What Is the most Important for Elite Control: Genetic Background of Patient, Genetic Background of Partner, both or neither? Description of Complete Natural History within a Couple of MSM

Abstract

Background

We describe a homosexual man who strongly controlled HIV-1 for ten years despite lack of protective genetic background.

Methods

HIV-1 DNA was measured in blood and other tissues. Cell susceptibility was evaluated with various strains. HIV-1-specific (CD4 and CD8 activation markers and immune check points) and NK cells responses were assessed; KIRs haplotypes and HLA alleles were determined.

Findings

Two HIV-1 RNA copies/mL of plasma were detected in 2009, using an ultra-sensitive assay. HIV-DNA was detected at 1.1 and 2 copies/10 ⁶ PBMCs in 2009 and 2015 respectively, at 1.2 copies/10 ⁶ cells in rectal cells in 2011. WBs showed weak reactivity with antibodies to gp160, p55 and p25 from 2007 to 2014, remaining incomplete in 2017. CD4 T cells were susceptible to various strains including HIV _KON, a primary isolate of his own CRF02_AG variant. CD8 T cells showed a strong poly-functional response against HIV-Gag, producing mainly IFN-γ; a robust capacity of antibody-dependant cell cytotoxicity (ADCC) was observed in NK cells. Case patient was group B KIR haplotype. Neutralizing antibodies were not detected. CD4 and CD8 blood T cells showed normal proportions without increased activation markers. Phylogenetic analyses identified the same CRF02_AG variant in his partner. The patient and his partner were heterozygous for the CCR5ΔD32 deletion and shared HLA-B*07, C*07 non-protective alleles.

Interpretation

This thorough description of the natural history of an individual controlling HIV-1 in various compartments for ten years despite lack of protective alleles, and of his partner, may have implications for strategies to cure HIV-1 infection.

Highlights

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  We described a MSM, elite controller despite pejorative genetic background.

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  The patient had two HLA pejoratives alleles and no protective alleles.

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  The partner was infected by the same strain.

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  The genetic backgrounds of the patient and partner, and the virus could interact with each other to lead to elite control.

We considered all the evidence about elite control, HLA, ADCC and NK, using Medline/PubMed. We described a MSM, elite controller despite non-protective genetic background, explored extensively the patient: sequential WBs, RNA in plasma (ultrasensitive assay), DNA in PBMC/GALT, cell susceptibility, HIV-1 responses in PBMC/LNMC, neutralizing antibodies, CD3-CD56 + NK, ADCC, KIRs. He had one HLA pejorative and no protective alleles. The partner was infected by the same strain, his genetic background was studied. The genetic background of the exposed person, of the source, and the viral strain could interact with each other to lead to elite control.