Antiretroviral Treatment Guided by Proviral Genotype: Pilot Trial of Proof of Concept.

• ClinicalTrials.gov Identifier: NCT03539224
• Recruitment Status: Active, not recruiting
• First Posted: May 29, 2018
• Last Update Posted: July 7, 2020
• Sponsor: Instituto de Investigación Hospital Universitario La Paz
• Information provided by (Responsible Party): Instituto de Investigación Hospital Universitario La Paz

Study Description

Brief Summary:

Phase IIa, open clinical trial, pilot, single arm and proof of concept.

Condition or disease	Intervention/treatment	Phase
HIV-1-infection	Drug: Dolutegravir (DTG); Drug: Lamivudine (3TC)	Phase 2

Detailed Description:

Proof of concept trial evaluating safety and efficacy of treatment with Dolutegravir (DTG) + lamivudine (3TC) once daily in suppressed participants with history of previous treatment with 3TC or emtricitabine (FTC). Half of the participants will have history of failure with 3TC or FTC and M184V/I or K65R/E/N mutations in previous plasma genotypes, although to be eligible these mutations cannot be detectable at study entry in proviral DNA.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 41 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Single arm opened with Intervention Type of Drug: Dolutegravir (DTG) and Lamivudina (3TC)
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Antiretroviral Treatment Guided by Proviral Genotype: Pilot Trial of Proof of Concept.
• Actual Study Start Date: November 2, 2017
• Estimated Primary Completion Date: May 31, 2021
• Estimated Study Completion Date: July 31, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Dolutegravir (DTG) + Lamivudine (3TC); Eligible subjects will receive one 50 mg tablet of DTG plus 300 mg 3TC tablet orally once daily upto 48 weeks	Drug: Dolutegravir (DTG); DTG 50 mg tablet will be orally administered once daily with or without food upto 48 weeks; Other Name: Tivicay; Drug: Lamivudine (3TC); Lamivudine will be dispensed as 300 mg white, diamond shaped, scored, film coated tablets. It will be orally administered once daily with or without food upto 48 weeks.; Other Name: Epivir

Outcome Measures

Primary Outcome Measures :

1. Proportion of patients with undetectable viral load (<50 copies / mL) at 48 weeks [ Time Frame: Week 48 ]
   - Efficacy: Proportion of patients with undetectable viral load (<50 copies / mL) at 48 weeks of follow-up, according to the FDA snapshot algorithm in the population "by intention to treat-exposed". The intention-to-treat population includes all patients who have received at least one dose of DTG and 3TC.

Secondary Outcome Measures :

1. Proportion of patients with virological failure at 24 weeks [ Time Frame: Week 24 ]
   Proportion of patients with viral load <50 copies/ml at week 24, according to the FDA snapshot algorithm in the population "by intention to treat-exposed".
2. Proportion of patients with virological failure at 48 weeks [ Time Frame: Week 48 ]
   Proportion of patients with virological failure at week 48 according to the FDA snapshot algorithm.
3. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: Since baseline visits to week 48 ]
   Incidence of adverse events and discontinuation of treatment due to toxicity or intolerance.
4. Evaluation of the appearance of genotypic resistance mutations (1) [ Time Frame: Week 48 ]
   Incidence of genotypic resistance mutations in patients with virological failure at week 48. Description and frequency of genotypic resistance mutations.

Eligibility Criteria

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

Criteria

Inclusion Criteria:

1. HIV-1 infected patients.
2. Age> 18 years.
3. Receiving stable antiretroviral treatment for at least 3 months.
4. Current or historical treatment with 3TC or FTC.
5. Willing to change antiretroviral treatment due to intolerance or interest in simplification.
6. Undetectable viral load (<50 cop/mL) for at least 1 year prior to the inclusion. A single viral load >50cop/ml (≤500 copies/ml) is allowed before the three months prior to inclusion in the study, preceded and followed by an undetectable determination.
7. Current level of CD4> 350 cells/μL.
8. Naïve to integrase inhibitors.
9. Patient able to understand and give written informed consent.
10. For those included in group 1 (20 patients): No previous history of virological failure with ART regimen that included 3TC or FTC or previous virological failure had a population genotype without M184V/I or K65R/E/N mutations.
11. For those included in group 2 (20 patients): previous history of virological failure with ART regimen that included 3TC or FTC and historical genotype with M184V/I or K65R/E/N mutations.

Exclusion Criteria:

1. Detection of any of the following mutations in proviral DNA in peripheral blood by conventional sequencing: M184V/I or K65R/E/N.
2. Pregnant, lactating or child-bearing women who do not commit to using an adequate contraceptive method.

Contacts and Locations

Locations

Spain

Hospital 12 de Octubre

Madrid, Spain, 28041

Hospital Universitario La Paz

Madrid, Spain, 28046

Sponsors and Collaborators

Instituto de Investigación Hospital Universitario La Paz

More Information

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

De Miguel R, Rial-Crestelo D, Dominguez-Dominguez L, Montejano R, Esteban-Cantos A, Aranguren-Rivas P, Stella-Ascariz N, Bisbal O, Bermejo-Plaza L, Garcia-Alvarez M, Alejos B, Hernando A, Santacreu-Guerrero M, Cadiñanos J, Mayoral M, Castro JM, Moreno V, Martin-Carbonero L, Delgado R, Rubio R, Pulido F, Arribas JR; ART-PRO, PI16/00837-PI16/00678 study group. Dolutegravir plus lamivudine for maintenance of HIV viral suppression in adults with and without historical resistance to lamivudine: 48-week results of a non-randomized, pilot clinical trial (ART-PRO). EBioMedicine. 2020 May;55:102779. doi: 10.1016/j.ebiom.2020.102779. Epub 2020 May 11.

• Responsible Party: Instituto de Investigación Hospital Universitario La Paz
• ClinicalTrials.gov Identifier: NCT03539224
• Other Study ID Numbers: ART-PRO; 2017-000151-10 ( EudraCT Number )
• First Posted: May 29, 2018
• Last Update Posted: July 7, 2020
• Last Verified: July 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Lamivudine; Dolutegravir; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anti-Retroviral Agents; Antiviral Agents; Anti-Infective Agents; Anti-HIV Agents; HIV Integrase Inhibitors; Integrase Inhibitors