Genotypic variation of HIV-1 reverse transcriptase and protease: comparative analysis of clade C and clade B

被引:80
作者
Grossman, Z [1 ]
Vardinon, N
Chemtob, D
Alkan, ML
Bentwich, Z
Burke, M
Gottesman, G
Istomin, V
Levi, I
Maayan, S
Shahar, E
Schapiro, JM
机构
[1] Chaim Sheba Med Ctr, Cent Virol Lab, Natl Hemophilia Ctr, IL-52621 Tel Hashomer, Israel
[2] Minist Hlth, Publ Hlth Labs, Cent Virol Lab, Natl HIV Reference Ctr, Tel Aviv, Israel
[3] Tel Aviv Sourasky Med Ctr, Crusaid Kobler Ctr, Clin Immunol Unit, Tel Aviv, Israel
[4] Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel
[5] Minist Hlth, Dept TB & AIDS, Jerusalem, Israel
[6] Soroka Med Ctr, Infect Dis Inst, IL-84101 Beer Sheva, Israel
[7] Ben Gurion Univ Negev, IL-84105 Beer Sheva, Israel
[8] Hebrew Univ Jerusalem, Hadassah Med Sch, Kaplan Hosp, AIDS Ctr, Rehovot, Israel
[9] Hebrew Univ Jerusalem, Hadassah Med Sch, Kaplan Hosp, R Ben Ari Inst Clin Immunol, Rehovot, Israel
[10] Meir Med Ctr, Kefar Sava, Israel
[11] Hillel Jaffe Med Ctr, Hadera, Israel
[12] Tel Hashomer AIDS Ctr, Chaim Sheba Med Ctr, Infect Dis Unit, Jerusalem, Israel
[13] Hadassah Univ Hosp, Dept Clin Microbiol, IL-91120 Jerusalem, Israel
[14] Rambam Med Ctr, Dept Allergy & Immunol, Haifa, Israel
[15] Minist Hlth, Natl HIV Reference Ctr, Publ Hlth Lab, Tel Hashomer, Israel
[16] Minist Hlth, Cent Virol Lab, Publ Hlth Lab, Tel Hashomer, Israel
[17] Haemek Med Ctr, Afula, Israel
[18] Kaplan Med Ctr, Ben Ari Inst Clin Immunol, Rehovot, Israel
[19] Hadassa Univ Hosp, Dept Clin Microbiol, Jerusalem, Israel
[20] Sapir Med Ctr, Kefar Sava, Israel
关键词
HIV-1; genotyping; clade C; resistance; mutations; protease; reverse transcriptase;
D O I
10.1097/00002030-200108170-00001
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 78 clade C (20 naive) and 87 clade B (14 naive) 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% and 12%, K70R 30% and 7%, T215Y 48% and 29%, K219Q 21% and 7%, and A98G/S 3% and 24%, respectively. 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 Lippincott Williams & Wilkins.
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页码:1453 / 1460
页数:8
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