Trends in drug resistance-associated mutations in a real-life cohort of Italian patients infected with HIV-1.

Abstract

Recent studies support the idea that human immunodeficiency virus type 1 (HIV-1) drug resistance is declining in developed countries. To help assess the current situation in Italy, the dynamics of drug resistance mutations in pol and integrase genes in plasma samples from HIV-1-positive patients attending Sapienza University Hospital, Rome, from 2003 to 2014 were analysed. In total, 1730 genotype resistance tests (GRTs) were retrospectively analysed. The prevalence of major drug resistance mutations (DRMs) was evaluated over time in the global population and in patients with antiretroviral therapy (ART) failure. Population dynamics, changes in ART administration, and HIV-1 RNA levels were analysed in combination with DRM trends. The global population showed a strong reduction in major DRMs to all drug classes. Over the 2003-2014 decade, resistance to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) declined from 80.0% to 18.7%, from 42.8% to 20.1% and from 74.2% to 8.3%, respectively (P<0.005 for all comparisons). However, only PI-associated mutations showed a significant decrease in patients experiencing ART failure. Interestingly, analysis of the integrase gene disclosed an increased resistance to integrase inhibitors, mainly regarding N155H, detected in 32.6% of raltegravir-treated patients in 2012-2014. In conclusion, in line with previous findings, this study shows that drug resistance is declining in Italy. However, the persistence of DRMs to NRTIs and NNRTIs suggests that despite adherence and treatment optimisation, some patients still experience therapy failure, emphasising the need for GRTs both in naïve and ART-failed patients.