Transcriptionally Active Defective HIV-1 Proviruses and Their Association With Immunological Nonresponse to Antiretroviral Therapy

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/mu L) and 25 immunological responders (IRs; CD4 >= 250 cells/mu L), 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.