Detection of residual human immunodeficiency virus type 1 reverse transcriptase K103N minority species in plasma RNA and peripheral blood mononuclear cell DNA following discontinuation of non-nucleoside therapy

Abstract

Non-nucleoside reverse transcriptase inhibitor (NNRTI) therapy failed in 30 patients with the typical human immunodeficiency virus type 1 reverse transcriptase K103N mutation, detected using standard genotyping. Following discontinuation of NNRTI therapy for a median of 55.9 weeks and a decrease of K103N mutant species to undetectable levels in plasma RNA, minority K103N species remained detectable, by allele-specific PCR, for longer periods of time and at higher frequency, in peripheral blood mononuclear cell (PBMC) DNA than in plasma RNA (76.7% and 46.7% of samples with residual K103N species detected at median frequencies of 18.0% and 3.8%, respectively). Analysis of PBMC DNA should be considered when searching for residual K103N mutant species in patients previously exposed to NNRTIs.

Minor drug-resistant human immunodeficiency virus (HIV)-1 variants in the cellular DNA of Tanzanian women following triple antiretroviral regimen to prevent vertical transmission

“…These women had taken antenatal AZT for 40, 91 and 105 days (Table 1), potentially allowing the selection and integration of AZT resistance mutations. The K103N mutation (detected in PBMCs only of one woman) has been reported to be detectable for longer periods and at higher frequencies in PBMC HIV than in plasma RNA (Saladini et al, 2010).…”

“…Such discrepancies in the occurrence and persistence of drug resistance mutations between plasma RNA and PBMC DNA have been reported in several studies, demonstrating that the PBMC compartment does not necessarily reflect the plasma compartment (Saladini et al, 2010;Turriziani et al, 2010;Wind-Rotolo et al, 2009). While plasma samples provide information on actively replicating viruses (Turriziani et al, 2010), cellular HIV-DNA reflects both actively and latently infected cells (Wirden et al, 2011).…”

The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy

“…Besides the replication fitness, K103N can persist for a long time in naive patients, over 2 years in a present case report [ 36 ]. K103N also can be found in blood mononuclear cell (PBMC) DNA, with no K103N observed in plasma [ 37 , 38 ]. All the previous research indicated that K103N can steadily exist in plasma and PBMC, and quasispecies with K103N could be more possibly to survive in the surrounding with NVP.…”