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2030-01-01
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LACK OF PRIMARY MUTATIONS ASSOCIATED WITH INTEGRASE INHIBITORS AMONG HIV-1 SUBTYPES B, C, AND F CIRCULATING IN BRAZIL
Brasil
Polimorfismo genético
Inibidores de Integrase de HIV
Subtipos de HIV-1
Mutação de resistência
Brazil
genetic polymorphisms
HIV-1 integrase
HIV-1 subtypes
resistance mutation
Author
Affilliation
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de AIDS e Imunologia Molecular. Rio de Janeiro, RJ. Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de AIDS e Imunologia Molecular. Rio de Janeiro, RJ. Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de AIDS e Imunologia Molecular. Rio de Janeiro, RJ. Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de AIDS e Imunologia Molecular. Rio de Janeiro, RJ. Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de AIDS e Imunologia Molecular. Rio de Janeiro, RJ. Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de AIDS e Imunologia Molecular. Rio de Janeiro, RJ. Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de AIDS e Imunologia Molecular. Rio de Janeiro, RJ. Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de AIDS e Imunologia Molecular. Rio de Janeiro, RJ. Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de AIDS e Imunologia Molecular. Rio de Janeiro, RJ. Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de AIDS e Imunologia Molecular. Rio de Janeiro, RJ. Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de AIDS e Imunologia Molecular. Rio de Janeiro, RJ. Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de AIDS e Imunologia Molecular. Rio de Janeiro, RJ. Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de AIDS e Imunologia Molecular. Rio de Janeiro, RJ. Brasil.
Abstract
Background: Antiretroviral drugs targeting integrase (IN) have
recently been approved for use in combined and salvage therapeutic
interventions.
Objective: To evaluate the presence of natural polymorphisms and
resistance mutations associated with IN inhibitors among HIV-1
subtypes B, C, and F samples obtained from drug-naive individuals
and patients failing highly active antiretroviral therapy in Brazil.
Methods: Proviral DNA was obtained from blood samples of 105
HIV-1–positive drug-naive patients infected by B, C, or F subtypes
and plasma viral RNA from 30 subtype B–infected individuals failing
highly active antiretroviral therapy. The IN region was amplified by
nested polymerase chain reaction and automatically sequenced for
subtype determination. Translated amino acid sequences were
inspected for IN mutations associated with antiretroviral resistance.
Results: Eleven mutations described as conferring in vitro resistance
to IN strand transfer inhibitors were detected among the HIV-1
Brazilian samples. V72I and V201I were considered as polymorphisms.
Major mutations associated with elvitegravir or raltegravir
in vivo resistance (Q148K/H/R, N155H) were not detected.
Conclusions: Although some naturally occurring polymorphisms
were observed, the absence of major resistance mutations for the
current IN inhibitors provides a good rationale for the introduction of
these drugs in Brazil. These results highlight the importance of the
continuous surveillance of IN genetic diversity.
Keywords in Portuguese
Terapia antiretroviralBrasil
Polimorfismo genético
Inibidores de Integrase de HIV
Subtipos de HIV-1
Mutação de resistência
Keywords
antiretroviral treatmentBrazil
genetic polymorphisms
HIV-1 integrase
HIV-1 subtypes
resistance mutation
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