RNA mini kit; Qiagen, Hilden, Germany), and cDNA was generated (RETROscript kit; Applied Biosystems/ Ambion, Austin, TX) from extracted HIV-1 RNA for three or more time points over a minimum of 11 months. Single-genome sequencing (SGS) and UDS of PCR-amplified env C2-V3 (HXB2 coordinates 6928 to 7344), pol reverse transcriptase (RT; HXB2 coordinates 2708 to 3242), and gag p24 (HXB2 coordinates 1366 to 1619) were performed as described previously (4,11,20). All UDS and SGS sequences were screened for in-house cross-contamination using BLAST as previously described (21).…”

“…This process allows viral recombination to occur between distantly related strains and may facilitate immune evasion (1,2), development of drug resistance (3), and disease progression (4)(5)(6). Moreover, new circulating recombinant forms complicate vaccine development by expanding global viral diversity (7,8).…”

“…However, detection of superinfection is difficult and hinges on timing of sampling and molecular evidence of a genetically distinct viral subpopulation. The recent development of more sensitive next-generation sequencing techniques (e.g., ultradeep sequencing [UDS]) facilitates the identification of cases (4,11,12) and permits the assessment of intrahost viral subpopulation dynamics.…”

Risk Behaviors Among HIV-Positive Gay and Bisexual Men at Party-Oriented Vacations

“…Although researchers estimate that superinfections are present in less than 4% of sexually active MSM (Sidat et al, 2008) and that risk of superinfection is low (Cheonis, 2006;Diaz et al, 2005), superinfections-as well as co-infections (i.e., infection with two HIV strains at once)-have been found to be associated with lower CD4 cell counts (Cornelissen et al, 2012;Gottlieb et al, 2004;Smith et al, 2004) and greater increases of HIV viral load (Pacold et al, 2012;Smith et al, 2004). Because the likelihood of HIV-positive MSM engaging in risky seroconcordant or sero-unknown sex appears to increase with drug use (Purcell et al, 2005), superinfection may be a particular concern in settings where substance use is high.…”