Timing and source of subtype-C HIV-1 superinfection in the newly infected partner of Zambian couples with disparate viruses

Abstract

BackgroundHIV-1 superinfection occurs at varying frequencies in different at risk populations. Though seroincidence is decreased, in the negative partner of HIV-discordant couples after joint testing and counseling in the Zambia Emory HIV Research Project (ZEHRP) cohort, the annual infection rate remains relatively high at 7-8%. Based on sequencing within the gp41 region of each partner's virus, 24% of new infections between 2004 and 2008 were the result of transmission from a non-spousal partner. Since these seroconvertors and their spouses have disparate epidemiologically-unlinked viruses, there is a risk of superinfection within the marriage. We have, therefore, investigated the incidence and viral origin of superinfection in these couples.ResultsSuperinfection was detected by heteroduplex mobility assay (HMA), degenerate base counting of the gp41 sequence, or by phylogenetic analysis of the longitudinal sequences. It was confirmed by full-length env single genome amplification and phylogenetic analysis. In 22 couples (44 individuals), followed for up to five years, three of the newly infected (initially HIV uninfected) partners became superinfected. In each case superinfection occurred during the first 12 months following initial infection of the negative partner, and in each case the superinfecting virus was derived from a non-spousal partner. In addition, one probable case of intra-couple HIV-1 superinfection was observed in a chronically infected partner at the time of his seroconverting spouse's initial viremia. Extensive recombination within the env gene was observed following superinfection.ConclusionsIn this subtype-C discordant couple cohort, superinfection, during the first year after HIV-1 infection of the previously negative partner, occurred at a rate similar to primary infection (13.6% [95% CI 5.2-34.8] vs 7.8% [7.1-8.6]). While limited intra-couple superinfection may in part reflect continued condom usage within couples, this and our lack of detecting newly superinfected individuals after one year of primary infection raise the possibility that immunological resistance to intra-subtype superinfection may develop over time in subtype C infected individuals.

Evaluation of postpartum HIV superinfection and mother-to-child transmission

“…It is unknown what role HIV SI has on MTCT or sexual transmission, but given the effect it has on viral load, it is possible that SI could temporarily increase the infectiousness of the individual. However, it is difficult to establish the directionality and relationship of SI and transmission events in the setting of sexual transmission [4, 7]. This issue is not relevant in MTCT of HIV, since transmission only occurs vertically.…”

“…HIV SI has been demonstrated in multiple cohorts around the world, and occurs at varying rates that can be similar to the corresponding primary HIV incidence rate in the population, although this has not been observed in all studies [2-7]. Rates of HIV SI appear to be higher in populations at increased risk of primary HIV infection, such as female sex-workers [8].…”

“…HIV SI can cause temporary and sustained increases in viral load, which could increase the risk of HIV transmission to other individuals [4, 9, 10]. Examining the role of SI and sexual transmission in HIV discordant sexual partnerships is difficult since it is often impossible to establish if the SI event occurred prior to the subsequent transmission, or vice versa [7]. In contrast, studying SI in the context of MTCT of HIV through breastfeeding is simpler, because there is no question about the directionality of SI and subsequent transmission, and because there are fewer confounding behavioral factors.…”

Immunological and virological characteristics of human immunodeficiency virus type 1 superinfection: implications in vaccine design

“…A hypothesis is that superinfection occurs more easily at the early infection stage because of weak immunity. This hypothesis was initially supported by some case reports and cohort studies showing superinfection within one year after initial infection [4,7,12,22,28,39,42,64]. However, later studies showed that the number of superinfection within one year after the initial infection was similar to that after one year of infection [11,19,41,51,74].…”

Molecular tools for studying HIV transmission in sexual networks

“…When individuals are infected with multiple viruses either at the time of initial infection or later, a bulk sequence will not adequately represent all viruses that an individual has acquired or possibly transmitted[31,32]. In these instances SGA and NGS methods can provide a more detailed depiction of intra-host HIV diversity[33-35]. Phylogenies reconstructed from bulk sequences may be subject to greater bias with increasing prevalence of HIV coinfection within a population, though this remains an understudied area in phylogenetics.…”