Influence of Cytochrome P2B6 on Efavirenz Dose in HIV-infected Thai Patients

Study Overview
=================
Brief Summary
-----------------
Genetic polymorphisms of cytochrome P450 2B6 (CYP2B6) are associated with lower rate of EFV metabolism and lead to high exposure, as well as a higher risk of neuropsychiatric adverse event especially homozygous variant CYP2B6 *6/*6. This trial was designed to compare the proportion of patients who had undetectable HIV RNA at 24 weeks after ART initiation between patient who did CYP 2B6 guided EFV dose and who did not.

Official Title
-----------------
Influence of Cytochrome P2B6 on Efavirenz Dose in HIV-infected Thai Patients in a Prospective Randomized Controlled Trial: a Proof-of-concept Study

Conditions
-----------------
HIV, Cytochrome P-450 CYP2B6, Efavirenz

Intervention / Treatment
-----------------
* Drug: Efavirenz
* Drug: Efavirenz
* Other: CYP450 2B6


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age ≥18 years old Anti-HIV positive Naïve to antiretroviral drugs Meet the criteria to start ART to Thai National guidelines Sign inform consent Exclusion Criteria: Body mass index (BMI) >25 kg/m² Pregnant women or breastfeeding Received drugs that may have interaction with EFV e.g. rifampicin, fluconazole (400-800 mg), ergot alkaloid, midazolam, triazolam, ritonavir, carbamazepine, phenytoin, phenobarbitone, St John's Wort Having active opportunistic infections e.g. tuberculosis, cryptococcosis, histoplasmosis, penicillosis Hepatic dysfunction as indicated by: Transaminases >5-10 × the upper limit of normal ALP >5-10 × the upper limit of normal Total bilirubin >2.5-5 × the upper limit of normal

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CYP2B6 guided group<br>Patients were assigned to perform CYP2B6 study before ART initiation. If CYP2B6 *6/*6 was found in CYP2B6 *6/*6, the patients will be initiated a low dose of 400 mg of efavirenz (2 tablets of 200 mg) with tenofovir 300 mg and lamivudine 300 mg. | Drug: Efavirenz<br>* There will be adjusted dose of efavirenz in CYP2B6 guide group<br>Drug: Efavirenz<br>* If the patients was diagnosed as hypersensitivity to EFV, they will receive boosted-PI instead.<br>Other: CYP450 2B6<br>* All patients will be monitored drug level which should be in therapeutic level.<br>|
| No Intervention: control group<br>Patients were promptly ART initiation regardless CYP2B6 results. Treatments were efvirenz 600 mg, tenofovir 300 mg and lamivudine 300 mg. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HIV RNA |  | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neuropsychiatric adverse events |  | 24 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
CYP2B6 polymorphism, efavirenz, Thai, HIV-infected patient, pharmacogenomic