Boosted Darunavir and Dolutegravir Dual Therapy among a Cohort of Highly Treatment-Experienced Individuals

Abstract

Background: The use of dual antiretroviral therapy (ART) regimens for treatment of HIV is increasing. The contemporary combination of boosted darunavir with dolutegravir has not been widely studied. Methods: This was a retrospective cohort study that evaluated treatment-experienced individuals within three large urban clinics prescribed boosted darunavir with dolutegravir (study regimen) dual therapy. Follow-up was defined as the number of days from regimen initiation until the last HIV RNA determination on the study regimen. Virological outcomes, HIV RNA ≤50 copies/ml (undetectable), were assessed overall and by baseline HIV RNA status. Results: Of 65 individuals included, 83% were at least 3-class antiretroviral-experienced and median time since starting ART was 19 years (IQR 13-22). Median followup was 419 days (IQR 286-744). An undetectable HIV RNA was achieved by 62/65 (95%) individuals at any time point on the study regimen. At the end of followup 61/65 (94%) individuals remained undetectable, including 48/49 (98%) with an undetectable HIV RNA at baseline (those changing for optimization) and 13/16 (81%) with viraemia at baseline (those changing therapy during virological failure). At the end of follow-up, 55 (85%) individuals were still taking the study regimen. No individuals stopped therapy due to virological failure or intolerance. Conclusions: In a highly treatment-experienced cohort, boosted darunavir with dolutegravir dual therapy demonstrated high rates of virological success, even in those with detectable HIV RNA prior to initiating the study regimen. Further study of this potent, simple, high-barrier dual-class regimen is warranted.

Virological response and resistance profile in highly treatment‐experienced HIV‐1‐infected patients switching to dolutegravir plus boosted darunavir in clinical practice

“…Despite the limited sample size, the randomized DUALIS study showed that switching to DTG + bDRV was non-inferior to continuing boosted DRV plus two NRTIs [11]. Likewise, the efficacy of DTG + bDRV reported in other observational studies among viraemic patients was promising [12,13,15,17], confirming the attractiveness of this option. However, despite this high efficacy, our results showed that patients receiving a non-fully active regimen showed a lower probability of VS (80.0%), suggesting that careful review of GRT results must also be considered.…”

“…Nowadays, DTG + bDRV regimen is mainly prescribed in highly treatment-experienced patients and with high prevalence of MRMs, not only in the NRTI class, but also in the PI class [12,[14][15][16].…”

“…So far, only one clinical trial has investigated a 2DR switch based on DTG + bDRV, in which individuals having documented major DRV or INI resistance were excluded [11]. The observational studies reporting this combination had a limited sample size, and frequently showed partial information about previous drug resistance [12][13][14][15][16][17][18]. Based on these considerations, we evaluated the virological response and resistance profile in cART-experienced HIV-1-infected individuals in Italy starting dual therapy with DTG + bDRV for the first time.…”

Virologic outcomes of switching to boosted darunavir plus dolutegravir with respect to history of drug resistance

“…Real-word data are in line with the results of this study. Several cohort studies evaluating bDRV plus DTG in PLWH with extended treatment experience and an even higher prevalence of NRTI, NNRTI, and major PI RAMs than in the DUALIS study confirmed a high virologic effectiveness and a high resistance barrier of the dual regimen [12][13][14][15]. In a small retrospective cohort study, 49 of 50 PLWH (98%) maintained viral suppression on bDRV and DTG for a median of 25 months without the emergence of new RAMs [14].…”

A novel HIV-1 protease inhibitor, GRL-044, has potent activity against various HIV-1s with an extremely high genetic barrier to the emergence of HIV-1 drug resistance

“…In the present work, we designed, synthesized, and identified two novel nonpeptidic HIV-1 protease inhibitors (PIs), GRL-037 and GRL-044, containing (i) P2-tetrahydropyrano-tetrahydrofuran (Tp-THF), (ii) P1-benzene and P1-methoxybenzene, respectively, and (iii) P2'-isopropyl-aminobenzothiazole (Ip-Abt) on the structure of darunavir (DRV) (7,8), which is the last approved PI for the treatment of HIV-1 infection/AIDS and has been most used worldwide (8)(9)(10). Both GRL-037 and GRL-044 showed potent antiviral activity against wild-type HIV-1, but GRL-044, in particular, exerted potent antiviral activity against wild-type HIV-1, HIV-2, and various drug-resistant HIV-1 variants.…”