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Polymorphisms at CYP enzymes, NR1I2 and NR1I3 in association with virologic response to antiretroviral therapy in Brazilian HIV-positive individuals

The Pharmacogenomics Journal volume 22, pages 33–38 (2022)Cite this article

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Abstract

Virologic failure of antiretroviral therapy (ART) may be explained by single nucleotide polymorphisms (SNPs) in drug absorption and metabolism genes. Here, we characterized the associations between polymorphisms in cytochrome P450 enzymes’ genes CYP2B6 and CYP3A4/A5, nuclear receptor genes NR1I2/3, and initial ART efficacy among 203 HIV-positive individuals from Rio de Janeiro. Association between SNPs and virologic control was evaluated after 6 and 12 months of follow-up using Cox regression models. The SNP rs2307424 (NR1I3) was associated with increased virologic response after 12 months of treatment, while rs1523127 (NR1I2), rs3003596, and rs2502815 (NR1I3) were associated with decreased response. Increased virologic response after 12 months (adjHR = 1.54; p = 0.02) was also observed among carriers of the NR1I3 haplotype rs2502815G-rs3003596A-rs2307424A versus the reference haplotype G-A-G. Our results suggest that NR1I2 and NR1I3 variants are associated with virologic responses to ART among Brazilians.

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Acknowledgements

We are grateful to David W. Haas, MD, from Vanderbilt University, for his thoughtful comments and suggestions. This study was supported by grants from The Brazilian Ministry of Health (TC 235/2012 to C.C.C.), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq; grant number 480753/2013-0 to C.C.C.), Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ; grant number E-26/202.791/2019 to C.C.C.), and Fundação Oswaldo Cruz – Programa INOVA (18801948377 to M.R.A.). C.A.V. is recipient of a graduate fellowship from FAPERJ.

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Author notes

  1. Tailah Bernardo de Almeida

    Present address: Instituto de Estudos do Mar Almirante Paulo Moreira (IEAPM), Marinha do Brasil, Arraial do Cabo, Rio de Janeiro, Brazil

  2. Isabela Espasandin

    Present address: Laboratório de Hanseníase, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil

Authors and Affiliations

  1. Laboratório de Virologia Molecular, Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil

    Camila de Almeida Velozo, Tailah Bernardo de Almeida, Isabela Espasandin, Amilcar Tanuri & Cynthia Chester Cardoso

  2. Hospital Universitário Gaffrée e Guinle, Universidade Federal do Estado do Rio de Janeiro (UNIRIO), Rio de Janeiro, Brazil

    Marcelo Costa Velho Mendes de Azevedo & Jorge Francisco da Cunha Pinto

  3. Laboratório de Biologia Molecular e Proteômica do Sangue – Instituto de Química/LADETEC, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil

    Sheila López & Luciana Pizzatti

  4. Escola Nacional de Saúde Pública Sérgio Arouca, FIOCRUZ, Rio de Janeiro, Brazil

    Sabrina da Silva Santos

  5. Instituto Nacional de Infectologia Evandro Chagas, FIOCRUZ, Rio de Janeiro, Brazil

    Marcelo Ribeiro-Alves

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Contributions

S.S.S. and C.C.C. were responsible for study design. C.A.V., T.B.A., I.E., S.L., and L.P. conducted the experiments. C.A.V., M.R.A., and C.C.C. analyzed the data. M.C.V.M.A. and J.F.C.P. were responsible for subject’s recruitment and clinical follow-up. L.P., A.T., and C.C.C. financed the study. C.A.V., M.R.A., and C.C.C. wrote the manuscript.

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Correspondence to Cynthia Chester Cardoso.

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The authors declare no competing interests.

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This study was approved by the Research Ethics Committee of Hospital Universitário Gaffreé e Guinle, number 94/2011. Written informed consent was obtained from all participants. All procedures were performed in accordance with the Helsinki Declaration.

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de Almeida Velozo, C., de Almeida, T.B., de Azevedo, M.C.V.M. et al. Polymorphisms at CYP enzymes, NR1I2 and NR1I3 in association with virologic response to antiretroviral therapy in Brazilian HIV-positive individuals. Pharmacogenomics J 22, 33–38 (2022). https://doi.org/10.1038/s41397-021-00254-4

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