Prevalence and factors associated with HIV-1 multidrug resistance over the past two decades in the Italian Arca database

Despite successful antiretroviral therapy, HIV-infected people could develop multi-class drug resistance (MDR). Here we aimed to explore the prevalence of HIV-1 drug resistance over the past two decades by focusing on HIV-MDR and its predictors. This is a retrospective study of ART-experienced HIV-infected patients with at least one plasma genotypic resistance test (GRT) available, collected from 1998 to 2018 from the ARCA database. Temporal trend of resistance to any drug class was evaluated by considering all GRTs. Prevalence and predictors of HIV-MDR were analyzed by taking into account cumulative GRTs. Among 15,628 isolates from 6,802 patients, resistance to at least one drug class decreased sharply from 1998 to 2010 (1998-2001:78%; 2008-2010:59%; p<0.001) and then remained relatively constant at around 50% over 2011-2018, with a proportion of isolates with HIV-MDR also stable (around 9%). By evaluating factors associated with cumulative HIV-MDR, in the multivariable model male gender, sexual and vertical transmission, number of previous PIs, NRTIs, NNRTIs, previous exposure to INSTI, enfuvirtide and maraviroc and co-infection with HBV were associated with an increased risk of HIV-MDR. By contrast, a Nadir CD4 ≥200 cells/mm3 starting ART from 2008 and co-infection with HCV were associated with a lower risk of HIV-MDR. In conclusion, this study revealed that HIV-1 drug resistance has been stable since 2011 despite its dramatic decrease over the last two decades. HIV-MDR is still present, although at a lower rate, suggesting the need for continuous surveillance and accurate management of HIV-infected ART-experienced patients.