Immunological and virological results in a patient with exceptional post-therapeutic control: about a case

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Background

Although antiretroviral therapy (ART) is effective in suppressing viral replication, HIV-1 persists in reservoirs and rebounds after stopping ART. However, very few people (eg, elite and post-treatment controllers) are able to maintain viral loads below detection limits without ART, constituting a realistic model of long-term HIV remission. Here, we describe the HIV control mechanisms of an individual who showed exceptional post-treatment control for over 15 years.

Methods

We report the case of a 59-year-old Hispanic woman with acute sexually acquired HIV infection, who was enrolled in an immune-mediated HIV primary infection trial involving short course ciclosporin A, interleukin-2, granulocyte-macrophage colony-stimulating factor, and pegylated interferon alfa, followed by analytical discontinuation of treatment. We performed the following viral assays: total and integrated HIV-1 DNA in CD4 T cells and rectal tissue, quantitative viral outgrowth assay, HIV-1 infectivity in peripheral blood mononuclear cells and lymphocyte cultures CD4 T cells and inhibitory viral activity by natural killer (NK) and CD8 T cells. NK and T cell phenotypes were determined by flow cytometry. HLA, killer cell immunoglobulin-like receptors, Δ32CCR5and NKG2C the alleles were genotyped.

Results

After ART and immunomodulatory treatment, the person maintained an undetectable plasma viral load for 15 years. The HIV-1 subtype was CFR_02AG, CCR5-tropic. We found progressive reductions in the viral reservoir during the 15-year treatment interruption: total HIV DNA (from 4,573,50 copies for 10 years6 CD4 T cells at 95 33 copies per 106 CD4 T cells) and integrated DNA (from 85 37 copies for 106 CD4 T cells at 5 25 copies per 106 CD4 T cells). Viral inhibition assays showed strong inhibition of HIV replication in vitro in co-cultures of CD4 T cells with autologous NK or CD8 T cells at a ratio of 1:2 (75% and 62%, respectively ). Co-cultures with NK and CD8 T cells resulted in 93% inhibition. We detected above baseline levels of NKG2C memory-like NK cells (46·2%) and NKG2C γδ T cells (64·9%) associated with HIV-1 control.

Interpretation

We described long-term remission in a 59-year-old woman who was treated for primary HIV infection and maintained an undetectable viral load for 15 years without ART. Replication competent HIV-1 has been isolated. NKG2C memory-like NK cells and γδ T cells were associated with control viral replication. Strategies favoring these cells could lead to long-term HIV remission.

Funding

Fondo Europeo para el Desarrollo Regional (FEDER), SPANISH AIDS Research Network (RIS), Fondo de Investigación Sanitaria (FIS), HIVACAT, Institute for Biomedical Investigations August Pi i Sunyer (IDIBAPS), Program CERCA/Generalitat de Catalunya, la Caixa Foundation, and Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC).

Translation

For the Spanish translation of the summary, see the Additional Documents section.

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