HIV-2 protease sequences of subtypes A and B harbor multiple mutations associated with protease inhibitor resistance in HIV-1.
BACKGROUND
HIV-1 protease inhibitors (PI) have been used for treating HIV-2-infected persons but little is known about amino acid mutations associated with PI resistance in HIV-2 and whether they are similar to those seen in HIV-1.


OBJECTIVE
To determine the frequency of HIV-1 PI resistance-associated mutations in PI-naive HIV-2-infected individuals.


METHODS
Using PCR, protease genes were amplified from 76 individuals, directly sequenced, phylogenetically subtyped, and translated into amino acids to analyze PI-associated major and minor mutations.


RESULTS
Of the 76 HIV-2 sequences, 68% belonged to subtype A and 32% to subtype B. All sequences contained at least four codon changes giving substitutions at 10, 30, 32, 36, 46, 47, 71 or 77. The frequency of these mutations was similar in subtype A and B viruses. Two major resistance-conferring mutations, 30N and 46I, were identified in one (1%) and 68 (89%) specimens, respectively. Minor mutations 10V/I, 32I, 36I, 47V, and 71V were predominant (89%-100%), followed by the rare mutation 77I (1%). Of the 76 strains, 89% harbored multiple PI resistance-associated substitutions comprising both the major 46I and minor mutations: 10V/I, 32I, 36I, 46I, 47V, 71V (76%); 10V, 32I, 36I, 46I, 47V (9%); and 10V, 32I, 36I, 46I, 47V 71V, 77I (1.3%), 10V, 32I, 46I, 47V, 71V (1.3%), and 10V, 30N, 32I, 36I, 46I, 47V, 71V (1.3%). The remaining 11% of the sequences had patterns with only minor mutations: 10V, 32I, 36I, 47V, 71V (9%) and 10V, 32I, 36I, 47V (1.3%).


CONCLUSIONS
The high frequency of multiple PI-associated substitutions represent natural polymorphisms occurring in HIV-2 strains of subtypes A and B. Phenotypic and clinical studies are needed to determine the relevance of these substitutions.
Pieniazek
Danuta
D
HIV and Retrovirology Branch and the Office of the Director, Division of AIDS, STD, and TB Laboratory Research, National Center for Infectious Diseases, Atlanta, Georgia, USA.
Rayfield
Mark
M
Hu
Dale J
DJ
Nkengasong
John N
JN
Soriano
Vincent
V
Heneine
Walid
W
Zeh
Clement
C
Agwale
Simon M
SM
Wambebe
Charles
C
Odama
Liliana
L
Wiktor
Stefan Z
SZ
D000595:Amino Acid Sequence; D016282:Aspartic Acid Endopeptidases / Q000235:genetics*; D004279:DNA, Viral / Q000235:genetics; D024882:Drug Resistance, Viral / Q000235:genetics*; D014644:Genetic Variation; D015658:HIV Infections / Q000821:virology*; D016333:HIV Protease; D017320:HIV Protease Inhibitors / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D015498:HIV-2 / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010802:Phylogeny
D004279:DNA, Viral; D017320:HIV Protease Inhibitors; D016282:Aspartic Acid Endopeptidases; D016333:HIV Protease; C065184:p16 protease, Human immunodeficiency virus 2