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. 2021 Jul 24:14:915-926.
doi: 10.2147/PGPM.S306358. eCollection 2021.

Influence of SULT1A1*2 Polymorphism on Plasma Efavirenz Concentration in Thai HIV-1 Patients

Monpat Chamnanphon #  1   2 , Rattanaporn Sukprasong #  3   4 , Andrea Gaedigk  5   6 , Weerawat Manosuthi  7 , Pajaree Chariyavilaskul  2 , Supeecha Wittayalertpanya  2 , Napatrupron Koomdee  3   4 , Thawinee Jantararoungtong  3   4 , Apichaya Puangpetch  3   4 , Chonlaphat Sukasem  3   4
Affiliations

Influence of SULT1A1*2 Polymorphism on Plasma Efavirenz Concentration in Thai HIV-1 Patients

Monpat Chamnanphon et al. Pharmgenomics Pers Med. .

Abstract

Purpose: Plasma efavirenz (EFV) concentrations within therapeutic levels are essential to successfully treat patients suffering from human immunodeficiency virus (HIV) type 1. In addition to the drug-metabolizing enzyme CYP2B6, other phase II drug-metabolizing enzymes and transporters may have an important role in the pharmacokinetics of EFV. Thus, the influence of phase II drug-metabolizing enzymes and drug transporters on plasma EFV levels was investigated in Thai HIV patients receiving EFV.

Patients and methods: Genotyping was performed by TaqMan® real-time PCR in 149 HIV-infected Thai adults, and plasma efavirenz concentration was measured by a validated high-performance liquid chromatography in 12 hours after dosing steady-state plasma samples at week 12 and 24.

Results: Patients with three or more copies of SULT1A1 had significantly lower median plasma EFV concentrations than those carrying two copies at week 12 (p=0.046) and SULT1A1*2 (c.638G>A) carriers had significantly lower median plasma EFV concentrations compared to those not carrying the variant at week 24 (p=0.048). However, no significant association was found after adjusting for CYP2B6 genotype.

Conclusion: Genetic variation in a combination of SULT1A1*2 and SULT1A1 copy number may contribute to variability in EFV metabolism and thereby may impact drug response. The influence of a combination between the SULT1A1 and CYP2B6 genotype on EFV pharmacokinetics should be further investigated in a larger study population.

Keywords: HIV-1; Thai; efavirenz; phase II drug-metabolizing enzymes; transporter genes.

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Conflict of interest statement

The authors reported no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Influence of SULT1A1*2 (c.638G>A) on median plasma efavirenz (EFV) concentrations at week 12 and 24. Dash lines represent the therapeutic window for EFV (1–4 mg/L). (A) Median plasma EFV concentrations compared between groups (p=0.638) at week 12. (B) Median plasma EFV concentrations were significantly lower in heterozygous patients (638G/A; 2.18 mg/L, IQR 1.44–2.60, p=0.048) compared to those not carrying the variant (638G/G; 2.33 mg/L, IQR 1.57–4.21).
Figure 2
Figure 2
Influence of SULT1A1 copy number variation on median plasma efavirenz (EFV) concentrations at week 12. Dash lines represent the therapeutic window for EFV (1–4 mg/L). A comparison of SULT1A1 copy number (CN) and median plasma EFV concentration at week 12. Median plasma EFV concentrations were significantly lower in patients with CN≥3 (p=0.046), CN=3 (p=0.019), and CN=3+4 (p=0.015) compared to those carrying CN=2.
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