Regain of Viremic Control after Superinfection of an Elite Controller of HIV-1 Infection
Andrea Rachinger*1, M Navis1, P Groeneveld2, A Van't Wout1, and H Schuitemaker1
1Sanquin Res and Academic Med Ctr, Univ of Amsterdam, The Netherlands and 2Isala Clin, Zwolle, The Netherlands
and sustained control of HIV infection to <50 copies of viral RNA/mL plasma
in the absence of therapy is rare and represents a distinct phenotype among
HIV-infected individuals (elite controllers). It is unknown how this viremic
control is established and whether it is determined by host factors, viral
factors, or a combination of both.
Methods: We performed
a longitudinal analysis of immunological parameters and viral RNA load in
plasma in an elite controller of who experienced a transient viremia. We performed
phylogenetic analysis on gag, pol, and env sequences from his HIV-1 variants
(either replication-competent virus isolated from peripheral blood mononuclear
cells [PBMC] or viral RNA from plasma) and from virus variants isolated from
PBMC or plasma from his HIV-infected partner.
elite controller had an undetectable viral load (<25 copies HIV-1 RNA/mL plasma)
for at least 13 years and was viremic for the first time in December 2004 (95
copies HIV-1 RNA/mL plasma). Viral load then decreased to below the detection
limit of the assay (<25 copies HIV-1 RNA/mL plasma), subsequently increased
to 2300 copies HIV-1 RNA/mL plasma in November 2005, reaching a maximum of 25,000
copies HIV-1 RNA/mL plasma in April 2006 before it declined again to below the
detection limit of the assay. Interestingly, a viral gag sequence obtained from
the elite controller in December 2004 was phylogenetically distinct from the
HIV-1 gag sequences obtained at later time points. Furthermore, viral gag and env
sequences from the later time-points clustered with sequences from his current HIV-1-infected
partner with whom he engaged in unprotected sexual contact after March 2005. Detailed
phylogenetic analysis was consistent with superinfection of this elite
controller by his partner.
Conclusions: The regain
of natural elite control after superinfection with a replication-competent unrelated
virus variant in this individual clearly argues for host factors as a major
component in protection against HIV-1 disease progression.