The CYP2B6 G516T polymorphism influences CD4+ T-cell counts in HIV-positive patients receiving antiretroviral therapy in an ethnically diverse region of the Amazon

Int J Infect Dis. 2017 Feb:55:4-10. doi: 10.1016/j.ijid.2016.12.002. Epub 2016 Dec 9.

Abstract

Objectives: Cytochrome P450 (CYP) enzyme polymorphisms seem to significantly influence the variability of the responses to certain antiretroviral drugs and their toxicity levels. The objective of this study was to evaluate the influence of the CYP2B6 G516T polymorphism on hepatic, renal, immunological, and viral marker changes in HIV-1-positive patients receiving treatment in an ethnically diverse region of the Amazon.

Methods: CYP2B6 G516T genotyping was performed by real-time PCR (RT-PCR) in samples from 185 patients. Urea, creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT), CD4+/CD8+ T-cell counts, and HIV-1 plasma viral load were measured.

Results: The polymorphic CYP2B6 G516T allele frequency was 0.36, which is different from the frequencies in other ethnic groups. The polymorphic genotype was associated with changes in the urea and ALT levels, although the median values were within the normal range. The TT genotype was also associated with significantly lower CD4+ T-cell counts in patients using efavirenz.

Conclusions: The CYP2B6 G516T polymorphism seems to affect the response to efavirenz treatment by reducing CD4+ T-cell counts in patients with a high degree of miscegenation who use this antiretroviral agent.

Keywords: Antiretroviral drugs; CYP2B6; HIV-1; Miscegenation; Treatment response.

MeSH terms

  • Adult
  • Alkynes
  • Anti-HIV Agents / therapeutic use*
  • Benzoxazines / therapeutic use
  • Brazil
  • CD4 Lymphocyte Count*
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / drug effects
  • Cyclopropanes
  • Cytochrome P-450 CYP2B6 / genetics*
  • Ethnicity / genetics*
  • Female
  • Genotype
  • HIV Infections / drug therapy*
  • HIV Infections / genetics
  • HIV Infections / immunology*
  • HIV Infections / virology
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Young Adult

Substances

  • Alkynes
  • Anti-HIV Agents
  • Benzoxazines
  • Cyclopropanes
  • Cytochrome P-450 CYP2B6
  • efavirenz