A case report of HIV-1 superinfection in an HIV controller leading to loss of viremia control: a retrospective of 10 years of follow-up.

Background: HIV controllers (HICs) are a rare group of HIV-1-infected individuals able to naturally control viral replication. Several studies have identified the occurrence of HIV dual infections in seropositive individuals leading to disease progression. In HICs, however, dual infections with divergent outcomes in pathogenesis have been described.
Case Presentation: Here, we present a case report of a HIC diagnosed in late 1999 who displayed stable CD4 ⁺ T cell levels and low plasmatic viral load across 12 years of follow-up. In early 2013, the patient started to present an increase in viral load, reaching a peak of 10,000 copies/ml in early 2014, followed by an oscillation of viremia at moderate levels in the following years. The genetic diversity of env proviral quasispecies from peripheral blood mononuclear cells (PBMCs) was studied by single genome amplification (SGA) at six timepoints across 2009-2017. Phylogenetic analyses of env sequences from 2009 and 2010 samples showed the presence of a single subtype B variant (called B ₁ ). Analyses of sequences from 2011 and after revealed an additional subtype B variant (called B ₂ ) and a subsequent dominance shift in the proviral quasispecies frequencies, with the B ₂ variant becoming the most frequent from 2014 onwards. Latent syphilis related to unprotected sexual intercourse was diagnosed a year before the first detection of B _2, evidencing risk behavior and supporting the superinfection hypothesis. Immunologic analyses revealed an increase in CD8 ⁺ and CD4 ⁺ T cell immune activation following viremia increase and minor T cell subset alterations during follow-up. HIV-specific T cell responses remained low throughout the follow-up period.
Conclusions: Altogether, these results show that loss of viremia control in the HIC was associated with superinfection. These data alert to the negative consequences of reinfection on HIV pathogenesis, even in patients with a long history of viremia control and an absence of disease progression, reinforcing the need for continued use of adequate prevention strategies.