Rapid selection of drug-resistant HIV-1 during the first months of suppressive ART in treatment-naive patients

Abstract

Efficient antiretroviral therapy (ART) of HIV-1 infection reduces the viral load to undetectable levels and restores the immune system. However, therapy failure appears in a substantial fraction of patients and is mostly associated with the appearance of drug-resistant viruses. It is still not clear when the drug pressure leads to the earliest selection and appearance of drug-resistant HIV-1 populations. In this study, we wanted to determine whether drug-resistant viruses are already selected during viral decline within the first months of ART. Fifteen mostly chronically HIV-1 infected patients were included. None had received ART prior to this study. The selection of three key resistance mutations, L90M (protease), K103N and M184V (reverse transcriptase), were measured by allele-specific real-time PCR allowing us to track minority quasispecies with a discriminative power of 0.01-0.2%. Drug-resistant HIV-1 variants were found in 7/15 patients (46.7%) prior to ART. Rapid selection of drug resistance was detected in six patients (40%) independent of the presence of drug-resistant HIV-1 prior to ART. The risk for the selection of drug resistant viruses was correlated with the time until viral load became undetectable (P = 0.02). Besides the proportional increment of drug-resistant viruses, we observed in two patients a quantitative increase of this virus population while the total viral load decreased. Drug-resistant viruses can be selected and replicate even in the first weeks of suppressive ART, thus, intensification of ART during the initial treatment period should be considered and further evaluated in clinical studies.