There is one clinical trial.
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.
For atazanavir: Polymorphisms of UGT1A1 (rs8175347), ABCB1 (rs10456542),polymorphisms of the steroid and xenobiotic receptor NR1 2 (rs2472677) TDM for Efavirenz (EFV) and Atazanavir (ATV): UPLC with diode arrangement and mass/mass detection.
Description: Number of days between obtention of study samples and availability of test results (turnaround time)Measure: 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: 48 Weeks
Description: 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.Measure: Frequency of adverse events Time: 48 Weeks
Description: 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.Measure: Efficacy of antiretroviral treatment Time: 48 weeks
Description: 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)Measure: Cost/effectiveness compared in both arms Time: 48 Weeks