Characterization and outcomes of difficult-to-treat patients starting modern first-line ART regimens: Data from the ICONA cohort

Objectives: Treatment failures to modern antiretroviral therapy (ART) raise concerns, as they could re-duce future options. Evaluations of occurrence of multiple failures to modern ART are missing and their significance in the long run is unclear.Methods: People with HIV (PWH) in the ICONA cohort who started a modern first-line ART were defined as 'difficult to treat' (DTT) if they experienced >= 1 among: i)>= 2 VF (2 viral loads, VL > 200 copies/mL or 1 VL > 10 0 0 copies/mL) with or without ART change; ii) >= 2 treatment discontinuations (TD) due to toxic-ity/intolerance/failure; iii) >= 1 VF followed by ART change plus >= 1 TD due to toxicity/intolerance/failure. A subgroup of the DTT participants were matched to PWH that, after the same time, were non-DTT. Treat-ment response, analysing VF, TD, treatment failure, AIDS/death, and SNAE (Serious non-AIDS event)/death, were compared. Survival analysis by KM curves and Cox regression models were employed.Results: Among 8061 PWH, 320 (4%) became DTT. Estimates of becoming DTT was 6.5% (95% CI: 5.8- 7.4%) by 6 years. DTT PWH were significantly older, with a higher prevalence of AIDS and lower CD4 + at nadir than the non-DTT. In the prospective analysis, DTT demonstrated a higher unadjusted risk for all the outcomes. Once controlled for confounders, significant associations were confirmed for VF (aHR 2.23, 1.33-3.73), treatment failure (aHR 1.70, 1.03-2.78), and SNAE/death (aHR 2.79, 1.18-6.61). Conclusion: A total of 6.5% of PWH satisfied our definition of DTT by 6 years from ART starting. This appears to be a more fragile group who may have higher risk of failure.(c) 2023 The Author(s). Published by Elsevier Ltd.

Automated summary

This study evaluated multiple treatment failures to modern antiretroviral therapy in HIV-infected individuals and found that approximately 4% of them were difficult to treat. The difficult to treat group, compared to the non-difficult to treat group, was characterized by older age, higher prevalence of AIDS, lower CD4+ cell count, and higher risk of treatment failure.