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

Phase 2

• Conditions: HIV-1-infection
• Interventions: Drug: Dolutegravir (DTG); Drug: Lamivudine (3TC)

• Registration Number: NCT03539224
• Lead Sponsor: Instituto de Investigación Hospital Universitario La Paz

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.

Study Timeline

• Study Start: 2017-11-02
• Study First Submitted: 2018-04-02
• Study First Submitted QC: 2018-05-25
• Study First Posted: 2018-05-29
• Status Verified: 2020-07
• Last Update Submitted: 2020-07-06
• Last Update Posted: 2020-07-07
• Primary Completion: 2021-05-31
• Study Completion: 2021-07-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 41

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Dolutegravir (DTG) + Lamivudine (3TC)	Lamivudine (3TC)	Eligible subjects will receive one 50 mg tablet of DTG plus 300 mg 3TC tablet orally once daily upto 48 weeks
Dolutegravir (DTG) + Lamivudine (3TC)	Dolutegravir (DTG)	Eligible subjects will receive one 50 mg tablet of DTG plus 300 mg 3TC tablet orally once daily upto 48 weeks

Primary Outcome Measures

Name	Time	Method
Proportion of patients with undetectable viral load (<50 copies / mL) at 48 weeks	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

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

Trial Locations

Locations (2)

Hospital 12 de Octubre; 🇪🇸 Madrid, Spain

Hospital Universitario La Paz; 🇪🇸 Madrid, Spain