# HIV-1 virologic failure in the RESINA cohort: lessons from two decades of real-world data

## TL;DR

This study analyzed real-world data from 2001 to 2024 to understand HIV treatment failure, its predictors, resistance patterns, and recovery times in a large cohort.

## Contribution

The study provides insights into long-term trends in HIV virologic failure and resistance patterns across different treatment eras.

## Key findings

- Virologic failure rates declined over time, from 4.7% in 2001–2007 to 1.7% in 2014 and later.
- Multiclass drug resistance was common at failure, but INSTI resistance remained rare.
- INSTI-based regimen switches were associated with consistent resuppression and no multiclass resistance.

## Abstract

To quantify virologic failure (VF), identify predictors, characterize resistance patterns at failure, and evaluate time to resuppression in the RESINA cohort.

ART-naïve adults initiating ART in 2001–2024 were followed. VF was defined as at least one HIV-1 RNA > 200 copies/mL after suppression or ≥ 0.5-log₁₀ rebound. Participants were grouped by treatment era (2001–2007, 2008–2013, ≥ 2014), reflecting availability of drug classes. Genotypes at baseline and VF were interpreted using the HIV-GRADE algorithm. Predictors of VF were assessed with logistic regression; time to resuppression (< 50 copies/mL) after first VF with Cox models and Kaplan–Meier plots.

Among 5136 participants, 139 (2.7%) had VF; rates declined across eras (4.7%, 2.6%, 1.7%). Independent predictors were injection-drug use (OR 1.74), CD4 < 200/µL (OR 2.32), and ART start in 2001–2007 (OR 1.95); MSM acquisition was protective (OR 0.32). At failure, 36 patients showed resistance, often multiclass (61%); INSTI resistance was rare (n = 5). After first VF, 122/139 cases resuppressed (median 147 days). Male sex predicted faster resuppression (HR 1.81); higher failure VL trended to slower resuppression (HR 0.84 per log₁₀). INSTI-based switches consistently achieved resuppression in descriptive analyses and were not associated with multiclass resistance.

VF was uncommon and declined over time, reflecting improved regimen potency and tolerability. Failures were associated with late presentation and IDU, consistent with adherence barriers. Resistance often involved multiple classes, while INSTI resistance remained infrequent. Early, genotype-guided optimization, preferably to INSTI-based therapy, combined with targeted adherence support may improve outcomes.

The online version contains supplementary material available at 10.1007/s15010-025-02713-7.