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

Instituto de Investigación Hospital Universitario La Paz

Status and phase: Unknown; Phase 2

Conditions: HIV-1-infection

Treatments: Drug: Dolutegravir (DTG); Drug: Lamivudine (3TC)

Study type: Interventional

Funder types: Other

Identifiers

NCT03539224

ART-PRO

2017-000151-10 (EudraCT Number)

Details and patient eligibility

About

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

Full 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.

Enrollment: 41 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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41 participants in 1 patient group

Dolutegravir (DTG) + Lamivudine (3TC)

Experimental group

Description:

Eligible subjects will receive one 50 mg tablet of DTG plus 300 mg 3TC tablet orally once daily upto 48 weeks

Treatment:

Drug: Lamivudine (3TC)

Drug: Dolutegravir (DTG)