Transmitted drug resistance to antiretroviral drugs in Spain during the period 2019–2021

Abstract

HIV; Clinical resistance; Transmission

VIH; Resistencia clínica; Transmisión

VIH; Resistència clínica; Tansmissió

To evaluate the prevalence of transmitted drug resistance (TDR) to nucleoside and nonnucleoside reverse transcriptase inhibitors (NRTI, NNRTI), protease inhibitors (PI), and integrase strand transfer inhibitors (INSTI) in Spain during the period 2019–2021, as well as to evaluate transmitted clinically relevant resistance (TCRR) to antiretroviral drugs. Reverse transcriptase (RT), protease (Pro), and Integrase (IN) sequences from 1824 PLWH (people living with HIV) were studied. To evaluate TDR we investigated the prevalence of surveillance drug resistance mutations (SDRM). To evaluate TCRR (any resistance level ≥ 3), and for HIV subtyping we used the Stanford v.9.4.1 HIVDB Algorithm and an in-depth phylogenetic analysis. The prevalence of NRTI SDRMs was 3.8% (95% CI, 2.8%–4.6%), 6.1% (95% CI, 5.0%–7.3%) for NNRTI, 0.9% (95% CI, 0.5%–1.4%) for PI, and 0.2% (95% CI, 0.0%–0.9%) for INSTI. The prevalence of TCRR to NRTI was 2.1% (95% CI, 1.5%–2.9%), 11.8% for NNRTI, (95% CI, 10.3%–13.5%), 0.2% (95% CI, 0.1%–0.6%) for PI, and 2.5% (95% CI, 1.5%–4.1%) for INSTI. Most of the patients were infected by subtype B (79.8%), while the majority of non-Bs were CRF02_AG (n = 109, 6%). The prevalence of INSTI and PI resistance in Spain during the period 2019–2021 is low, while NRTI resistance is moderate, and NNRTI resistance is the highest. Our results support the use of integrase inhibitors as first-line treatment in Spain. Our findings highlight the importance of ongoing surveillance of TDR to antiretroviral drugs in PLWH particularly with regard to first-line antiretroviral therapy.

This work is supported in part by grants from Plan Nacional de I+D+I and Fondo Europeo de Desarrollo Regional-FEDER (www.redes/redes/inicio) (RD16/0025/0040; RD16/0025/0026), Fundacion Progreso y salud, Junta de Andalucia (http://www.juntadeandalucia.es/fundacionprogresoysalud/es) (PI- 0550-2017), FIS PI 18/00819 and FIS PI 22/00882; Centro de Investigación Biomédica en Red (CIBER 21/13/00088). Adolfo de Salazar and Ana Fuentes are supported by “Instituto de Salud Carlos III” (grant number CM20/00016 and CM21/00060, respectively).