Beyond Surveillance Mutations: Long-Term Trends and Clinical Relevance of Transmitted HIV Drug Resistance in Spain (2007-2023)

Abstract

BACKGROUND: While surveillance drug resistance mutations (SDRMs) remain essential for monitoring transmitted drug resistance (TDR), the clinical impact of transmitted resistance for current first-line regimens has become increasingly important. We aimed to update estimates of TDR in Spain and assess its clinical impact over time. METHODS: This is a nationwide observational study within the CoRIS cohort. We estimated the prevalence of SDRMs and clinically meaningful resistance (CMR) among antiretroviral therapy (ART)-naïve individuals with baseline genotypic resistance testing in 2022-2023 and evaluated annual trends in CMR to first-line regimens from 2007 to 2023. Clinically meaningful resistance was defined as Stanford HIVDB resistance level ? 3. RESULTS: In 2022-2023, 1028 individuals were included; 82.8% were male, 63.2% MSM, and 72.2% subtype B. Surveillance drug resistance mutation prevalence was 14.4% (95% CI 12.2%-16.9%), driven mainly by NNRTI-SDRMs, while INSTI-SDRMs remained rare [0.5% (95% CI 0.1%-1.5%)]; CMR to recommended first-line regimens was very low. Over 2007-2023, CMR declined markedly, coinciding with adoption of second-generation integrase inhibitors. Rilpivirine-associated resistance mutations were detected in 7.0%, largely due to E138A (4.8%). M184V was detected in 0.8%; 6 of 8 cases occurred in persons with current or prior oral pre-exposure prophylaxis (PrEP), although numbers were small. CONCLUSIONS: In Spain, TDR remains stable, but its clinical impact on first-line regimens has markedly declined. These findings support Test & Treat strategies and immediate ART initiation with contemporary triple- or dual-drug regimens, while highlighting the need for targeted resistance assessment for rilpivirine-containing regimens and further research on prior PrEP exposure and selected NRTI resistance patterns.