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. 2021 Mar 16:14:335-347.
doi: 10.2147/PGPM.S289471. eCollection 2021.

Association of CYP2B6 Genetic Variation with Efavirenz and Nevirapine Drug Resistance in HIV-1 Patients from Botswana

Monkgomotsi J Maseng  1   2 , Leabaneng Tawe  1   2   3 , Prisca K Thami  2   4 , Kaelo K Seatla  1   2 , Sikhulile Moyo  2   5 , Axel Martinelli  6 , Ishmael Kasvosve  1 , Vladimir Novitsky  2   5 , Max Essex  2   5 , Gianluca Russo  7 , Simani Gaseitsiwe  2   5 , Giacomo M Paganotti  3   8   9
Affiliations

Association of CYP2B6 Genetic Variation with Efavirenz and Nevirapine Drug Resistance in HIV-1 Patients from Botswana

Monkgomotsi J Maseng et al. Pharmgenomics Pers Med. .

Erratum in

Abstract

Purpose: CYP2B6 liver enzyme metabolizes the two non-nucleoside reverse transcriptase inhibitors Efavirenz (EFV) and Nevirapine (NVP) used in the antiretroviral therapy (ART) regimens for HIV-infected individuals. Polymorphisms of the CYP2B6 gene influence drug levels in plasma and possibly virological outcomes. The aim of this study was to explore the potential impact of CYP2B6 genotype and haplotype variation on the risk of developing EFV/NVP drug resistance mutations (DRMs) in HIV-1 patients receiving EFV-/NVP-containing regimens in Botswana.

Patients and methods: Participants were a sub-sample of a larger study (Tshepo study) conducted in Gaborone, Botswana, among HIV-infected individuals taking EFV/NVP containing ART. Study samples were retrieved and assigned to cases (with DRMs) and controls (without DRMs). Four single-nucleotide polymorphisms (SNPs) in the CYP2B6 gene (-82T>C; 516G>T; 785A>G; 983T>C) were genotyped, the haplotypes reconstructed, and the metabolic score assigned. The possible association between drug resistance and several independent factors (baseline characteristics and CYP2B6 genotypes) was assessed by Binary Logistic Regression (BLR) analysis. EFV/NVP resistance status and CYP2B6 haplotypes were also analyzed using Z-test, chi-square and Fisher's exact test statistics.

Results: Two hundred and twenty-seven samples were analysed (40 with DRMs, 187 without DRMs). BLR analysis showed an association between EFV/NVP resistance and CYP2B6 516G allele (OR: 2.26; 95% CI: 1.27-4.01; P=0.005). Moreover, haplotype analysis revealed that the proportion of EFV/NVP-resistant infections was higher among CYP2B6 fast than extensive/slow metabolizers (30.8% vs 16.8%; P=0.035), with the 516G allele more represented in the haplotypes of fast than extensive/slow metabolizers (100.0% vs 53.8%; P<0.001).

Conclusion: We demonstrated that the CYP2B6 516G allele, and even more when combined in fast metabolic haplotypes, is associated with the presence of EFV/NVP resistance, strengthening the need to assess the CYP2B6 genetic profiles in HIV-infected patients in order to improve the virologic outcomes of NNRTI containing ART.

Keywords: ART; CYP2B6 gene; HIV; drug resistance selection; fast metabolizers.

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Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Distribution of CYP2B6-516 genotypes according to NNRTI-resistance status. Chi-square associated P-value is 0.017.
See this image and copyright information in PMC

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References

    1. UNAIDS, 2020. UNAIDS data. 2020. Available from: https://www.unaids.org/sites/default/files/media_asset/2020_aids-data-bo.... Accessed March8, 2021.
    1. Makhema J, Wirth KE, Pretorius Holme M, et al. Universal testing, expanded treatment, and incidence of HIV infection in Botswana. N Engl J Med. 2019;381(3):230–242. doi:10.1056/NEJMoa1812281 - DOI - PMC - PubMed
    1. Essex M, Makhema J, Lockman S. Reaching 90-90-90 in Botswana. Curr Opin HIV AIDS. 2019;14(6):442–448. doi:10.1097/COH.0000000000000580 - DOI - PubMed
    1. WHO, World Health Organization. Antiretroviral therapy coverage estimates by WHO region. 2020. Available from: https://apps.who.int/gho/data/view.main.23300REGION?lang=en. Accessed September15, 2020.
    1. WHO, World Health Organization. HIV drug resistance report 2019. 2019. Available from: https://www.who.int/hiv/pub/drugresistance/hivdr-report-2019/en/. Accessed September15, 2020.

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