ABCC8 p.Leu210Trp
| Predicted by SNAP2: | A: N (66%), C: N (78%), D: N (57%), E: N (66%), F: N (82%), G: N (53%), H: N (78%), I: N (82%), K: N (61%), M: N (93%), N: N (66%), P: N (78%), Q: N (66%), R: N (66%), S: N (78%), T: N (82%), V: N (82%), W: N (87%), Y: N (87%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: N, K: D, M: N, N: D, P: D, Q: D, R: D, S: D, T: N, V: N, W: D, Y: D, |
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[hide] Prevalence of HIV-1 drug resistance in treated pat... J Acquir Immune Defic Syndr. 2007 Sep 1;46(1):12-8. Costagliola D, Descamps D, Assoumou L, Morand-Joubert L, Marcelin AG, Brodard V, Delaugerre C, Mackiewicz V, Ruffault A, Izopet J, Plantier JC, Tamalet C, Yerly S, Saidi S, Brun-Vezinet F, Masquelier B
Prevalence of HIV-1 drug resistance in treated patients: a French nationwide study.
J Acquir Immune Defic Syndr. 2007 Sep 1;46(1):12-8., [PMID:17514016]
Abstract [show]
BACKGROUND: Surveillance of HIV-1 drug resistance in antiretroviral-treated patients is important from the public health perspective of the spread of resistance and to evaluate the proportion of patients for whom new drugs are needed. METHODS: Patients were consecutively included in 28 centers in France and 1 center in Switzerland if they had a viral load measurement performed in June 2004, with a result >or=1,000 copies/mL. Reverse transcriptase, protease, and gp41 genes were sequenced, and resistance mutations were reported as listed on the Web site ( www.iasusa.org). The genotypic resistance results were interpreted by the Agence Nationale de Recherches sur le SIDA et les Hepatites Virales (ANRS) and Stanford algorithms. RESULTS: The 498 patients included had been exposed to 9 (interquartile ratio [IQR]: 6 to 12) antiretroviral drugs. Patients' viruses harbored 4 nucleoside reverse transcriptase inhibitor (IQR: 1 to 6) and 4 protease inhibitor (PI; IQR: 2 to 8) resistance mutations, whereas 44% had at least 1 nonnucleoside reverse transcriptase inhibitor resistance mutation. The frequency of resistance to at least 1 drug was 88% with the ANRS algorithm and 83% with the Stanford algorithm. The frequencies of complete resistance to 1, 2, and 3 classes of drugs were 37%, 15%, and 4%, respectively, with the ANRS algorithm and 27%, 23%, and 24%, respectively, with the Stanford algorithm. The most important differences between algorithms were for PIs. Using the ANRS algorithm and extrapolation on the whole French database, 19% of all treated patients could contribute to the spread of resistance and 4% had complete resistance to 2 classes of antiretroviral drugs. CONCLUSIONS: The observed patterns of resistance are linked to a long-lasting history of antiretroviral therapy. The frequency of multiresistance can vary according to the interpretation systems.
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54 NRTI resistance mutations selected by thymidine analogues (M41L, D67N, L210W, and T215Y/F) were also present frequently, whereas K70R and K219Q/E were present much less frequently.
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ABCC8 p.Leu210Trp 17514016:54:71
status: NEW[hide] A study of seven rule-based algorithms for the int... J Virol Methods. 2008 Jul;151(1):79-86. Epub 2008 May 6. Poonpiriya V, Sungkanuparph S, Leechanachai P, Pasomsub E, Watitpun C, Chunhakan S, Chantratita W
A study of seven rule-based algorithms for the interpretation of HIV-1 genotypic resistance data in Thailand.
J Virol Methods. 2008 Jul;151(1):79-86. Epub 2008 May 6., [PMID:18462814]
Abstract [show]
Since the free therapy program was started by the Thai government, the number of patients infected by HIV-1 with access to antiretroviral drugs has increased. The selection of effective interpretation algorithms for antiretroviral drug resistance has become even more important for clinical management. In this retrospective study, the level of agreement was evaluated in 721 antiretroviral-therapy failing HIV-1 subjects. Regarding genetic diversity, about 89% was recognized as non-B variants (CRF01_AE). The level of complete concordant interpretation score in all seven algorithms was recognized in non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) (67%), but not in nucleoside reverse transcriptase inhibitors (NRTIs) (52%). Over 10% of the major discordance score with TRUGENE was revealed in didanosine (Agence Nationale de Recherches sur le SIDA[ANRS]; Detroit Medical Centre [DMC]), abacavir (ANRS; Centre Hospitalier de Luxembourg [CHL]), and also with delavirdine, indinavir and amprenavir (Grupo de Aconselhamento Virologico [GAV]). A good to excellent agreement range of kappa scores was detected for most antiretroviral drugs. However, poor agreement with the TRUGENE system (k<0.40) was seen in the ANRS system with didanosine, abacavir and lopinavir; GAV system in indinavir and amprenavir; and DMC system in ritonavir. These might be an option for resource limited countries when selecting the use of a low cost or free algorithm interpretation, which has excellent agreement as the U.S. Food and Drug Administration (FDA)-approved TRUGENE commercial system.
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72 Among 668 (96.7%) other patients infected with non-B HIV-1 variants, the subtype/CRF distribution in decreasing order Table 1 Prevalence of pol gene mutation associated with antiretroviral drug resistance for NRTIs, NNRTIs and PIs in comparison to the total population and two major subtypes (CRF01 AE and B) Mutation RT HIV Total (721) numbers (%) Subtype B (n = 53) numbers (%) CRF01 AE (n = 640) numbers (%) p-Value NRTIs M41L 195(27%) 7(13%) 182(28%) 0.016a E44D 62(9%) 3(6%) 54(8%) 0.61 A62V 22(3%) 4(8%) 17(3%) 0.069 K65R 34(5%) 6(11%) 26(4%) 0.029a D67N 299(42%) 18(34%) 271(42%) 0.25 T69D 36(5%) 3(6%) 30(5%) 0.733 INS69 3(1%) 0(0%) 1(0.2%) 1 K70R 187(26%) 10(19%) 170(27%) 0.256 L74V 38(5%) 5(9%) 32(5%) 0.192 V75I 23(3%) 3(6%) 18(3%) 0.212 F77L 14(2%) 3(6%) 9(1%) 0.057 Y115F 11(2%) 5(9%) 6(1%) 0.001a F116Y 26(4%) 3(6%) 21(3%) 0.419 V118I 138(19%) 8(15%) 124(19%) 0.585 Q151M 36(5%) 4(8%) 30(5%) 0.32 M184V/I 297(41%) 22(42%) 269(42%) 1 L210W 150(21%) 7(13%) 134(21%) 0.215 T215F/Y 283(39%) 15(28%) 257(40%) 0.107 K219Q/E 184(26%) 12(23%) 168(26%) 0.628 NNRTIs L1001 17(2%) 2(4%) 16(3%) 0.641 K103N 161(22%) 10(19%) 145(23%) 0.609 V106A/M 20(3%) 2(4%) 15(2%) 0.378 V108I 61(8%) 5(9%) 54(8%) 0.797 Y181C/I 121(17%) 9(17%) 108(17%) 1 Y188C/L/H 41(6%) 2(4%) 39(6%) 0.761 G190A/S 128(18%) 7(13%) 118(18%) 0.457 P225H 27(4%) 0(0%) 26(4%) 0.251 M230L 10(1%) 1(2%) 9(1%) 0.551 Protease L10F/I/R/V 6(1%) 2(4%) 2(0.3%) 0.031 K20M/R/I/T 3(1%) 1(2%) 0(0%) 0.076 L33F/I/V 4(1%) 2(4%) 1(0.2%) 0.016a M36I/L/V 88(12%) 2(4%) 94(15%) 0.022a M46I/L 39(5%) 0(0%) 32(5%) 0.163 I47V/A 1(1%) 0(0%) 1(0.2%) 1 G48V 17(2%) 2(4%) 13(2%) 0.32 F53L 11(2%) 0(0%) 11(2%) 1 I54VL/M/T/S 37(5%) 4(8%) 30(5%) 0.32 L63P 183(25%) 33(62%) 140(22%) 0a A71V/T 34(5%) 12(23%) 17(3%) 0a G73A/C/S/T 4(1%) 2(4%) 1(0.2%) 0.016a V82A/T/F/S 37(5%) 3(6%) 33(5%) 0.531 I84V 8(1%) 1(2%) 6(1%) 0.428 N88D/S 12(2%) 3(6%) 7(1%) 0.035a L90M 35(5%) 8(15%) 26(4%) 0.003a a Marker indicates the statistically significant difference between subtypes calculated by Fisher`s exact test.
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ABCC8 p.Leu210Trp 18462814:72:948
status: NEW80 The frequency of Multi-NRTI resistance mutations for the thymidine analog or TAMs (M41L, D67N, K70R, L210W, T215F/Y) was detected in about 6 (0.8%) from the overall population, and presented with all five mutations shown; and 159 (22%) gave the highest frequency, containing at least two mutations associated with TAMs (D67N and K70R).
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ABCC8 p.Leu210Trp 18462814:80:101
status: NEW123 In particularly, the frequencies of co-appearance TAM members (M41L, D67N, K70R, L210W, T215F/Y) were commonly prevalent in CRF01 AE when compared to the B subtype.
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ABCC8 p.Leu210Trp 18462814:123:81
status: NEW[hide] Low levels of antiretroviral-resistant HIV infecti... Clin Infect Dis. 2009 May 1;48(9):1318-22. Kouanfack C, Montavon C, Laurent C, Aghokeng A, Kenfack A, Bourgeois A, Koulla-Shiro S, Mpoudi-Ngole E, Peeters M, Delaporte E
Low levels of antiretroviral-resistant HIV infection in a routine clinic in Cameroon that uses the World Health Organization (WHO) public health approach to monitor antiretroviral treatment and adequacy with the WHO recommendation for second-line treatment.
Clin Infect Dis. 2009 May 1;48(9):1318-22., [PMID:19320592]
Abstract [show]
A cross-sectional study, performed at a routine human immunodeficiency virus (HIV)/AIDS clinic in Cameroon that uses the World Health Organization public health approach, showed low rates of virological failure and drug resistance at 12 and 24 months after initiation of antiretroviral therapy. Importantly, the cross-sectional study also showed that the World Health Organization recommendation for second-line treatment would be effective in almost all patients with HIV drug resistance mutations.
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54 Variable Month 12 (n p 249) Month 24 (n p 178) Mutations associated with NRTI resistance f T215Y 1 1 M41L, D67N, L210W, T215Y 1 … M41L, T215FY … 2 M41L L74V, T215Y … 1 D67N, K70R, K219Q … 1 D67N, K70R, K219E … 1 D67N, K70R, T215Y, K219Q … 1 M184V 10 27 Resistance after treatment switcha 2/20 (10.0) 3/16 (18.8) Resistance after treatment interruptionb 0/10 14/24 (58.3) NOTE.
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ABCC8 p.Leu210Trp 19320592:54:113
status: NEW