title: Drug-resistant reverse transcriptase genotyping and phenotyping of B and non-B subtypes (F and A) of human immunodeficiency virus type I found in Brazilian patients failing HAART.
abstract: Development of drug resistance is the inevitable consequence of incomplete suppression of virus plasma levels in HIV-1-infected patients treated with highly active antiretroviral therapy. Resistance mutations previously characterized have been found in B subtype viruses of developed countries. Moreover, mutation profiles for non-B and more divergent B subtype viruses found in developing countries shall be analyzed together with their ex vivo phenotyping in order to establish an exact correlation between the genotyping data and the clinical management counseling for those uncommon virus subtypes. In the present study, we evaluated the mutation profile for individuals infected with B subtype and non-B subtype viruses. Viral DNA fragments corresponding to the RT gene were amplified, sequenced, and subtyped. Phenotyping analysis for reverse transcriptase nucleoside (NRTI) and nonnucleoside inhibitor susceptibility was performed using the recombinant virus assay technology. Brazilian non-B subtypes (subtype F, n = 4, and subtype A, n = 1) isolates showed essentially the same B subtype mutation profile, presenting an NRTI drug resistance with similar MIC50% and MIC90% values for all drugs analyzed regardless of their subtypes. A strong cross-resistance phenotype among AZT, 3TC, and abacavir could be seen in all isolates analyzed. A novel result was that some RT sequences not only revealed the presence of G333D/E mutations but also correlated to the presence of mutation T386I that could abrogate the M184V-surpassing effect of L210W or L210W plus G333D/E. These findings suggest that Brazilian non-B subtype HIV-1 strains use an identical RT drug resistance mutation pattern when compared to B isolates and will contribute to the validation of the genotypic and phenotypic tests in these predominant worldwide-spread viral variants.
authors.affiliation: Laboratory of Molecular Virology, Genetic Department, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21944-970, Brazil.
authors.forename: E
authors.initials: E
authors.lastname: Caride
authors.forename: R
authors.initials: R
authors.lastname: Brindeiro
authors.forename: K
authors.initials: K
authors.lastname: Hertogs
authors.forename: B
authors.initials: B
authors.lastname: Larder
authors.forename: P
authors.initials: P
authors.lastname: Dehertogh
authors.forename: E
authors.initials: E
authors.lastname: Machado
authors.forename: C A
authors.initials: CA
authors.lastname: de Sá
authors.forename: W A
authors.initials: WA
authors.lastname: Eyer-Silva
authors.forename: F S
authors.initials: FS
authors.lastname: Sion
authors.forename: L F
authors.initials: LF
authors.lastname: Passioni
authors.forename: J A
authors.initials: JA
authors.lastname: Menezes
authors.forename: A R
authors.initials: AR
authors.lastname: Calazans
authors.forename: A
authors.initials: A
authors.lastname: Tanuri
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001938:Brazil / Q000453:epidemiology; D004252:DNA Mutational Analysis; D004352:Drug Resistance, Microbial; D018432:Drug Resistance, Multiple / Q000235:genetics*; D004359:Drug Therapy, Combination; D005260:Female; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015497:HIV-1 / Q000145:classification* / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D010802:Phylogeny; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D012307:Risk Factors; D016415:Sequence Alignment; D013997:Time Factors; D017211:Treatment Failure
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase