Advances in potency and resistance barrier of antiretroviral drugs for HIV infection and evidence from recent randomized clinical trials (RCTs) support the use of dual therapy at least in specific patient populations. Both, Dolutegravir (DTG) and boosted darunavir (bDRV) are potent antiretroviral drugs with a high resistance barrier. DUALIS, a phase IIIb, open-label RCT demonstrated non-inferiority of a switch to DTG+bDRV (2DR) versus continuous 2NRTI+bDRV (3DR) in virologically suppressed people living with HIV (PLWH) with week 48 virologic response rates of 86% (2DR) and 88% (3DR).
Post-hoc analysis of virologic outcomes in DUALIS with respect to treatment history and HIV drug resistance. Among study inclusion criteria was an HIV-RNA level <50 cps/mL for ≥24 weeks (one blip accepted); any history/presence of drug resistance other than INSTI or bDRV was not exclusionary. Documentation of resistance-associated mutations (RAMs) was based on the Stanford HIVdb mutation list involving specific additional RAMs. Virologic outcomes in subgroups include the primary endpoint (PE, i.e. % with HIV-RNA<50cps/mL at week 48) and % of patients with ≥50 cps/mL (i.e. data in window and ≥50 cps/mL or discontinuation for lack of efficacy or discontinuation for other reason and ≥50 cps/mL).
The ITTe set included 263 subjects (2DR n=131, 3DR n=132): 90.1% males, median age 48 years, CDC stage C 29.7%, CD4 nadir<200/µl 47.0%; median time on ART 5.3 years, 27.4% with ≥2 ART changes, 8.4% with prior INSTI use; 20.9% and 11.0% had a history of ≥2 NRTI and ≥2 PI changes, respectively. NRTI, NNRTI and (minor or major) PI RAMS were observed in 9.1, 12.9, and 26.6% (major PI RAMS 3.4%), respectively. Resistance categories and PE analyses within subgroups are shown in Table 1 with response rates ≥80% across groups. Response rates with major and/or minor RAMs were 88.9% on 2DR and 95.5% on 3DR versus 84.9% (2DR) and 84.1% (3DR) without documented RAMs. No patient with major/minor RAMs in either group had ≥50 HIV-RNA cps/mL at last follow-up. No emergence of RAMs during follow-up was observed.
As shown in the DUALIS study, dual therapy with DTG+bDRV tends to be an effective treatment option with no treatment-emergent resistance for PLWH on suppressive first- or further-line ART with or without evidence of pre-existing NRTI, NNRTI or PI RAMs.