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

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.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.HIV-1 superinfection presents an additional concern to the already challenging problem of HIV-1 vaccine design in the face of the virus's rapid evolution [1]. Superinfection is defined as a reinfection by a heterologous HIV-1 strain after a primary immune response has already been mounted [2]. Superinfection and coinfection (primary infection with two genetically distinct viruses) differ based on whether the second infection is contracted prior to or after the host immune response has been mounted [3]. The first documented case of superinfection was ide