EFFICACY AND SAFETY OF A SIMPLIFICATION STRATEGY BASED ON DOLUTEGRAVIR AND DARUNAVIR / COBICISTAT VS OPTIMIZED TREATMENT IN SUPPRESSED HIV-1-INFECTED PATIENTS CARRYING ARCHIVED MULTIDRUG RESISTANCE MUTATIONS

NCT03683524 | Completed Phase 4

• 1 other identifier: Study 2D
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 1

Brief Summary

The availability of antiretroviral therapy has led to a reduction in morbidity and mortality in patients with chronic HIV infection. The treatment, however, is not free of side effects, has potential interactions with other medications, is expensive and can be complex, especially in those patients who are very experienced and with mutations that give them resistance to multiple drugs. For this reason, the development of simplification strategies that avoid unnecessary exposure to antiretroviral agents remains of great interest. This is a simplification study, in which the investigators try to evaluate that with less medication the investigator can maintain the same virological control of the disease. This would mean a lower burden of medication for patients, facilitating its administration and reducing the number of unwanted side effects. Specifically, the investigators intend to evaluate the treatment with Darunavir / cobicistat plus Dolutegravir as a simplification strategy, since both drugs are taken once a day, have a powerful antiviral activity, even against antiretroviral resistant viruses, and are among the best tolerated (with fewer side effects). The results reported in some observational studies suggest that two-drug therapy (bitherapy) as a simplification strategy could also be safe and effective, however, as far as the investigators know, there are no data and clinical trials that specifically evaluate darunavir / cobicistat plus dolutegravir as a strategy of simplification.

Conditions

HIV-1 Infection

Keywords

Simplification strategy; Multidrug resistant; Dolutegravir; Darunavir/cobicistat; Bitherapy

Outcome Measures

Primary Outcomes (1)

• Plasma HIV-1 RNA < 50 copies/mL at 48 weeks

  HIV-1 RNA \< 50 copies/mL using a Time to Loss of Virological Response (TLOVR).

  week 48

Secondary Outcomes (9)

• Percentage of patients developing ART-associated adverse events

  Since baseline to week 48

• Changes in CD4+ cell count

  Since baseline to week 48

• Emergence of new mutations in HIV-1 protease and integrase

  Baseline and in case of virological failure, defined as ≥ 50 copies/mL in 2 consecutive determinations or a single HIV-1 RNA values > 1000 copies/mL. We can observe a virological failure throughout the study (from baseline to week 48)

• Plasma HIV-1 RNA < 50 copies/mL at 24 weeks

  Week 24

• Plasma HIV-1 RNA < 50 copies/mL at 24 and 48 weeks

  Week 24 and 48

Study Arms (2)

Experimental group

EXPERIMENTAL

bitherapy based on DTG (50 mg QD) plus DRV/cobi (800/150 mg QD)

Drug: Dolutegravir (DTG) plus Darunavir/cobicistat (DRV/cobi).

Control group

ACTIVE COMPARATOR

continuation of their current stable ART

Drug: Current ART

Interventions

Dolutegravir (DTG) plus Darunavir/cobicistat (DRV/cobi). DRUG

bitherapy based on DTG (50 mg QD) plus DRV/cobi (800/150 mg QD)

Experimental group

Current ART DRUG

To continue with their current ART

Control group

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• HIV-1 infected patients (≥18 years).
• Confirmed plasma HIV-1 RNA levels \< 50 copies/ml for ≥ 6 months preceding the study randomization.
• Currently ART containing at least 3 antiretroviral drugs (protease inhibitors, non- nucleoside reverse transcriptase inhibitors, integrase inhibitors and CCR5 receptor antagonists on routine clinical practice).
• Must have historical genotyping tests showing DRM associated with at least two antiretroviral classes according to Stanford dB.
• Willing and able to be adherent to their cART regimen for the duration of the study (in opinion of physician).
• Signed informed consent
• condom use nor diaphragma are considered as an additional method of contraception only and cannot be the only method of contraception used as not been considered an effective method by the Clinical Trial Facilitation Group (CTFG) guidelines.

You may not qualify if:

• \. Subjects with any DRM associated to INSTI (i.e. T66I, 74M, E92Q, T97A, F121Y, E138A/K, G140A/S, Y143R/H/C, S147G, Q148H/K/R, N155H AND R263K) in historical genotyping tests. 2. Subjects with any evidence of previous virologic failure to INSTI-based regimens (with or without DRM in the integrase). 3. Subjects who have experienced previous uncontrolled interruptions of INSTI-based regimens. 4. Subjects who have archived DRM conferring a low - or higher - level of resistance to DRV/cobi (\>15 points from Stanford dB score). 5. Subjects with unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), cirrhosis, known biliary abnormalities (apart from hyperbilirubinemia or jaundice due to Gilbert's syndrome or asymptomatic gallstones) 6. Subjects with severe hepatic impairment (class C) according to the Child-Pugh classification 7. Subjects with alanine aminotransferase (ALT) ≥ 5 times upper normal limit (ULN) or ALT ≥ 3 times ULN and bilirubin ≥ 1.5 times ULN. 8. Subjects with hepatitis C co-infection that would require therapy during the study.
• \. Subjects with hepatitis B surface antigen (HBsAg) positive. 10. Known allergy to the study drugs or their components. 11. Current or prior therapy which, in the opinion of the investigators, would make the individual unsuitable for the study or influence the results of the study. 12. Females who are pregnant or breastfeeding

Sponsors & Collaborators

• Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia: lead
• ViiV Healthcare: collaborator

Study Sites (1)

Hospital Germans Trias I Pujol

Badalona, Barcelona, 08916, Spain

Location

Related Publications (1)

• Santos JR, Domingo P, Portilla J, Gutierrez F, Imaz A, Vilchez H, Curran A, Valcarce-Pardeiro N, Payeras A, Bernal E, Montero-Alonso M, Yzusqui M, Clotet B, Videla S, Molto J, Paredes R. A Randomized Trial of Dolutegravir Plus Darunavir/Cobicistat as a Switch Strategy in HIV-1-Infected Patients With Resistance to at Least 2 Antiretroviral Classes. Open Forum Infect Dis. 2023 Oct 31;10(11):ofad542. doi: 10.1093/ofid/ofad542. eCollection 2023 Nov.

  PMID: 38023553 DERIVED

MeSH Terms

Interventions

dolutegravir; Cobicistat

Intervention Hierarchy (Ancestors)

Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Thiazoles; Sulfur Compounds; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: * Experimental group: bitherapy based on DTG (50 mg QD) plus DRV/cobi (800/150 mg QD) * Control group: continuation of their current stable ART.

Study Record Dates

• First Submitted: July 30, 2018
• First Posted: September 25, 2018
• Study Start: November 19, 2018
• Primary Completion: August 10, 2021
• Study Completion: August 10, 2021
• Last Updated: April 1, 2022

Record last verified: 2022-03

Locations

ES (1)