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

Development of drug resistance is the inevitable consequence of incomplete suppression of virus plasma levels in HIV-l-infected patients treated with highly active antiretroviral therapy Resistance mutations previously charac terized have been found in a subtype viruses of developed countries. Moreov er, mutation profiles for non-B and more divergent B subtype viruses found in developing countries shall be analyzed together with their ex vivo pheno typing in order to establish an exact correlation between the genotyping da ta and the clinical management counseling for those uncommon virus subtypes . In the present study, we evaluated the mutation profile for individuals i nfected with B subtype and non-a subtype viruses. Viral DNA fragments corre sponding to the RT gene were amplified, sequenced, and subtyped. Phenotypin g analysis for reverse transcriptase nucleoside (NRTI) and nonnucleoside in hibitor susceptibility was performed using the recombinant virus assay tech nology. Brazilian non-B subtypes (subtype F, n = 4, and subtype A, n = 1) i solates 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 nov el result was that some Ri sequences not only revealed the presence of G333 D/E mutations but also correlated to the presence of mutation T3861 that co uld abrogate the M184V-surpassing effect of L210W or L210W plus G333D/E. Th ese findings suggest that Brazilian non-B subtype HIV-1 strains use an iden tical RT drug resistance mutation pattern when compared to a isolates and w ill contribute to the validation of the genotypic and phenotypic tests in t hese predominant worldwide-spread viral variants. (C) 2000 Academic press.