Individualized Antiretroviral Therapy

NCT03385473 | Completed

• 1 other identifier: 1901
• Study Type: interventional
• Target: 190
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pharmacogenetics; HIV; Drug Monitoring

Outcome Measures

Primary Outcomes (1)

• 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

  Number of days between obtention of study samples and availability of test results (turnaround time)

  48 Weeks

Secondary Outcomes (3)

• Frequency of adverse events

  48 Weeks

• Efficacy of antiretroviral treatment

  48 weeks

• Cost/effectiveness compared in both arms

  48 Weeks

Study Arms (2)

Pharmacological Adequation (PA)

ACTIVE COMPARATOR

Pharmacological adequation based on the Pharmacogenomic Index and therapeutic drug monitoring results.

Genetic: Pharmacogenomic index; Diagnostic Test: Therapeutic drug monitoring

Standard of Care (SOC)

NO INTERVENTION

Without pharmacological adequation

Interventions

Pharmacogenomic index GENETIC

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.

Also known as: Diagnostic test

Pharmacological Adequation (PA)

Therapeutic drug monitoring DIAGNOSTIC_TEST

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.

Also known as: TDM

Pharmacological Adequation (PA)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients with diagnosis of chronic HIV infection confirmed by Western blot and / or HIV viral load
• Patients in whom (according to the judgment of the treating physician) antiretroviral therapy should be initiated and this treatment will be a regimen based on Efavirenz or Atazanavir.
• Availability of a baseline genotyping test confirming the absence of primary resistance for the selected drugs.
• Signature of the informed Consent Form

You may not qualify if:

• Patients who remain untreated or those treated with a regimen that does not include efavirenz or atazanavir
• Lack of understanding of the study characteristics or rejection to have samples taken for the pharmacological studies.
• Patients who are not expected to continue their follow-up at the research center for at least one year
• Patients with coinfections or comorbidities that prevent a dose adjustment of efavirenz or atazanavir based on pharmacological parameters.

Sponsors & Collaborators

• Hospital Italiano de Buenos Aires: lead

Study Sites (1)

Hospital Italiano de Buenos Aires - Infectious Diseases Section

Buenos Aires, Buenos Aires F.D., 1181, Argentina

Location

MeSH Terms

Interventions

Drug Monitoring

Intervention Hierarchy (Ancestors)

Monitoring, Physiologic; Diagnostic Techniques and Procedures; Diagnosis

Study Officials

• Waldo H Belloso, MD

  Hospital Italiano de Buenos Aires

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: November 15, 2017
• First Posted: December 28, 2017
• Study Start: October 5, 2017
• Primary Completion: December 15, 2019
• Study Completion: December 31, 2019
• Last Updated: September 9, 2025

Record last verified: 2020-07

Locations

AR (1)