Viral Divergence in 2 Groups of Partnerships: Superinfection or Sequential Expression of Dual Infection?
Jeff McConnell*1, L Bragg1, T Schmidt2, T Liegler3, and R Grant1
1Gladstone Inst of Virology and Immunology, San Francisco, CA, US; 2AIDS Res Inst, Univ of California, San Francisco, US; and 3Univ of California, San Francisco, US
Background: Reports of HIV-1 super-infection have
mostly involved recent seroconverters, in whom the incidence of apparent
superinfection is comparable to the incidence of primary HIV infection. In
contrast, super-infection among chronically infected persons is rare. The
prevalence of primary and co-infection in North America is not known.
Methods: The Positive Partners study in San Francisco was a prospective cohort of 435 HIV+ individuals who enrolled
with a seroconcordant sexual partner (partner Group A) or reported unprotected
intercourse with multiple unenrolled seropositive partners (partner Group B).
Eligibility was based on reported unprotected intercourse (UI) with HIV+
partners in the past year. Pol, gag, and tat population
sequences were analyzed phylogenetically; among individuals suppressed on ART
sequences were derived from proviral DNA.
Results: In Group A, 242 persons involving 178
partnerships were followed, 86% of the cohort reported more than 2 years since
HIV diagnosis (median = 9.7 years). A total of 229.5 person-years of
observation occurred and 16,987 episodes of UI were reported. An additional 48 persons
contribute to 836 Group B partnerships and 3294 episodes of UI. Despite this
high level of exposure no super-infection in Group A linked to a virologically
characterized enrollment partner was detected. Apparent dual infections,
indicated by phylogenetically divergent virus populations at separate
timepoints, were observed in 10 individuals primarily in DNA (9 of 175) of
virologically suppressed participants and 1 in RNA (1 of 115).
Conclusions: The lack of systemic super-infection in
partnerships with known exposure to divergent viruses (Group A, 0 of 230
person-years) and only 1 systemic SEDI not acquired from an enrolled partner in
a monogamous individual (Cohort B, 0 of 836 UAI partnerships) was less than
expected in the absence of mechanisms blocking HIV super-infection. Given high
rates of primary co-infection reported in subtype B epidemics (24%, US)
evidence of divergent viral strains, especially in DNA during suppressive
therapy may reflect frequent primary co-infection. Intensive virological
assessment of recently infected individuals for evidence of primary co-infection
and follow-up to document sequential expression of co-infecting viral variants would
clarify inquiry into whether appearance of divergent viral variants reflects
HIV-1 super-infection or SEDI of initially co-infected persons.