Dataset Information

Virological and immunological correlates of HIV post-treatment control after temporal antiretroviral therapy during acute HIV infection.

ABSTRACT:

Objective

People with HIV rarely control viral replication after cessation of antiretroviral therapy (ART). We present a person with HIV with extraordinary post-treatment control (PTC) for over 23 years after temporary ART during acute HIV infection (AHI) leading to a new insight in factors contributing to PTC.

Design/methods

Viral reservoir was determined by HIV qPCR, Intact Proviral DNA Assay and quantitative viral outgrowth assay. Viral replication kinetics were determined in autologous and donor PBMC. IgG levels directed against HIV envelope and neutralizing antibodies were measured. Immune phenotyping of T-cells and HIV-specific T-cell responses were analyzed by flow cytometry.

Results

The case presented with AHI and a plasma viral load of 2.7 million copies/mL. ART was initiated 2 weeks after diagnosis and interrupted after 26 months. Replicating virus was isolated shortly after start ART. At 18 years after treatment interruption HIV-DNA in CD4+ T-cells and low levels of HIV-RNA in plasma (<5 copies/ml) were detectable. Stable HIV envelope glycoprotein-directed IgG was present during follow-up, but lacked neutralizing activity. Strong antiviral CD8+ T-cell responses, in particular targeting HIV-gag, were detected during 25 years follow-up. Moreover, we found a P255A mutation in an HLA-B∗44:02 restricted gag-epitope, which was associated with decreased replication.

Conclusion

We describe an exceptional case of post-treatment control, which is likely associated with sustained potent gag-specific CD8+ T-cell responses in combination with a replication attenuating escape mutation in gag. Understanding the initiation and preservation of the HIV-specific T-cell responses could guide the development of strategies to induce HIV control.

SUBMITTER: van Paassen PM

PROVIDER: S-EPMC10653294 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Publications

Virological and immunological correlates of HIV posttreatment control after temporal antiretroviral therapy during acute HIV infection.

van Paassen Pien M PM van Pul Lisa L van der Straten Karlijn K Buchholtz Ninée V J E NVJE Grobben Marloes M van Nuenen Ad C AC van Dort Karel A KA Boeser-Nunnink Brigitte D BD van den Essenburg Mo D MD Burger Judith A JA van Luin Matthijs M Jurriaans Suzanne S Sanders Rogier W RW Swelsen Wendy T WT Symons Jori J Klouwens Michelle J MJ Nijhuis Monique M van Gils Marit J MJ Prins Jan M JM de Bree Godelieve J GJ Kootstra Neeltje A NA

AIDS (London, England) 20230911 15

<h4>Objective</h4>People with HIV rarely control viral replication after cessation of antiretroviral therapy (ART). We present a person with HIV with extraordinary posttreatment control (PTC) for over 23 years after temporary ART during acute HIV infection (AHI) leading to a new insight in factors contributing to PTC.<h4>Design/methods</h4>Viral reservoir was determined by HIV qPCR, Intact Proviral DNA Assay, and quantitative viral outgrowth assay. Viral replication kinetics were determined in a ...[more]

PMID: 37702421

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