Individualized Antiretroviral Therapy (IAT)
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|ClinicalTrials.gov Identifier: NCT03385473|
Recruitment Status : Recruiting
First Posted : December 28, 2017
Last Update Posted : December 28, 2017
The efficacy and safety of antiretroviral therapy and the damage caused by chronic inflammation in the presence of the virus has recently lead to the consideration of initiating antiretroviral therapy earlier than what is required to prevent opportunistic diseases.
Although there may be subtle differences, all recommended antiretroviral combinations for first-line therapy are considered equally effective. Nevertheless, treatment success requires high levels of adherence, which is linked to tolerability and the minimization of adverse effects.
The genes coding the enzymes that are involved in the antiretroviral clearance pathways and the transmembrane transport of drugs are known. These genetic variations can determine the interindividual variations in plasma concentration with the same doses. Both pharmacogenomics (PG) and therapeutic drug monitoring (TDM) may contribute to the individualization of therapy in different chronic conditions through dosing optimization and are associated with a lower risk of concentration-dependent toxicity and potentially greater efficacy. The use of these strategies in the context of antiretroviral therapy is in early stage of development.
Following, our main hypothesis is that PG + TDM dose adjustment of efavirenz or atazanavir in the initial antiretroviral treatment of naive patients with HIV infection is non-inferior in terms of efficacy, has improved safety, and shows a better cost/effectiveness profile than the standard approach with non adjusted doses.
To evaluate our hypothesis we developed this multicenter randomized clinical trial, where patients from 4 clinical sites in Buenos Aires will be included in the protocol and randomized to standard of care (SOC) or pharmacological adaptation (PA) -PA: PG + TDM. For the pharmacogenomics determination, we developed a multiplex approach including main polymorphisms of CYP2B6, CYP2A6, CYP3A4 y ABCB1 for efavirenz; and UGT1A1, ABCB1 and CYP3A4 for atazanavir. Drug plasma levels will be analyzed with ultra-performance liquid chromatography (UPLC).
The main outcomes are to establish the usefulness of PG and TDM in determining the efficacy, safety and cost/effectiveness of a first-line antiretroviral therapy containing either efavirenz or atazanavir in patients with HIV infection who have not received prior antiretroviral therapy.
|Condition or disease||Intervention/treatment||Phase|
|Pharmacogenetics HIV Drug Monitoring||Genetic: Pharmacogenomic index Diagnostic Test: Therapeutic drug monitoring||Not Applicable|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||200 participants|
|Intervention Model:||Sequential Assignment|
|Masking:||None (Open Label)|
|Primary Purpose:||Health Services Research|
|Official Title:||Individualized Antiretroviral Therapy: Impact of Pharmacogenetic and Therapeutic Drug Monitoring in the Safety and Efficacy of First Line Antiretroviral Therapy in Patients With HIV Infection|
|Actual Study Start Date :||October 5, 2017|
|Estimated Primary Completion Date :||December 15, 2019|
|Estimated Study Completion Date :||December 31, 2019|
Active Comparator: Pharmacological Adequation (PA)
Pharmacological adequation based on the Pharmacogenomic Index and therapeutic drug monitoring results.
Genetic: Pharmacogenomic index
All patients will have a blood sample drawn at randomization visits for PG analysis. For patients in the PA arm, the sample will be processed immediately to obtain the PG results and the subsequent index within 10 days. As soon as the results are available, the project team will contact the attending physician to propose the dosing adequation according to the pharmacogenomic index. PG analysis will be performed once for each patient.
Other Name: Diagnostic test
Diagnostic Test: Therapeutic drug monitoring
The patients included in the Pharmacological Adequation arm will have a TDM according to this schedule: day +14 (±3), +28 (±3), and +168 (±3). If there is an abnormal value (out of the therapeutic range), we will proceed to adjust the prescription.
Other Name: TDM
No Intervention: Standard of Care (SOC)
Without pharmacological adequation
- Feasibility of implementation of a multicenter study to analyze pharmacological adequation and therapeutic drug monitoring of efavirenz or atazanavir in the initial antiretroviral treatment of naive patients with HIV infection [ Time Frame: 48 Weeks ]Number of days between obtention of study samples and availability of test results (turnaround time)
- Frequency of adverse events [ Time Frame: 48 Weeks ]Pharmacological Adequation arm of efavirenz or atazanavir in the initial antiretroviral treatment of naive patients with HIV infection will show reduced frequency of adverse events when compared with the Standard Prescription arm.
- Efficacy of antiretroviral treatment [ Time Frame: 48 weeks ]Pharmacological Adequation arm of efavirenz or atazanavir performs equally to the standard of care arm. Viral load at 48 weeks aimed to be non inferior between arms, analyzed through FDA-recommended Snapshot approach.
- Cost/effectiveness compared in both arms [ Time Frame: 48 Weeks ]Pharmacological Adequation arm of efavirenz or atazanavir in the initial antiretroviral treatment of naive patients with HIV infection shows a better cost/effectiveness profile than the standard of care approach. (Direct Cost analysis)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03385473
|Contact: Waldo H Belloso, MD||00 54 11 4959 0200 ext email@example.com|
|Hospital Italiano de Buenos Aires - Infectious Diseases Section||Recruiting|
|Buenos Aires, Caba, Argentina, 1181|
|Contact: Waldo H Belloso, MD 5411 4959 0200 ext 4153 firstname.lastname@example.org|
|Contact: Paula Scibona, MD 5411 4959 0200 ext 4153 email@example.com|
|Principal Investigator: Waldo H Belloso, MD|
|Principal Investigator:||Waldo H Belloso, MD||Hospital Italiano de Buenos Aires|