Abstract
ObjectiveThe DUALIS study showed that switching to boosted darunavir (bDRV) plus dolutegravir (DTG; 2DR) was non-inferior to continuous bDRV plus 2 nucleoside/nucleotide reverse-transcriptase inhibitors (NRTIs; 3DR) in treatment-experienced virologically suppressed people living with HIV (PLWH). We analyzed virologic outcomes with respect to treatment history and HIV drug resistance.DesignPost hoc analysis of a randomized trial.MethodsMain inclusion criteria were an HIV RNA level < 50 copies/mL for ≥ 24 weeks and no resistance to integrase strand transfer inhibitors or bDRV. Resistance-associated mutations (RAMs) were interpreted using the Stanford HIVdb mutation list. Outcomes measures were 48-week virologic response (HIV RNA < 50 copies/mL, FDA snapshot) and HIV RNA ≥ 50 copies/mL (including discontinuation due to a lack of efficacy or reasons other than adverse events and HIV RNA ≥ 50 copies/mL, referred to as snapshot non-response).ResultsThe analysis population included 263 patients (2DR: 131, 3DR: 132): 90.1% males; median age, 48 years; CD4 + T-cell nadir < 200/µl, 47.0%; ≥ 2 treatment changes, 27.4%; NRTI, non-NRTI (NNRTI), and major protease inhibitor (PI) RAMs in 9.5%, 14.4%, and 3.4%, respectively. In patients with RAMs in the 2DR and 3DR groups, virologic response rates were 87.8% and 96.0%, respectively; the corresponding rates in those without RAMs were 85.7% and 81.8%. RAMs were unrelated to virologic non-response in either group. No treatment-emergent RAMs were observed.ConclusionsDTG + bDRV is an effective treatment option without the risk of treatment-emergent resistance for PLWH on suppressive first- or further-line treatment with or without evidence of pre-existing NRTI, NNRTI, or PI RAMs.Trial registration: EUDRA-CT Number 2015-000360-34; registered 07 April 2015; https://www.clinicaltrialsregister.eu/ctr-search/trial/2015-000360-34/DE.
Highlights
Advances in the potency and resistance barrier of antiretroviral drugs for HIV infection, as well as evidence from recent randomized clinical trials (RCTs) in people living with HIV (PLWH), support the use of dual therapy including a boosted protease inhibitor (PI) or a second-generation integrase strand transfer inhibitor
Treatment history, and HIV drug resistance The ITTe analysis population of the DUALIS study included 263 patients (2DR, n = 131; 3-drug regimen (3DR), n = 132): 90.1% were of male sex; median age, 48 years; Centers for Disease Control category C, 29.7% of patients; and CD4 + T-cell nadir < 200/μL, 47.0% of patients
nucleotide reverse-transcriptase inhibitors (NRTIs), NNRTI, and/or PI Resistance-associated mutations (RAMs) were observed in 9.5%, 14.4%, and 30.0% of the ITTe set, respectively
Summary
(INSTI) in specific patient populations such as PLWH on suppressive antiretroviral therapy (ART) without a history of virologic failure or — at least for some combinations — treatment-naïve PLWH [1,2,3,4] Both the 2nd generation INSTI dolutegravir (DTG) and the PI darunavir (DRV, boosted with ritonavir or cobicistat) have been shown to be potent antiretroviral drugs with a high resistance barrier in treatment-naïve and treatmentexperienced PLWH [5,6,7,8]. The rates of snapshot virologic non-response were 3.8% (2DR) and 5.3% (3DR), with a difference of − 1.4% (95% CI − 6.5 to + 3.6%) [9] In this post hoc analysis of the DUALIS study, historic genotypic resistance patterns were assessed and primary and secondary virologic outcomes in the 2DR and 3DR study arms were evaluated with respect to treatment history and HIV drug resistance
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