title: Polymorphisms in the HIV-1 gp41 env gene, natural resistance to enfuvirtide (T-20) and pol resistance among pregnant Brazilian women.
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.
authors.affiliation: Tropical Pathology and Public Health Institute, Federal University of Goiás, Goiânia, Goiás, Brazil.
authors.forename: Mônica Nogueira da Guarda
authors.initials: MN
authors.lastname: Reis
authors.forename: Keila Correa
authors.initials: KC
authors.lastname: de Alcântara
authors.forename: Ludimila Paula Vaz
authors.initials: LP
authors.lastname: Cardoso
authors.forename: Mariane Martins Araújo
authors.initials: MM
authors.lastname: Stefani
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology*; D001938:Brazil; D024882:Drug Resistance, Viral; D000077560:Enfuvirtide; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D015700:HIV Envelope Protein gp41 / Q000235:genetics* / Q000494:pharmacology; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010446:Peptide Fragments / Q000494:pharmacology; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000821:virology*; D015995:Prevalence; D017422:Sequence Analysis, DNA; D055815:Young Adult; D054302:pol Gene Products, Human Immunodeficiency Virus / Q000235:genetics*
chemical_list: D019380:Anti-HIV Agents; D015700:HIV Envelope Protein gp41; D010446:Peptide Fragments; C514787:gp41 protein, Human immunodeficiency virus 1; D054302:pol Gene Products, Human Immunodeficiency Virus; D000077560:Enfuvirtide
keywords: Central-West Region Brazil; HIV-1 resistance; enfuvirtide; pregnant women