Background: Treatment failures to modern ART regimens are of concern, as they might limit future drug options leading to clinical failure. Real-world estimates of the rate of multiple failures to modern regimens are lacking and long-term consequences remain unclear. Material and methods: Participants of the ICONA cohort who started a modern first-line ART (2NRTI+DRV/b; 2NRTI+INSTI; 2NRTI+RPV; 2NRTI+DOR; DTG+3TC) were included. Patients were classified as ’difficult to treat’ (DTT) if, after starting ART, experienced ≥1of these events: i)≥2 VF (VF defined as two consecutive viral load (VL)>50 copies/mL) with or without subsequent ART change; ii)≥2 treatment discontinuations (TD) due to toxicity/intolerance/failure; iii)≥1 VF followed by ART change plus≥1 TD due to toxicity/intolerance/failure. Time to first fulfilling the DTT definition was estimated using the Kaplan-Meier (KM). We then identified PLWHIV who, after the same time from starting ART, were still free from DTT events. In a subset of these who subsequently initiated a new regimen, we compared the treatment response between DTT and matched unexposed analysing the following endpoints: a) VF; b) TD due to intolerance/toxicity/failure; c) treatment failure (composite of VL>200 copies/mL or TD forintolerance/toxicity/failure); and d) clinical failure [AIDS/death, SNAE (serious non-AIDS event)/death]. Survival analysis by means of KM curves and Cox regression models were employed. Results: Among 8061 PLWHIV included, 320 (4%) entered in the DTT definition. KM probability of becoming DTT was 6.5% (5.8 to7.4%) by 6 years. DTT PLWHIV had a significantly higher prevalence of AIDS diagnosis, were slightly older, had lower nadir of CD4, had higher VL at ART starting, when compared to the non-DTT PLWHIV (Table 1). In unadjusted analyses and compared to the matched unexposed group (286 DTT and 572 matched-unexposed), DTT showed higher probabilities of experiencing all the outcomes. After controlling for confounders, the associations remained significant for VF, treatment failure, SNAE/death (Figure 1). Conclusions: A total of 6.5% of PLWHIV who started a modern first-line ART satisfied our arbitrary definition of DTT by 6 years from ART initiation. This appears to be a more vulnerable PLWHIV population who may experience a higher risk of treatment and clinical failure in the long term.

Characterisation and outcomes of difficult-to-treat patients in an Italian cohort of PLWHIV starting modern ART regimens.

Costantini A;
2022

Abstract

Background: Treatment failures to modern ART regimens are of concern, as they might limit future drug options leading to clinical failure. Real-world estimates of the rate of multiple failures to modern regimens are lacking and long-term consequences remain unclear. Material and methods: Participants of the ICONA cohort who started a modern first-line ART (2NRTI+DRV/b; 2NRTI+INSTI; 2NRTI+RPV; 2NRTI+DOR; DTG+3TC) were included. Patients were classified as ’difficult to treat’ (DTT) if, after starting ART, experienced ≥1of these events: i)≥2 VF (VF defined as two consecutive viral load (VL)>50 copies/mL) with or without subsequent ART change; ii)≥2 treatment discontinuations (TD) due to toxicity/intolerance/failure; iii)≥1 VF followed by ART change plus≥1 TD due to toxicity/intolerance/failure. Time to first fulfilling the DTT definition was estimated using the Kaplan-Meier (KM). We then identified PLWHIV who, after the same time from starting ART, were still free from DTT events. In a subset of these who subsequently initiated a new regimen, we compared the treatment response between DTT and matched unexposed analysing the following endpoints: a) VF; b) TD due to intolerance/toxicity/failure; c) treatment failure (composite of VL>200 copies/mL or TD forintolerance/toxicity/failure); and d) clinical failure [AIDS/death, SNAE (serious non-AIDS event)/death]. Survival analysis by means of KM curves and Cox regression models were employed. Results: Among 8061 PLWHIV included, 320 (4%) entered in the DTT definition. KM probability of becoming DTT was 6.5% (5.8 to7.4%) by 6 years. DTT PLWHIV had a significantly higher prevalence of AIDS diagnosis, were slightly older, had lower nadir of CD4, had higher VL at ART starting, when compared to the non-DTT PLWHIV (Table 1). In unadjusted analyses and compared to the matched unexposed group (286 DTT and 572 matched-unexposed), DTT showed higher probabilities of experiencing all the outcomes. After controlling for confounders, the associations remained significant for VF, treatment failure, SNAE/death (Figure 1). Conclusions: A total of 6.5% of PLWHIV who started a modern first-line ART satisfied our arbitrary definition of DTT by 6 years from ART initiation. This appears to be a more vulnerable PLWHIV population who may experience a higher risk of treatment and clinical failure in the long term.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11566/307481
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