HIV type 1 antiretroviral resistance mutations in subtypes B, C, and F in the City of São Paulo, Brazil.
In Brazil, where three distinct HIV-1 subtypes (B, F, and C) cocirculate, a significant portion of the HIV-infected population has been exposed to antiretroviral drugs. This study analyzes the antiretroviral resistance profiles of HIV-1-infected individuals failing antiretroviral therapy. Genotypic resistance profiles of 2474 patients presenting virologic failure to antiretroviral therapy in the city of São Paulo, Brazil, were generated and analyzed. Resistance mutations to protease inhibitors and nucleoside reverse transcriptase inhibitors were less common in subtype C viruses, whereas nonnucleoside reverse transcriptase inhibitor resistance mutations were less common in subtype F viruses. The thymidine analog mutation pathway known as pathway 1 was more prevalent in subtype B viruses than in subtype C viruses, whereas pathway 2 was more prevalent in subtype C viruses. Selected resistance mutations varied according to subtype for all three classes of antiretrovirals. We describe two distinct pathways of nonnucleoside reverse transcriptase inhibitor resistance (to nevirapine and efavirenz). Although cross-resistance to etravirine should occur more frequently among individuals failing nevirapine treatment, the prevalence of cross-resistance to etravirine, darunavir, and tipranavir was found to be low. We found that increases in the number of resistance mutations will be related to increases in the viral load. Special attention should be given to resistance profiles in non-B subtype viruses. The accumulation of knowledge regarding such profiles in the developing world is desirable.
Munerato
Patricia
P
Infectious Diseases Division, Federal University of São Paulo, São Paulo, Brazil.
Sucupira
Maria Cecilia
MC
Oliveros
Márcia P R
MP
Janini
Luiz Mario
LM
de Souza
Denise Ferreira
DF
Pereira
Anderson Alvarenga
AA
Inocencio
Lilian Amaral
LA
Diaz
Ricardo Sobhie
RS
D000480:Alkynes; D048588:Benzoxazines / Q000627:therapeutic use; D001938:Brazil / Q000453:epidemiology; D015331:Cohort Studies; D003521:Cyclopropanes; D000069454:Darunavir; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics*; D015658:HIV Infections / Q000188:drug therapy / Q000453:epidemiology / Q000821:virology*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D009154:Mutation; D019829:Nevirapine / Q000627:therapeutic use; D009570:Nitriles; D011724:Pyridazines / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D011743:Pyrimidines; D011753:Pyrones / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D013449:Sulfonamides / Q000627:therapeutic use; D017211:Treatment Failure; D019562:Viral Load
D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D017320:HIV Protease Inhibitors; D009570:Nitriles; D011724:Pyridazines; D011725:Pyridines; D011743:Pyrimidines; D011753:Pyrones; D018894:Reverse Transcriptase Inhibitors; D013449:Sulfonamides; C451734:etravirine; D019829:Nevirapine; C098320:efavirenz; D000069454:Darunavir; C107201:tipranavir