HIV-1-infection
Conditions
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.
Interventions
DTG 50 mg tablet will be orally administered once daily with or without food upto 48 weeks
DRUGLamivudine (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.
Sponsors
Instituto de Investigación Hospital Universitario La Paz
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single arm opened with Intervention Type of Drug: Dolutegravir (DTG) and Lamivudina (3TC)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
Countries
Spain
Outcome results
None listed