Ignite Creation Date:
2025-12-25 @ 3:07 AM
Ignite Modification Date:
2026-01-04 @ 11:20 AM
Study NCT ID:
NCT02486133
Status:
COMPLETED
Last Update Posted:
2023-11-29
First Post:
2015-06-15
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Dual Therapy With Boosted Darunavir + Dolutegravir
Sponsor:
Technical University of Munich
Organization:
Study Overview
Official Title:
A Prosp., Multic., Randomized, Open-label Trial to Assess the Safety, Tolerability and Efficacy of Dual Therapy With Boosted Darunavir + Dolutegravir When Switching From SOC ART in HIV-patients With Sustained Virological Suppr.
Status:
COMPLETED
Status Verified Date:
2019-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
Dualis
Brief Summary:
A switch strategy to investigate whether a dual therapy with Ritonavir-boosted (RTV) Darunavir (DRV) + Dolutegravir (DTG) over 48 weeks is non-inferior to a continuous standard of care therapy with RTV-boosted DRV in combination with 2 Nucleosidic Reverse Transcriptase Inhibitors (NRTIs) in HIV patients, who are on a stable antiretroviral therapy (ART) with RTV-boosted DRV in combination with 2 NRTIs.
Detailed Description:
Modern combination antiretroviral therapy (cART) leads to well-controlled HIV infection with a potentially normal life expectancy. Nucleosidic reverse transcriptase inhibitors (NRTIs) play a major role as "ART backbone" and are essential antiretroviral agents according to current European and WHO HIV treatment guidelines. However, NRTI use can be associated with substantial side effects, e.g. bone and kidney toxicity, lipotoxicity and mitochondrial toxicity and can put patients at serious risk. Especially long-term NRTI-exposure is a risk factor for these often cumulative side effects, since the standard of care (SOC) therapy with the different NRTIs consists of the combination of multiple substances. Furthermore NRTI resistances may emerge over time and limit treatment options for pre-treated HIV patients.
As a consequence, alternative NRTI free (so called "nuke sparing") therapy options have been evaluated in different studies but were associated with less virologic therapeutic success and higher rates of therapy induced resistance compared to standard regimens in ART naïve patients. This is particularly true for patients with a high baseline viral load.
As an alternative to NRTI-based therapy options, Ritonavir-boosted protease inhibitor (PI/r)-based nuke-sparing dual therapies have been studied widely, mostly in combination with the integrase inhibitor (INI) Raltegravir (RAL). In this setting, the PI was not fully capable to prevent the development of INI resistant viruses.
The HIV protease inhibitor Darunavir (DRV) and the novel INI Dolutegravir (DTG) are both very potent anchor drugs with a high barrier to resistance. Due to a favourable side-effect profile, a once-daily (QD) formulation and its virological potency, DRV is currently one of the most frequently used PIs in Europe and the USA. In addition, the new, once-daily administrable integrase inhibitor DTG showed an excellent tolerability profile as well as a high resistance barrier.
The nuke-free combination of DTG (50 mg) with the Ritonavir (/r)- or Cobicistat-boosted protease inhibitor DRV (800 mg) may offer a favorable safety and efficacy profile with the advantage of QD-dosing.
As a consequence, alternative NRTI free (so called "nuke sparing") therapy options have been evaluated in different studies but were associated with less virologic therapeutic success and higher rates of therapy induced resistance compared to standard regimens in ART naïve patients. This is particularly true for patients with a high baseline viral load.
As an alternative to NRTI-based therapy options, Ritonavir-boosted protease inhibitor (PI/r)-based nuke-sparing dual therapies have been studied widely, mostly in combination with the integrase inhibitor (INI) Raltegravir (RAL). In this setting, the PI was not fully capable to prevent the development of INI resistant viruses.
The HIV protease inhibitor Darunavir (DRV) and the novel INI Dolutegravir (DTG) are both very potent anchor drugs with a high barrier to resistance. Due to a favourable side-effect profile, a once-daily (QD) formulation and its virological potency, DRV is currently one of the most frequently used PIs in Europe and the USA. In addition, the new, once-daily administrable integrase inhibitor DTG showed an excellent tolerability profile as well as a high resistance barrier.
The nuke-free combination of DTG (50 mg) with the Ritonavir (/r)- or Cobicistat-boosted protease inhibitor DRV (800 mg) may offer a favorable safety and efficacy profile with the advantage of QD-dosing.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: