Dolutegravir-based Dual Therapies in HIV-infected Patients With Virological Suppression (DOLBI)

The Efficacy and Safety of Dolutegravir-based Dual Therapies in HIV-infected Patients With Intolerance or Toxicity to Nucleoside Analogues

The objective of this study was to evaluate the efficacy and safety, and evolution of causes leading to change, of dual therapies based in Dolutegravir in patients requiring a change of virologically effective antiretroviral therapy.

Study Overview

• Status: Completed
• Conditions: HIV Infection
• Intervention / Treatment: Other: Dolutegravir in a dual therapy regimen

Detailed Description

Despite the high rate of virological suppression and low risk of toxicity, HIV-infected patients continue to need new antiretroviral strategies, such as dual therapies, because of different end-organ involvement (kidney, bone, cardiovascular..), intolerance or toxicity. To date, only a protease inhibitor (PI)-based regimen was able to permit the use of dual therapies (two antiretrovirals), especially in case of patients with history of virological failure to other regimens. However, the recent license of Dolutegravir, a integrase inhibitor with high genetic barrier, could help to clinicians to manage patients with intolerance or toxicity to nucleoside analogues without putting in risk virological suppression.

• Study Type: Observational
• Enrollment (Actual): 155

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain, 28034
    • Ramón y Cajal Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

HIV-infected patients who had initiate a dolutegravir-based dual therapy because of intolerance or toxicity to nucleoside analogues

Description

Inclusion Criteria:

• Older than 18 years
• Receiving a virologically effective antiretroviral regimen
• Switching to a dual therapy based in dolutegravir because of intolerance or toxicity to nucleoside analogues

Exclusion Criteria:

• Pregnant women
• Receiving other investigational drugs
• Recent diagnosis of opportunistic infection (< 1 month)

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy, measured as maintenance of virological suppression, after switching to a dolutegravir-based dual therapy	Percent of patients remaining with HIV RNA level below 50 copies/ml, according to a missing=failure criteria	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety according to DAIDS grade events 2009 of dual therapy based in dolutegravir	To collect adverse events (according to DAIDS grade events, 2009) and rate of discontinuation related with adverse events, of dual therapy after switching	12 months
Outcome of causes leading to switch the previous regimen	Evolution of causes de change: glomerular filtration rate during evolution, tubular dysfunction (proteinuria, phosphaturia, glycosuria, uricosuria),bone mineral density by DXA (dual X-ray absorptiometry), lipid disorders, adherence	12 months
Efficacy, measured as maintenance of virological suppression, of different dual therapies with dolutegravir	Comparison of efficacy (HIV RNA level < 50 c/ml) of the different dolutegravir-based dual therapies, according to accompanying drug (non nucleoside, especially rilpivirine), protease inhibitors (darunavir boosted with ritonavir or cobicistat), or nucleoside analogues (lamivudine).	12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of virological suppression in patients with previous failure to more than 2 families of antiretroviral drugs	Effect of extended previous failure, or mutations in the transcriptase and protease gene, in the rate of virological suppression in dolutegravir-based dual therapies	12 months

Collaborators and Investigators

• Sponsor: Asociacion para el Estudio de las Enfermedades Infecciosas
• Investigators: Principal Investigator: Jose L Casado, MD, PhD, Ramón y Cajal Hospital

Publications and helpful links

General Publications

• Casado JL, Monsalvo M, Fontecha M, Vizcarra P, Rodriguez MA, Vivancos MJ, Moreno S. Dolutegravir plus rilpivirine as dual regimen in virologically suppressed HIV-1 infected patients in a clinical setting. HIV Res Clin Pract. 2019 Apr;20(2):64-72. doi: 10.1080/15284336.2019.1628460. Epub 2019 Jun 19.
• Vizcarra P, Fontecha M, Monsalvo M, Vivancos MJ, Rojo A, Casado JL. Efficacy and safety of dolutegravir plus boosted-darunavir dual therapy among highly treatment-experienced patients. Antivir Ther. 2019;24(6):467-471. doi: 10.3851/IMP3319.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2015
• Primary Completion (Actual): March 1, 2018
• Study Completion (Actual): June 1, 2018

Study Registration Dates

• First Submitted: June 28, 2015
• First Submitted That Met QC Criteria: July 2, 2015
• First Posted (Estimate): July 8, 2015

Study Record Updates

• Last Update Posted (Actual): July 2, 2018
• Last Update Submitted That Met QC Criteria: June 29, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: HIV; dolutegravir; intolerance; dual therapies
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; HIV Integrase Inhibitors; Integrase Inhibitors; Dolutegravir
• Other Study ID Numbers: Dolbi

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED