Polymorphisms in the HIV-1 gp41 env gene, natural resistance to enfuvirtide (T-20) and pol resistance among pregnant Brazilian women

J Med Virol. 2014 Jan;86(1):8-17. doi: 10.1002/jmv.23738. Epub 2013 Sep 13.

Abstract

The selective pressure of antiretroviral drugs (ARVs) targeting HIV-1 pol can promote drug resistance mutations in other genomic regions, such as env. Drug resistance among women should be monitored to avoid horizontal and mother-to-child transmission. To describe natural resistance to T-20 (enfuvirtide), gp41 env polymorphisms, mutations in pol and HIV-1 subtypes, 124 pregnant women were recruited. For 98 patients, the gp41 env, protease (PR) and reverse transcriptase (RT) fragments were sequenced. The patients were ARV naïve (n = 30), taking mother-to-child transmission prophylaxis (n = 50), or being treated with highly active ARV therapy/HAART (n = 18). The Stanford and IAS/USA databases and other sources were used to analyze PR/RT, gp41 env resistance mutations. The HIV-1 genetic diversity was analyzed by REGA/phylogenetic analyses. The patients' median age was 25 years (range, 16-42), 18.4% had AIDS. The frequency of natural resistance to T-20 (N42D, L44M, and R46M-low-impact mutations) was 6.1% (6/98); 20.4% (20/98) had compensatory mutations in HR2. The prevalence of transmitted drug resistance in the pol was 13.3% (4/30), and the prevalence of secondary drug resistance was 33.3% (6/18). Two patients were infected with multidrug resistant/MDR viruses. The analysis of HIV-1 subtypes (PR/RT/gp41) revealed that 61.2% (60/98) were subtype B, 12.2% (12/98) were subtype C, 4.1% (4/98) were subtype F1, and 22.4% (22/98) were possible recombinants (BF1 = 20.4%; BC = 2%). Natural resistance to T-20 was not associated with pol resistance or previous ARV use. The high rate of secondary resistance, including MDR, indicates that the number of women that may need T-20 salvage therapy may be higher than anticipated.

Keywords: Central-West Region Brazil; HIV-1 resistance; enfuvirtide; pregnant women.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anti-HIV Agents / pharmacology*
  • Brazil
  • Drug Resistance, Viral*
  • Enfuvirtide
  • Female
  • Genetic Variation*
  • Genotype
  • HIV Envelope Protein gp41 / genetics*
  • HIV Envelope Protein gp41 / pharmacology
  • HIV Infections / virology
  • HIV-1 / classification
  • HIV-1 / genetics*
  • HIV-1 / isolation & purification
  • Humans
  • Molecular Sequence Data
  • Mutation, Missense
  • Peptide Fragments / pharmacology
  • Pregnancy
  • Pregnancy Complications, Infectious / virology*
  • Prevalence
  • Sequence Analysis, DNA
  • Young Adult
  • pol Gene Products, Human Immunodeficiency Virus / genetics*

Substances

  • Anti-HIV Agents
  • HIV Envelope Protein gp41
  • Peptide Fragments
  • gp41 protein, Human immunodeficiency virus 1
  • pol Gene Products, Human Immunodeficiency Virus
  • Enfuvirtide

Associated data

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