SNPMiner Trials (Home Page)
Report for Mutation T97A
Developed by Shray Alag, 2020.
SNP Clinical Trial Gene
There are 2 clinical trials
Clinical Trials
1 Efficacy and Safety of a Simplification Strategy Based on Dolutegravir and Darunavir / Cobicistat vs Optimized Treatment in Suppressed HIV-1-infected Patients Carrying Archived Multidrug Resistance Mutations.
The availability of antiretroviral therapy has led to a reduction in morbidity and mortality in patients with chronic HIV infection. The treatment, however, is not free of side effects, has potential interactions with other medications, is expensive and can be complex, especially in those patients who are very experienced and with mutations that give them resistance to multiple drugs. For this reason, the development of simplification strategies that avoid unnecessary exposure to antiretroviral agents remains of great interest. This is a simplification study, in which the investigators try to evaluate that with less medication the investigator can maintain the same virological control of the disease. This would mean a lower burden of medication for patients, facilitating its administration and reducing the number of unwanted side effects. Specifically, the investigators intend to evaluate the treatment with Darunavir / cobicistat plus Dolutegravir as a simplification strategy, since both drugs are taken once a day, have a powerful antiviral activity, even against antiretroviral resistant viruses, and are among the best tolerated (with fewer side effects). The results reported in some observational studies suggest that two-drug therapy (bitherapy) as a simplification strategy could also be safe and effective, however, as far as the investigators know, there are no data and clinical trials that specifically evaluate darunavir / cobicistat plus dolutegravir as a strategy of simplification.
NCT03683524 HIV-1 Infection Drug: Dolutegravir (DTG) plus Darunavir/cobicistat (DRV/cobi). Drug: Current ART
T66I, 74M, E92Q, T97A, F121Y, E138A/K, G140A/S, Y143R/H/C, S147G, Q148H/K/R, N155H AND R263K) in historical genotyping tests. --- T66I --- --- E92Q --- --- T97A ---
Primary Outcomes
Description: HIV-1 RNA < 50 copies/mL using a Time to Loss of Virological Response (TLOVR).
Measure: Plasma HIV-1 RNA < 50 copies/mL at 48 weeks Time: week 48Secondary Outcomes
Description: Percentage of patients developing ART-associated adverse events leading to treatment discontinuation.
Measure: Percentage of patients developing ART-associated adverse events Time: Since baseline to week 48Description: CD4+ cell count changes
Measure: Changes in CD4+ cell count Time: Since baseline to week 48Description: Emergence of new mutations in HIV-1 protease and integrase assessed with a genotyping test (attempted on any post Day 1 sample with HIV-1 RNA ≥ 50 copies/mL).
Measure: Emergence of new mutations in HIV-1 protease and integrase Time: Baseline and in case of virological failure, defined as ≥ 50 copies/mL in 2 consecutive determinations or a single HIV-1 RNA values > 1000 copies/mL. We can observe a virological failure throughout the study (from baseline to week 48)Description: HIV-1 RNA< 50 copies/mL at 24 weeks by TLOVR
Measure: Plasma HIV-1 RNA < 50 copies/mL at 24 weeks Time: Week 24Description: HIV-1 RNA < 50 copies/mL at 24 and 48 weeks using the FDA snapshot analysis (sensitivity analysis).
Measure: Plasma HIV-1 RNA < 50 copies/mL at 24 and 48 weeks Time: Week 24 and 48Description: Description of plasmatic trough levels of DTG and DRV/cobi in the experimental group, and in those participants experiencing virological failure.
Measure: DTG and DRV/cobi plasma concentration Time: Week 4Description: ART prices
Measure: Cost associated with the antirretroviral treatment of the study Time: Since baseline to week 48Description: Prices of clinical controls during the study
Measure: Estimated costs of clinical controls Time: Since baseline to week 48Measure: Genotyping tests cost Time: At virological failure, defined as ≥ 50 copies/mL in 2 consecutive determinations or a single HIV-1 RNA values > 1000 copies/mL. We can observe a virological failure throughout the study (from baseline to week 48)
2 HIV Drug Resistance Profiles Among Individuals Failing Tenofovir/Lamivudine and Dolutegravir First Line Regimen in Brazil
Brazil was the first middle-income country to provide free and universal access to antiretroviral drugs to HIV infected individuals. Since 2014 local guidelines recommend that all HIV infected individuals be started on therapy regardless of CD4 count. Since January 2017, all patients are started on a DTG containing triple regimen. As of November 2018, 170,000 individuals were receiving DTG through the public health system. It is a public health priority to evaluate the risk of virologic failure and the subsequent development of INSTI resistance in these real-life settings. Our preliminary data from Brazil indicated a high virologic failure rate of 8% after 18 months of treatment TL+D. Our central hypothesis is that TDR may be associated and contribute to virologic failure with DTG in clinical practice. To test this central hypothesis, we will identify PLWH failing DTG containing regimens in Brazil. The insights generated with these studies will contribute to a more effective use of second generation INSTI in the future.
NCT04453436 HIV Drug Resistance Drug: Tenofovir Disoproxil
Six (7.1%) additional individuals presented minor IN resistance mutations: L74I/M (2 cases); G140R+G163R; V151A; V151I; T97A; E157Q; and M50I. --- L74I --- --- V151A --- --- V151I --- --- T97A ---
Primary Outcomes
Description: Viral load in patient trated with first line treatment withTenofovir/3TC + Dolutegravir
Measure: HIV RNA Viral Load Time: 24 weeksSecondary Outcomes
Description: HIV reverse transcriptase resistance test in virologic failure patient
Measure: HIV transcriptase resitance mutations Time: 24 weeksDescription: HIV transcriptase resistance test in virologic failure patient
Measure: HIV integrase resitance mutations Time: 24 weeks