title: Timing and source of subtype-C HIV-1 superinfection in the newly infected partner of Zambian couples with disparate viruses.
abstract: BACKGROUND
  HIV-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.
  
  
  RESULTS
  Superinfection 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.
  
  
  CONCLUSIONS
  In 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.
authors.affiliation: Emory Vaccine Center at Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
authors.forename: Colleen S
authors.initials: CS
authors.lastname: Kraft
authors.forename: Debby
authors.initials: D
authors.lastname: Basu
authors.forename: Paulina A
authors.initials: PA
authors.lastname: Hawkins
authors.forename: Peter T
authors.initials: PT
authors.lastname: Hraber
authors.forename: Elwyn
authors.initials: E
authors.lastname: Chomba
authors.forename: Joseph
authors.initials: J
authors.lastname: Mulenga
authors.forename: William
authors.initials: W
authors.lastname: Kilembe
authors.forename: Naw H
authors.initials: NH
authors.lastname: Khu
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Derdeyn
authors.forename: Susan A
authors.initials: SA
authors.lastname: Allen
authors.forename: Olivier
authors.initials: O
authors.lastname: Manigart
authors.forename: Eric
authors.initials: E
authors.lastname: Hunter
mesh_terms: D000328:Adult; D060085:Coinfection / Q000453:epidemiology* / Q000821:virology; D005191:Family Characteristics; D005838:Genotype; D015700:HIV Envelope Protein gp41 / Q000235:genetics; D015658:HIV Infections / Q000453:epidemiology* / Q000821:virology; D015497:HIV-1 / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D015994:Incidence; D008297:Male; D017720:Molecular Epidemiology; D008969:Molecular Sequence Data; D017422:Sequence Analysis, DNA; D013997:Time Factors; D015024:Zambia
chemical_list: D015700:HIV Envelope Protein gp41; C514787:gp41 protein, Human immunodeficiency virus 1