Transcriptionally-active "defective" HIV-1 proviruses and their association with immunological non-response to antiretroviral therapy

Author:

Scrimieri, Francesca

Bastian, Estella

Smith, Mindy

Rehm, Catherine A

Morse, Caryn

Kuruppu, Janaki

McLaughlin, Mary

Chang,Weizhong [ORCID]

Sereti, Irini

Kovacs, Joseph A

Lane, H Clifford

Imamichi, Hiromi [ORCID]
Author Address

Frederick National Laboratory for Cancer Research, Frederick, Maryland, U.S.A., National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, U.S.A., Critical Care Medicine Department, NIH Clinical Center, Bethesda, Maryland, U.S.A.,

Abstract:

A subset of antiretroviral therapy-treated persons with HIV, referred to as immunological non-responders (INRs), fails to normalize CD4+ T-cell numbers. In a case-control study involving 26 INRs (CD4< 250 cells/µL) and 25 immunological responders (IRs, CD4=250 cells/µL), we evaluated the potential contribution of transcriptionally-competent "defective" HIV-1 proviruses to poor CD4+ T-cell recovery. Compared to the responders, the INRs had higher levels of cell-associated HIV-RNA (p=0.034) and higher percentages of HLA-DR+CD4+ T-cells (p< 0.001). While not encoding replication-competent viruses, the RNA transcripts frequently encoded HIV-1 Gag-p17 and Nef proteins. These transcripts and/or resulting proteins may activate pathway(s) leading to the immunological non-response phenotype. Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.

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Author Address