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

Study Overview
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Brief Summary
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Phase IIa, open clinical trial, pilot, single arm and proof of concept.

Detailed Description
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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.

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

Conditions
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HIV-1-infection

Intervention / Treatment
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* Drug: Dolutegravir (DTG)
* Drug: Lamivudine (3TC)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV-1 infected patients. Age> 18 years. Receiving stable antiretroviral treatment for at least 3 months. Current or historical treatment with 3TC or FTC. Willing to change antiretroviral treatment due to intolerance or interest in simplification. 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. Current level of CD4> 350 cells/μL. Naïve to integrase inhibitors. Patient able to understand and give written informed consent. 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. 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: Detection of any of the following mutations in proviral DNA in peripheral blood by conventional sequencing: M184V/I or K65R/E/N. Pregnant, lactating or child-bearing women who do not commit to using an adequate contraceptive method.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Single arm opened with Intervention Type of Drug: Dolutegravir (DTG) and Lamivudina (3TC)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dolutegravir (DTG) + Lamivudine (3TC)<br>Eligible subjects will receive one 50 mg tablet of DTG plus 300 mg 3TC tablet orally once daily upto 48 weeks | Drug: Dolutegravir (DTG)<br>* DTG 50 mg tablet will be orally administered once daily with or without food upto 48 weeks<br>* Other names: Tivicay;Drug: Lamivudine (3TC)<br>* 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.<br>* Other names: Epivir;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with undetectable viral load (<50 copies / mL) at 48 weeks | - 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. | Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with virological failure at 24 weeks | 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. | Week 24 | 
| Proportion of patients with virological failure at 48 weeks | Proportion of patients with virological failure at week 48 according to the FDA snapshot algorithm. | Week 48 | 
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | Incidence of adverse events and discontinuation of treatment due to toxicity or intolerance. | Since baseline visits to week 48 | 
| Evaluation of the appearance of genotypic resistance mutations (1) | Incidence of genotypic resistance mutations in patients with virological failure at week 48. Description and frequency of genotypic resistance mutations. | Week 48 |