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Individualized Antiretroviral Therapy

CompletedNA

Sponsor: Hospital Italiano de Buenos Aires

Conditions: Pharmacogenetics, HIV, Drug Monitoring

Interventions: Pharmacogenomic index, Therapeutic drug monitoring

Countries: Argentina

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.

Eligibility overview

Sex: ALL

Age: 18 Years to —

Healthy volunteers: No

Study type: INTERVENTIONAL

Eligibility criteria

Inclusion Criteria:

* 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

Exclusion Criteria:

* 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.

Locations (1)

Buenos Aires, Buenos Aires F.D., Argentina