Clinical trial NCT03539224: Antiretroviral Treatment Guided by Proviral Genotype: Pilot Trial of Proof of Concept.
Official title: Antiretroviral Treatment Guided by Proviral Genotype: Pilot Trial of Proof of Concept.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: HIV-1-infection
Lead sponsor: Instituto de Investigación Hospital Universitario La Paz
Sponsor class: OTHER
First posted: 2018-05-29
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single arm opened with Intervention Type of Drug: Dolutegravir (DTG) and Lamivudina (3TC)
Primary purpose: TREATMENT

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

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.

Eligibility 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.

Primary outcomes:
measure: Proportion of patients with undetectable viral load (<50 copies / mL) at 48 weeks
timeFrame: Week 48
Secondary outcomes:
measure: Proportion of patients with virological failure at 24 weeks
timeFrame: Week 24
measure: Proportion of patients with virological failure at 48 weeks
timeFrame: Week 48
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
timeFrame: Since baseline visits to week 48
measure: Evaluation of the appearance of genotypic resistance mutations (1)
timeFrame: Week 48
Other outcomes:
Locations:
city: Madrid
country: Spain
facility: Hospital 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
Study officials:
References:
citation: 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, Cadinanos 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.