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

• ClinicalTrials.gov Identifier: NCT02491242
• Recruitment Status: Completed
• First Posted: July 8, 2015
• Last Update Posted: July 2, 2018
• Sponsor: Asociacion para el Estudio de las Enfermedades Infecciosas
• Information provided by (Responsible Party): Jose L. Casado, Asociacion para el Estudio de las Enfermedades Infecciosas

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment
HIV Infection	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 Design

• Study Type: Observational [Patient Registry]
• Actual Enrollment: 155 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Target Follow-Up Duration: 12 Months
• Official Title: The Efficacy and Safety of Dolutegravir-based Dual Therapies in HIV-infected Patients With Intolerance or Toxicity to Nucleoside Analogues
• Actual Study Start Date: November 2015
• Actual Primary Completion Date: March 2018
• Actual Study Completion Date: June 2018

Groups and Cohorts

Intervention Details:

• Other: Dolutegravir in a dual therapy regimen
  None. Patients initiating Dolutegravir-based dual therapy because of nucleoside analogues toxicity or intolerance will be followed up during a year

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Safety according to DAIDS grade events 2009 of dual therapy based in dolutegravir [ Time Frame: 12 months ]
   To collect adverse events (according to DAIDS grade events, 2009) and rate of discontinuation related with adverse events, of dual therapy after switching
2. Outcome of causes leading to switch the previous regimen [ Time Frame: 12 months ]
   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
3. Efficacy, measured as maintenance of virological suppression, of different dual therapies with dolutegravir [ Time Frame: 12 months ]
   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).

Other Outcome Measures:

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

Eligibility Criteria

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

Criteria

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)

Contacts and Locations

Locations

Spain

Ramon y Cajal Hospital

Madrid, Spain, 28034

Sponsors and Collaborators

Asociacion para el Estudio de las Enfermedades Infecciosas

Investigators

• Principal Investigator: Jose L Casado, MD, PhD; Ramon y Cajal Hospital

More Information

Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Jose L. Casado, Physician, MD, PhD, Asociacion para el Estudio de las Enfermedades Infecciosas
• ClinicalTrials.gov Identifier: NCT02491242
• Other Study ID Numbers: Dolbi
• First Posted: July 8, 2015
• Last Update Posted: July 2, 2018
• Last Verified: June 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Keywords provided by Jose L. Casado, Asociacion para el Estudio de las Enfermedades Infecciosas:

HIV; dolutegravir; intolerance; dual therapies

Additional relevant MeSH terms:

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Dolutegravir; HIV Integrase Inhibitors; Integrase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anti-HIV Agents; Anti-Retroviral Agents; Antiviral Agents; Anti-Infective Agents