Lack of primary mutations associated with integrase inhibitors among HIV-1 subtypes B, C, and F circulating in Brazil.
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.
Passaes
Caroline Bittencourt
CB
Laboratory of AIDS and Molecular Immunology, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil.
Guimarães
Monick Lindenmeyer
ML
Fernandez
Saada Lima Chequer
SL
Lorete
Roberta Dos Santos
Rdos S
Teixeira
Sylvia Lopes Maia
SL
Fernandez
José Carlos Couto
JC
Morgado
Mariza Gonçalves
MG
D000595:Amino Acid Sequence; D001938:Brazil; D016384:Consensus Sequence; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification; D024882:Drug Resistance, Viral / Q000235:genetics; D005814:Genes, Viral; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D019427:HIV Integrase / Q000235:genetics*; D019428:HIV Integrase Inhibitors / Q000494:pharmacology*; D015497:HIV-1 / Q000145:classification / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D017386:Sequence Homology, Amino Acid
D004279:DNA, Viral; D019428:HIV Integrase Inhibitors; D019427:HIV Integrase