While most HIV-1 patients starting antiretroviral therapy (ART) in recent years achieve and maintain undetectable viral load, patients with a long ART history and failure of multiple therapy lines may have accumulated substantial drug resistance, challenging the possibility for virus control both at individual and population level. However, the prevalence of patients harboring virus with resistance to the four main drug classes (4CR) is largely unknown.
From the EuResist database, we selected treated patients with protease, reverse transcriptase and integrase genotype information available at one or more time points. HIV-1 sequences were interpreted by the Stanford HIVdb 8.8 algorithm and cumulative scores were generated at each sequencing time point. 4CR was defined as high-level resistance to at least one drug in each of the four classes. The frequency of 4CR at each calendar year was estimated as the number of unique patients with 4CR divided by the number of unique patients with at least one sample, up to that year.
Complete four classes HIV-1 genotype information was available from 2643 distinct patients on ART contributing 3544 genotype data from Italy (49.9%), Germany (24.7%), Portugal (8.1%), Luxembourg (7.5%), Sweden (7.0%) and Belgium (2.7%). 66% were male and risk groups included 45.3% MSM, 18.6% drug users and 18.3% heterosexuals. Subtype B virus was harbored by 70.1% of patients and the most prevalent non-B subtypes were G (14.0%) and A1 (7.5%). Overall, 65 patients (2.5%) had 4CR. The prevalence of 4CR declined from 5.6% [95%CI: 1.6-13.8] in 2008 to 2.4% [95%CI: 1.8-3.1] in 2018 (P <0.001, chi-square test for trend; see figure). Patients with 4CR were older (49+/-12 vs. 46+/-11, P = 0.001) and harbored more often subtype B virus (85.3% vs. 69.7%, P = 0.013) with respect to patients without 4CR. No association was demonstrated between 4CR and gender or risk groups.
In a large population of patients across Europe with complete HIV-1 genotype information, the prevalence of 4CR appears to be relatively low and possibly declining over recent years. Continuous surveillance of this challenging population is warranted to provide effective treatment at the individual level and define factors predicting accumulation of resistance over time.