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Individualized Antiretroviral Therapy

NCT03385473 · Status: COMPLETED · Phase: NA · Type: INTERVENTIONAL · Enrollment: 190

Last updated 2025-09-09

No results posted yet for this study

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

Interventions

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.

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.

Sponsors & Collaborators

  • Hospital Italiano de Buenos Aires

    lead OTHER

Principal Investigators

  • Waldo H Belloso, MD · Hospital Italiano de Buenos Aires

Study Design

Allocation
RANDOMIZED
Purpose
HEALTH_SERVICES_RESEARCH
Masking
NONE
Model
SEQUENTIAL

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2017-10-05
Primary Completion
2019-12-15
Completion
2019-12-31

Countries

  • Argentina

Study Locations

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Entities

Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT03385473 on ClinicalTrials.gov