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

Abstract

e Investigating the incidence and prevalence of HIV-1 superinfection is challenging due to the complex dynamics of two infecting strains. The superinfecting strain can replace the initial strain, be transiently expressed, or persist along with the initial strain in distinct or in recombined forms. Various selective pressures influence these alternative scenarios in different HIV-1 coding regions. We hypothesized that the potency of the neutralizing antibody (NAb) response to autologous viruses would modulate viral dynamics in env following superinfection in a limited set of superinfection cases. HIV-1 env pyrosequencing data were generated from blood plasma collected from 7 individuals with evidence of superinfection. Viral variants within each patient were screened for recombination, and viral dynamics were evaluated using nucleotide diversity. NAb responses to autologous viruses were evaluated before and after superinfection. In 4 individuals, the superinfecting strain replaced the original strain. In 2 individuals, both initial and superinfecting strains continued to cocirculate. In the final individual, the surviving lineage was the product of interstrain recombination. NAb responses to autologous viruses that were detected within the first 2 years of HIV-1 infection were weak or absent for 6 of the 7 recently infected individuals at the time of and shortly following superinfection. These 6 individuals had detectable on-going viral replication of distinct superinfecting virus in the env coding region. In the remaining case, there was an early and strong autologous NAb response, which was associated with extensive recombination in env between initial and superinfecting strains. This extensive recombination made superinfection more difficult to identify and may explain why the detection of superinfection has typically been associated with low autologous NAb titers.

Increased HIV-1 superinfection risk in carriers of specific human leukocyte antigen alleles

“…During the follow-up time, 10 individuals became superinfected with HIV-1 within 2 years after primary infection, which is in agreement with previous studies demonstrating that most superinfections occur within the first 2 years of incident infection [5,8]. One of these superinfected individuals (the first superinfected individual in Table 3) has previously been shown to display evidence for a recombination event between original and superinfected viral populations [34]. The univariate results of our study suggest that a higher number of sexual contacts (more than three contacts per month) and specific HLA alleles may play an important role in the risk of HIV-1 superinfection, whereas race/ethnicity, age, higher frequency of condomless anal intercourse, lower CD4 + T-cell count and higher viral load are not significantly associated with increased superinfection risk in this high-risk cohort of MSM.…”

Low antibody-dependent cellular cytotoxicity responses in Zambians prior to HIV-1 intrasubtype C superinfection

“…These data taken together suggested that potentially protective IgG neutralizing and binding antibodies were lower prior to re-infection in the superinfected group compared to similar time points for the non-superinfected group, representing potential correlates of HIV-1 protection. These data are also consistent with superinfection studies in intrasubtype B superinfected men having sex with men that have shown lower levels of neutralizing antibodies prior to superinfection (4, 5). However, a reduced antibody response was not observed in studies of multi-clade superinfected Kenyan female sex workers (6); although, in this same cohort, a significantly decreased risk of superinfection after the first year of primary infection was consistent with the development of resistance to re-infection (7).…”

Intrasubtype B HIV-1 Superinfection Correlates with Delayed Neutralizing Antibody Response

“…One participant in this study developed substantial NAb breadth and potency after becoming superinfected. Interestingly, this participant's env sequences were the only ones that had evidence of recombination between initial and superinfecting viruses, as we reported previously (19). Three previous studies (8,20,21) reported that superinfected individuals develop broad and potent NAb (bNAb) responses, with some of them becoming elite neutralizers.…”