Shorter Time to Discontinuation Due to Treatment Failure in People Living with HIV Switched to Dolutegravir Plus Either Rilpivirine or Lamivudine Compared with Integrase Inhibitor-Based Triple Therapy in a Large Spanish Cohort

Abstract

Introduction Standard therapy for HIV treatment has consisted of two nucleoside analogue reverse transcriptase inhibitors (NRTI) paired with a third agent. Use of two-drug regimens (2DR) has been considered for selected patients in part to avoid toxicities associated with the use of NRTIs. This study aimed to compare the real-world outcomes of integrase inhibitor (INSTI)-based three-drug regimens (3DR) versus 2DR of dolutegravir (DTG) + rilpivirine (RPV) or DTG + lamivudine (3TC). Methods All patients in the Spanish VACH cohort switching to INSTI-based 3DR or a 2DR consisting of DTG + RPV or DTG + 3TC between May 2, 2016 and May 15, 2019 were included. Kaplan–Meier curves and Cox proportional hazard models were used to assess time to/risk of discontinuation due to treatment failure (TF) (defined as virologic failure [VF], immunologic failure, or disease progression) and adverse events (AEs). Three secondary analyses were performed: (1) in restricting the analysis to patients who were virologically suppressed (HIV RNA < 50 copies/mL) at switch; (2) matched analysis (2:1, matched by age, sex, number of previous VFs, and line of regimen), and (3) using VF as the primary endpoint in all patients. Results Overall, 5047 3DR and 617 2DR patients were analyzed. Baseline characteristics differed between groups; 2DR patients were older, more treatment experienced, and more likely to be virologically suppressed at switch. Time to discontinuation due to TF was significantly shorter for 2DR ( P = 0.002). The hazard ratio (HR) for discontinuation due to TF on 2DR vs 3DR was 2.33 ( P = 0.003). No difference was observed for time to discontinuation ( P = 0.908) or risk of discontinuation due to AEs (HR = 0.80; P = 0.488). Results were qualitatively similar in virologically suppressed patients, matched analysis, and for VF. Conclusion In the real world, the risks of discontinuation due to TF and VF were more than two times higher in patients switching to DTG-based 2DR than INSTI-based 3DR, with no difference in discontinuation due to AEs. Supplementary Information The online version contains supplementary material available at 10.1007/s40121-022-00630-y.

Switching to dolutegravir plus rilpivirine versus maintaining current antiretroviral therapy regimen in virologically suppressed people with HIV-1 and the Lys103Asn (K103N) mutation: 48-week results from a randomised, open-label pilot clinical trial

“…13,14 Two-drug regimens have been considered partly to avoid the toxicity associated with some NRTIs. 15 The removal of CYP3A and other enzyme inducers, such as etravirine and darunavir, and inhibitors such as ritonavir or cobicistat should reduce DDIs and simplify dosing of comedications for co-morbidities. 16 RPV use specifically, however, introduces food requirements and the avoidance of proton pump inhibitors, a key consideration when using DTG/RPV.…”

Taxa de descontinuação da terapia antirretroviral dupla com dolutegravir mais lamivudina em pessoas vivendo com HIV: uma revisão sistemática

“…Em alguns casos, a taxa de descontinuação desta revisão foi superior a 3-DR com DTG, 3TC e ABC, que apresentou taxa de descontinuação de 10,7% (Baldin et al, 2019a). Contudo, essa taxa de descontinuação é bastante variável entre os estudos presentes na literatura, em alguns casos, o risco de descontinuação é até duas vezes maior em indivíduos que utilizaram a terapia tripla, quando comparada a dupla (Teira et al, 2022). Outros estudos apresentaram a taxa de descontinuação para terapia tripla, similar a encontrada neste estudo para 2-DR, com valores de 13,9% (Fabbiani et al, 2021) e 12,5% (Baldin et al, 2021).…”