Genotypic variation of HIV-1 reverse transcriptase and protease: comparative analysis of clade C and clade B.
OBJECTIVE
To compare drug-resistant variants from untreated (naive) and treated patients infected with clade B or C virus.


METHODS
Consecutive samples (165) from patients throughout Israel were analyzed. All those in the treated group were failing highly active antiretroviral therapy.


RESULTS
There were 87 clade B (14 naive) and 78 clade C (20 naive) [corrected] with significant differences in the prevalence of known drug-resistance mutations between the clades: in naive patients in the protease region M36I 7% and 95% (P < 0.0001), K20R 0% and 27% (P = 0.063), A71V 18% and 0% (P = 0.063), M46I 0% and 13%, and V77I 18% and 0% (P = 0.063), respectively, and in the reverse transcriptase region A98G/S 0% and 20% (P = 0.12), respectively. Most clade C viruses also showed significant differences from clade B consensus sequence at additional protease sites: R41K 100%, H69K/Q 85%, L89M 95% and I93L 80% (P < 0.0001). There were also significant differences (P < 0.03 to < 0.0001) in treated patients in clades B and C: in the protease region L10I 40% and 12%, M36I 26% and 95%, L63P 67% and 40%, A71I 38% and 7%, G73I and V77I 18% and 0%, I84V 16% and 3%, and L90M 40% and 12%, respectively; in the reverse transcriptase M41L 41% and 17%, D67N 41% and12%, K70R 30% and 7%, T215Y 48% and 29%, K219Q 21% and 7%, and A98G/S 3% and 24%, respectively.


CONCLUSIONS
Significantly differences between clade B and C viruses may be associated with development of differing resistance patterns during therapy and may affect drug utility in patients infected with clade C.
Grossman
Z
Z
National HIV Reference Center, Central Virology Laboratory, Public Health Laboratories, Ministry of Health, Tel Aviv University Sackler Medical School, Tel Aviv, Israel. lcgross@inter.net.il
Vardinon
N
N
Chemtob
D
D
Alkan
M L
ML
Bentwich
Z
Z
Burke
M
M
Gottesman
G
G
Istomin
V
V
Levi
I
I
Maayan
S
S
Shahar
E
E
Schapiro
J M
JM
D000293:Adolescent; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004352:Drug Resistance, Microbial / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000453:epidemiology / Q000821:virology*; D016333:HIV Protease / Q000235:genetics*; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000145:classification / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011110:Polymorphism, Genetic; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase; D016333:HIV Protease