Transcriptionally Active Defective HIV-1 Proviruses and Their Association With Immunological Nonresponse to Antiretroviral Therapy.
Francesca ScrimieriEstella BastianMindy SmithCatherine A RehmCaryn MorseJanaki KuruppuMary McLaughlinWeizhong ChangIrini SeretiJoseph A KovacsH Clifford LaneHiromi ImamichiPublished in: The Journal of infectious diseases (2024)
A subset of antiretroviral therapy-treated persons with human immunodeficiency virus (HIV), referred to as immunological nonresponders (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 = .034) and higher percentages of HLA-DR+ CD4+ T cells (P < .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 nonresponse phenotype.
Keyphrases
- antiretroviral therapy
- human immunodeficiency virus
- hiv infected
- hiv positive
- hiv aids
- hiv infected patients
- hepatitis c virus
- induced apoptosis
- hiv testing
- men who have sex with men
- stem cells
- cell cycle arrest
- signaling pathway
- single cell
- south africa
- climate change
- endoplasmic reticulum stress
- cell therapy
- nk cells