Lack of persistent drug-resistant mutations evaluated within and between treatment interruptions in chronically HIV-1-infected patients

Abstract

To determine the effect of treatment interruptions (TI) on the evolution and persistence of drug-resistant viruses in chronically HIV-1-infected suppressed patients. The emergence of viral resistance to combination antiretroviral therapy was monitored in 11 suppressed chronically HIV-1-infected patients undergoing from one up to four sequential TI (a total of 25 TI), by genotyping of the virus for known mutations in the genes for protease and reverse transcriptase. Resistance assays were performed at the first viral rebound > 100 copies/ml. All subjects achieved resuppression of HIV-1 under the same antiretroviral therapy, regardless of the number of TI. Five of eleven patients showed no development of resistance. In the remaining six patients, the following patterns of mutations associated with viral resistance were found: one mutation (K70R), which was observed in one patient during the 1st TI and persisted during follow-up; two mutations (L90M, M184V), which were observed in four patients during the 1st TI and were intermittently present or lost following extended TI, treatment reinitiation and/or during subsequent TI; and evolution of two mutations (M184V, K219E) observed in two patients. These two mutations were not present during the 1st TI and were subsequently lost following therapy reinitiation or during the next TI. Detection of drug resistance during TI by virus genotyping assays does not predict failure to resuppress after antiretroviral therapy reinitiation nor persistence of a resistant viral population during extended interruptions or subsequent TI.