Z. Grossman et al., Genotypic variation of HIV-1 reverse transcriptase and protease: comparative analysis of clade C and clade B, AIDS, 15(12), 2001, pp. 1453-1460
Objective: To compare drug-resistant variants from untreated (naive) and tr
eated patients infected with clade B or C virus.
Methods: Consecutive samples (165) from patients throughout Israel were ana
lyzed. All those in the treated group were failing highly active antiretrov
iral therapy.
Results: There were 78 clade C (20 naive) and 87 clade B (14 naive) with si
gnificant 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), M
46I 0% and 13%, and V77I 18% and 0% (P = 0.063), respectively, and in the r
everse transcriptase region A98G/S 0% and 20% (P = 0.12), respectively. Mos
t clade C viruses also showed significant differences from clade B consensu
s sequence at additional protease sites: R41K 100%, H69K/Q 85%, L89M 95% an
d 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% and 12%, K70R 30% a
nd 7%, T215Y 48% and 29%, K219Q 21% and 7%, and A98G/S 3% and 24%, respecti
vely.
Conclusion: 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. (C) 2001 Li
ppincott Williams & Wilkins.