Resistencia del virus de inmunodeficiencia humano (VIH) a zidovudina (AZT): análisis genotípico en cepas aisladas de pacientes chilenos / Resistance of human immunodeficiency virus (VIH) to zidovudine: genotypic analysis in strains isolated from chilean patients

ABSTRACT

Background: Resistance of HIV to AZT is the result of mutations in the pol gene that codifies the enzyme reverse transcriptase. Aim: To asses the resistance to antiretroviral drugs in Chhilean patients infected with HIV. Material and methods: The presence of mutations was searched in 22 patients infected with HIV. The emergence or persistence of these mutations was studiend in sequential samples of 19 patients. The presence of the mutation that confers resistance to didanosine (ddi) was studied in those subjects exposed to the drug. Polymerase chain reaction techniques were used to analyze mutations in codons 41, 70 and 215 of the pol gene (resistance to AZT) and the mutation in codon 71 (resistance to DDI). Results: On admission, none of the patients without previous exposure to AZT had drug resistance mutations. Seven of 12 patients (58.3 percent) that had received AZT had mutations in codon 215. In two, they were associated to a mutation in codon 41 and in two, to a mutation in codon 70. After a mean follow up of 14 months, 13 of 15 patients (86 percent) that received AZT had viral strains genotypically resistant to the drug. In nine of these, the resistance was associated with disease progression. None of the 10 patients that received DDI had the mutation in codon 74 that confers resistance to the drug. However, in one of these patients, that never receided AZT, virus with a mutation in codon 215 was detected. Conclusions: A high percentage of patients that have received monotheraphy with AZT have genotypic resistance to the drug. This resistance is associated with clinical and immunological derangement in 70 percent of these subjects: