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

Mahidol University

Status and phase: Unknown; Phase 1

Conditions: Efavirenz; HIV; Cytochrome P-450 CYP2B6

Treatments: Drug: Efavirenz; Other: CYP450 2B6

Study type: Interventional

Funder types: Other

Identifiers

NCT02421289

ID 05-56-13

Details and patient eligibility

About

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.

Enrollment: 190 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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190 participants in 2 patient groups

CYP2B6 guided group

Experimental group

Description:

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.

Treatment:

Drug: Efavirenz

Drug: Efavirenz

Other: CYP450 2B6

control group

No Intervention group

Description:

Patients were promptly ART initiation regardless CYP2B6 results. Treatments were efvirenz 600 mg, tenofovir 300 mg and lamivudine 300 mg.