Transcriptionally Active Defective HIV-1 Proviruses and Their Association With Immunological Nonresponse to Antiretroviral Therapy
Francesca Scrimieri, Estella Bastian, Mindy Smith, Catherine Rehm, Caryn G. Morse, Janaki Kuruppu, Mary McLaughlin, Weizhong Chang, Irini Sereti, Joseph A. Kovacs, H. Clifford Lane, Hiromi Imamichi
Abstract
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.