HIV treatment with dolutegravir and doravirine: rationale for selection and clinical outcomes in a highly treatment experienced population

Abstract

Dolutegravir and doravirine are individually safe and effective antiretroviral therapy (ART) components, but their combined use has not been studied in clinical trials and is not recommended in HIV treatment guidelines. We noted persons with HIV (PWH) receiving dolutegravir with doravirine at our Washington, DC, infectious disease clinic and undertook a service evaluation to understand why providers selected this ART, whether HIV virologic suppression was achieved and identify adverse effects of concomitant use. Case registry and prescriptions data identified 21 PWH receiving concomitant dolutegravir and doravirine with mean follow-up 576.1 days (range 413–751); frequent reasons for switching were multiple ART resistance (57.1%), proton pump inhibitor usage (28.6%) and renal failure (28.6%), with 52.4% switched from protease inhibitor or cobicistat-boosted regimens. Dolutegravir with doravirine alone was prescribed for 60%, and additional ART in 40%. During 12 months follow-up mean CD4 was 585.9 (baseline 570.7) with undetectable viral load in 77.8% (baseline 66.7%). No discontinuations for drug-related adverse events or virologic failure occurred. Dolutegravir with doravirine was well tolerated in small numbers of highly treatment experienced PWH at our clinic, achieving virologic suppression in most. Establishing the efficacy and safety of dolutegravir with doravirine for HIV treatment in randomized trials remains important.

The DoDo Experience: An Alternative Antiretroviral 2-Drug Regimen of Doravirine and Dolutegravir

“…The characteristics of PLH on DOR + DTG observed in this study indicating older ager and extensive previous ART experience, the main reasons for switching, as well as the so far favorable course of treatment are in accordance with anecdotal reports and also two smaller observational studies of 18 PLH from Italy [12] and 12 PLH from Washington, DC [11] who switched to a 2DR of DOR + DTG, all at ≥ 50 years of age.…”

“…However, despite being a theoretically attractive and both FDA-and EMA-approved combination, DOR + DTG has not been speci cally studied in any randomized trial. Even observational data remain scarce [11,12]. The objective of this study was to establish a rst "real-world" evidence base for the use of DOR + DTG as a 2DR.…”

The DoDo experience: an alternative antiretroviral 2-drug regimen of doravirine and dolutegravir

“…The characteristics of PLWH on DOR + DTG observed in this study indicating older ager and extensive previous ART experience, the main reasons for switching, as well as the so far favorable course of treatment are in accordance with anecdotal reports and also two smaller observational studies of 18 PLWH from Italy [16] and 12 PLWH from Washington, DC [15] who switched to a 2DR of DOR + DTG, all at ≥ 50 years of age.…”

“…However, despite being a theoretically attractive and both FDA-and EMA-approved combination, DOR + DTG has not been specifically studied in any randomized trial. Even observational data remain scarce [15,16]. The objective of this study was to establish a first "real-world" evidence base for the use of DOR + DTG as a 2DR.…”

Real-Life Experience on Dolutegravir and Lamivudine as Initial or Switch Therapy in a Silver Population Living with HIV

“…Regarding DTG/DOR, we do not at this time have randomized clinical trials, but evidence has come mostly from observational and real-life cohorts [ 31 , 32 , 33 ]. In comparison with DTG/RPV and DTG/3TC, and despite this regimen not being mentioned in the guidelines, DTG/DOR is used mostly in highly treated PLWH to build a maintenance therapy with no drug–drug interactions and with a high genetic barrier [ 34 ]. However, DTG/3TC remains to date the only dual treatment approved by guidelines both in naïve and experienced PLWH, and with the longest follow-up and the most robust data [ 12 , 13 , 14 , 15 , 16 , 17 , 18 ].…”