Background:  Spontaneous 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.

Results:  This 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.