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

Abstract

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.

Immunoescape of HIV-1 in Env-EL9 CD8 + T cell response restricted by HLA-B*14:02 in a Non progressor who lost twenty-seven years of HIV-1 control

“…Our results demonstrate the association between the presence of Env-EL9 immunodominant HLA-B*14:02-restricted CD8 + T-cell responses, viral evolution and immune escape with LVC. In contrast to other studies [ 29 – 31 ], the infection with two heterologous HIV-1 strains was not associated with LVC [ 20 , 24 , 32 ]. Our phylogenetic inferences describe viral evolution [ 5 ] and the potential contribution of variant emergence and replacement to LVC.…”

A Systematic Molecular Epidemiology Screen Reveals Numerous Human Immunodeficiency Virus (HIV) Type 1 Superinfections in the Swiss HIV Cohort Study

“…Other studies retrospectively analysed cases identified through patients' abnormal laboratory values (e.g. increased VL, decreased CD4 counts, changed resistance patterns) [8,9,20], or using proviral DNA [21,34,35], which was not yet used to screen for superinfection. Also, available tools to investigate dual infections [30] are not yet tailored to identify superinfection, nor to work with individuals' longitudinal sequences.…”

Viral and Cellular Factors Leading to the Loss of CD4 Homeostasis in HIV-1 Viremic Nonprogressors

“…The phenomenon of loss of control has been reported in studies of natural HIV-1 controllers, including elite controllers (ECs) and long-term nonprogressors (LTNPs) ( 10 , 11 , 37 – 40 ) aiming to delineate the biological correlates of spontaneous HIV-1 control. Nonetheless, it is currently unknown whether viremic nonprogressors (VNPs), a very rare phenotype characterized by a paradoxically nonpathogenic HIV-1 infection and sustained CD4 + T-cells counts despite continuous viral load, may eventually lose CD4 + homeostasis (LoH).…”