Impact of HIV-1 subtype and antiretroviral therapy on protease and reverse transcriptase genotype: results of a global collaboration.
BACKGROUND
The genetic differences among HIV-1 subtypes may be critical to clinical management and drug resistance surveillance as antiretroviral treatment is expanded to regions of the world where diverse non-subtype-B viruses predominate.


RESULTS
To assess the impact of HIV-1 subtype and antiretroviral treatment on the distribution of mutations in protease and reverse transcriptase, a binomial response model using subtype and treatment as explanatory variables was used to analyze a large compiled dataset of non-subtype-B HIV-1 sequences. Non-subtype-B sequences from 3,686 persons with well characterized antiretroviral treatment histories were analyzed in comparison to subtype B sequences from 4,769 persons. The non-subtype-B sequences included 461 with subtype A, 1,185 with C, 331 with D, 245 with F, 293 with G, 513 with CRF01_AE, and 618 with CRF02_AG. Each of the 55 known subtype B drug-resistance mutations occurred in at least one non-B isolate, and 44 (80%) of these mutations were significantly associated with antiretroviral treatment in at least one non-B subtype. Conversely, of 67 mutations found to be associated with antiretroviral therapy in at least one non-B subtype, 61 were also associated with antiretroviral therapy in subtype B isolates.


CONCLUSIONS
Global surveillance and genotypic assessment of drug resistance should focus primarily on the known subtype B drug-resistance mutations.
Kantor
Rami
R
Division of Infectious Disease and Center for AIDS Research, Stanford University, Stanford, California, USA. rkantor@brown.edu
Katzenstein
David A
DA
Efron
Brad
B
Carvalho
Ana Patricia
AP
Wynhoven
Brian
B
Cane
Patricia
P
Clarke
John
J
Sirivichayakul
Sunee
S
Soares
Marcelo A
MA
Snoeck
Joke
J
Pillay
Candice
C
Rudich
Hagit
H
Rodrigues
Rosangela
R
Holguin
Africa
A
Ariyoshi
Koya
K
Bouzas
Maria Belen
MB
Cahn
Pedro
P
Sugiura
Wataru
W
Soriano
Vincent
V
Brigido
Luis F
LF
Grossman
Zehava
Z
Morris
Lynn
L
Vandamme
Anne-Mieke
AM
Tanuri
Amilcar
A
Phanuphak
Praphan
P
Weber
Jonathan N
JN
Pillay
Deenan
D
Harrigan
P Richard
PR
Camacho
Ricardo
R
Schapiro
Jonathan M
JM
Shafer
Robert W
RW
D000595:Amino Acid Sequence; D044966:Anti-Retroviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004252:DNA Mutational Analysis; D024882:Drug Resistance, Viral; D014943:Global Health; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000145:classification / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D008969:Molecular Sequence Data; D010447:Peptide Hydrolases / Q000235:genetics*; D012194:RNA-Directed DNA Polymerase / Q000235:genetics*
D044966:Anti-Retroviral Agents; D012194:RNA-Directed DNA Polymerase; D010447:Peptide Hydrolases