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

HIV-1-infection Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03539224
• Other study ID #: ART-PRO
• Secondary ID: 2017-000151-10
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: November 2, 2017
• Est. completion date: July 31, 2021

Study information

• Verified date: July 2020
• Source: Instituto de Investigación Hospital Universitario La Paz
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 41
• Est. completion date: July 31, 2021
• Est. primary completion date: May 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• HIV-1-infection

Intervention

Drug:
• Dolutegravir (DTG)
DTG 50 mg tablet will be orally administered once daily with or without food upto 48 weeks
• 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.

Locations

Country	Name	City	State
Spain	Hospital 12 de Octubre	Madrid
Spain	Hospital Universitario La Paz	Madrid

Sponsors (1)

Lead Sponsor	Collaborator
Instituto de Investigación Hospital Universitario La Paz

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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