ライフサイエンスコーパス: AZT

1 AZT (3'-azido-3'-deoxythymidine) resistance involves the

2 AZT 5'-alpha-R(P)-borano-beta,gamma-(difluoromethylene)t

3 AZT also enhanced the activity of paclitaxel in mice bea

4 AZT and IFN-alpha mediated apoptosis in PEL was blocked

5 AZT monophosphate, the principal intracellular metabolit

6 AZT resistance is due to enhanced excision of AZT 5'-mon

7 AZT resistance mutations were detected in 2 (8.3%) neona

8 AZT strongly stimulated the "template-switch" class of m

9 AZT treatment resulted in the production of fewer highly

10 AZT(R) RT did not excise terminal nucleotides more frequ

11 AZT, which does not cause a peripheral neuropathy in pat

12 AZT- and IFN-alpha-mediated apoptosis was blocked by exp

13 AZT-associated mutations were detected in 17.3% of pregn

14 AZT-MP and substantial amounts of either phosphoramidate

15 V-1 CRF02_AG, 8 treatment-naive and 4 on 3TC-AZT-NVP] showed 3 to 4 mutations in the Gag P2/NC CS: S3

16 AART drugs (indinavir, lamivudine, abacavir, AZT, and ddI) and the 3-plex significantly also impaired

17 at viruses with D67N and/or K219Q/E acquired AZT resistance mutations more rapidly than WT viruses (3

18 excision-based resistance mechanism against AZT, HIV-2 RT can use only the exclusion mechanism.

19 readily adopts an exclusion pathway against AZT triphosphate (AZTTP), while HIV-1 RT is better able

20 ique mechanism increases selectivity against AZT incorporation by allowing reversal of the reaction a

21 Outcomes for wild-type (WT) RT and an AZT-resistant (AZT(R)) RT containing a thymidine analog

22 specificity of the excision reaction for an AZT-terminated primer is not due to the mutations that c

23 enzyme's affinity to bind the same T/P in an AZT-MP excision competent mode.

24 nvolving the azido group cause the end of an AZT 5'-monophosphate-terminated primer to preferentially

25 V-2 RT excision competent did not produce an AZT-resistant RT but instead yielded RTs that were less

26 ld resistance of the triazole analogue to an AZT-resistant HIV variant (9-fold compared to 56-fold wi

27 uent ART regimens were TDF/3TC/EFV (39%) and AZT/3TC/NVP (34%); 49% of pregnancies had prenatal TDF e

28 (-)2',3'-dideoxy-3'-thiacytidine (3TC), and AZT-resistant HIV-1 reverse transcriptase (RT) can incre

29 onavir, indinavir, lamivudine, abacavir, and AZT) significantly decreased endothelial nitric oxide sy

30 and K219Q) on in vitro RNase H activity and AZT monophosphate (AZTMP) excision.

31 more effective excision of (-)3TC, CBV, and AZT may contribute to lower toxicity.

32 ndicate that resistance pathways for d4T and AZT may not be identical.

33 similar for patients exposed to TDF, d4T and AZT, suggesting all regimens were equally effective.

34 reduces susceptibility to NVP, EFV, ETV, and AZT.

35 s that are resistant to tenofovir (K65R) and AZT (Q151M), are also resistant to the respective drugs,

36 incorporation were comparable with PMPA and AZT.

37 Furthermore, both ritonavir and AZT substantially activated ERK2 in HPAECs.

38 ERK1/2 also partially blocked ritonavir- and AZT-induced down-regulation of eNOS and vasomotor dysfun

39 biochemical difference between wild-type and AZT resistant HIV-1 RT manifested itself during ATP-medi

40 e majority of tested mismatches, both WT and AZT(R) RTs extended mismatches in more than 90% of provi

41 ediate resolution repertoires between WT and AZT(R) RTs on one mismatched replication intermediate.

42 As AZT and ddC are known to cause mitochondrial dysfunction

43 aB-betagammaCF(2)TP) (6d-I), is as potent as AZT triphosphate with a K(i)() value of 9.5 nM and at le

44 o the 3'-azidopyrimidine nucleosides (AZddC, AZT, and AZddU) but not to the 3'-azidopurine nucleoside

45 ,3'-ddC (AZddC), 3'-azido-2',3'-ddG (AZddG), AZT, and 3'-azido-2',3'-ddU (AZddU).

46 ide scaffold derived from 3'-azidothymidine (AZT) consistently and selectively inhibiting WNV and DEN

47 3'-Azidothymidine (AZT) was the first approved antiviral for the treatment

48 tions that do not include 3'-azidothymidine (AZT).

49 e antiviral thymidine analog azidothymidine (AZT) is used to treat several virus-associated human can

50 rferon alpha (IFN-alpha) and azidothymidine (AZT) induces apoptosis in PEL cell lines.

51 ibitors hydroxyurea (HU) and azidothymidine (AZT) was suppressed by alleles of dnaA that reduce the e

52 AIDS pharmaceuticals such as azidothymidine (AZT), anti-malarial compounds and novel vaccines saving

53 s is with the antiviral drug azidothymidine (AZT).

54 >> (+)3TC >> (-)3TC > PMPA > azidothymidine (AZT) >> Carbovir (CBV).

55 We have found that Azidothymidine (AZT) alone induces apoptosis in Epstein Barr Virus (EBV)

56 vity of radA recG mutants to azidothymidine (AZT) can be rescued by blocking recombination with recA

57 tients receiving zidovudine (azidothymidine [AZT], -3.64 g/dL vs. no AZT, -2.08 g/dL), and patients r

58 mulated in cells increases as the aztreonam (AZT) concentration increases and as incubation time incr

59 site for phosphorolytic excision of AZTMP by AZT-resistant (AZT(R)) RT.

60 confer increased phosphorolytic excision by AZT(R) RT for all 3'-azido-ddNMP analogs.

61 at microhomologies were enhanced modestly by AZT.

62 mediated by K65R, a mutation not selected by AZT.

63 H domains of RT can be selected in vitro by AZT and confer greater AZT resistance and cross-resistan

64 However, unlike the classic AZT resistance mutations (M41L/D67N/K70R/T215Y or F/K219

65 ype RT or a mutant RT carrying the classical AZT resistance mutations.

66 ediated excision produces the novel compound AZT-(5')-tetraphospho-(5')-adenosine (AZTp4A).

67 The most active compound, AZT 5'-alpha-R(p)()-borano-beta,gamma-(difluoromethylene

68 defined the mechanism by which Q509L confers AZT resistance by performing in-depth biochemical analys

69 R with antiretroviral therapies that contain AZT, and its more frequent emergence with combinations t

70 rinucleoside glutamate derivative containing AZT, FLT, and 3TC (34, EC(50) = 0.9-1.4 muM) exhibited h

71 In contrast, AZT did not enhance the paclitaxel activity in the telom

72 ficient excision of dideoxynucleotides, D4T, AZT, and CBV from DNA predicts persistence in vivo follo

73 t D67N/K70R/M73K RT showed 10-fold decreased AZT susceptibility and increased rescue efficiency on AZ

74 to the inhibitor 3'-azido-3'deoxythymidine (AZT).

75 iptase inhibitor 3'-azido-3'-deoxythymidine (AZT) and by mutation of the integrase gene in the packag

76 te monoesters of 3'-azido-3'-deoxythymidine (AZT) bearing aliphatic amino acid methyl esters (3a, 3c,

77 ed resistance to 3'-azido-3'-deoxythymidine (AZT) from 11-fold to as much as 536-fold over wild-type

78 ng resistance to 3'-azido-3'-deoxythymidine (AZT) in Escherichia coli.

79 ance of HIV-1 to 3'-azido-3'-deoxythymidine (AZT) involves phosphorolytic excision of chain-terminati

80 1 resistance to 3'-azido-3'-deoxythymidine (AZT) involves reverse transcriptase (RT)-catalyzed phosp

81 se (RT) increase 3'-azido-3'-deoxythymidine (AZT) resistance in the context of thymidine analog mutat

82 icantly increase 3'-azido-3'-deoxythymidine (AZT) resistance up to 536 times over wild-type (WT) RT i

83 e to zidovudine (3'-azido-3'-deoxythymidine (AZT)) and other NRTIs is conferred by mutations affectin

84 have shown that 3'-azido-3'-deoxythymidine (AZT), (-)2',3'-dideoxy-3'-thiacytidine (3TC), and AZT-re

85 erase inhibitor, 3'-azido-3'-deoxythymidine (AZT), at a concentration that produced little or no cell

86 pronounced with 3'-azido-3'-deoxythymidine (AZT), in which 78% of the reaction product was AZT dipho

87 RT), such as the 3'-azido-3'-deoxythymidine (AZT)-resistant variant AZT-R (M41L/D67N/K70R/T215Y/K219Q

88 igen produced by 3'-azido-3'-deoxythymidine (AZT)-sensitive HIV-1 isolates, A012 and A018, in phytohe

89 t HIV infection, 3'-azido-3'-deoxythymidine (AZT).

90 eoside inhibitor 3'-azido-3'-deoxythymidine (AZT).

91 s to zidovudine (3'-azido-3'-deoxythymidine; AZT).

92 kinetics of 3'-azido-2',3'-dideoxythymidine (AZT) incorporation exhibit an increase in amplitude and

93 (RT) increase 3'-azido-3'-dideoxythymidine (AZT) resistance.

94 cil (FMAU), 3'-azido-2',3'-dideoxythymidine (AZT), and 2',3'-didehydro-2',3'-dideoxythymidine (D4T) a

95 in-2-one, 2-pyridone, pyrimidine-2,4-diones (AZT derivatives), or inosines to the electron-deficient

96 mplete response after therapy with high-dose AZT and GCV in the absence of WBRT, and remains in remis

97 At sublethal doses, AZT has no significant effect on frame shifts and most b

98 velopment of resistance to the anti-HIV drug AZT.

99 Furthermore, the anti-HIV-1 drugs AZT, tenofovir, and raltegravir may be useful for treatm

100 dually resistant RT and several drugs (i.e., AZT, 3TC, hydroxyurea, and thymidine) and led to increas

101 atal transmission and the presence of either AZT or nucleoside reverse-transcriptase inhibitor resist

102 Here, we report that enduring AZT treatment of T-cell leukemia virus I-infected cells,

103 primer grip region can significantly enhance AZT resistance and support the hypothesis that mutations

104 An A400T substitution in subtype B enhanced AZT resistance, increased AZTMP excision on both RNA and

105 is that connection domain mutations enhanced AZT resistance by influencing the RNase H primer grip, w

106 HIV-2 RT has a much lower ability to excise AZT monophosphate (AZTMP) than does WT HIV-1 RT and sugg

107 ent emergence with combinations that exclude AZT.

108 We report herein the first AZT-derived 1,2,3-triazoles with submicromolar potencies

109 omain, that together conferred up to 90-fold AZT resistance.

110 The excision reaction is specific for AZT because HIV-1 RT, which can form a closed complex wi

111 ision reaction to be relatively specific for AZT?

112 an excellent chain-terminating substrate for AZT-resistant RT-catalyzed DNA synthesis, better than AZ

113 red to 17.9 for d4T and 8.5 per 100 P/Ys for AZT.

114 icity of the excision phenotype arising from AZT resistance mutations.

115 boronation and subsequent hydrolysis to give AZT 5'-alpha-borano-beta,gamma-bridge-modified triphosph

116 selected in vitro by AZT and confer greater AZT resistance and cross-resistance to nucleoside RT inh

117 (+)3TC approximately equal to (-)3TC > CBV > AZT > PMPA approximately equal to d4T >> ddA (ddI) >> dd

118 B2(WT) in the presence of either low or high AZT concentrations, likely reflecting low-level resistan

119 _AE containing TAMs exhibited 64-fold higher AZT resistance relative to wild-type B, whereas AZT resi

120 d by T215F, resulting in a large increase in AZT resistance ( approximately 16,000-fold).

121 iated strongly with the observed increase in AZT resistance; several of these mutations also decrease

122 The roles of A371V and Q509L in AZT resistance were confirmed by site-directed mutagenes

123 p of a series of imides, azinones (including AZT), inosines, and cyclic sulfonamides has been examine

124 cant NRTI-resistant HIV-1 mutants, including AZT (D67N/K70R/T215Y/K219Q), Tenofovir (K65R), and Lamiv

125 support the model that cn mutations increase AZT resistance by reducing template RNA degradation, the

126 (cn) of HIV-1 reverse transcriptase increase AZT resistance by altering the balance between nucleotid

127 e 11 RNase H primer grip mutations increased AZT resistance 20 to 243 times above WT levels in the co

128 agenesis: A371V and Q509L together increased AZT resistance approximately 10- to 50-fold in combinati

129 ate RNA degradation, which in turn increased AZT resistance.

130 Our results show that Q509L increases AZT-monophosphate (AZT-MP) excision activity of RT on RN

131 , suggesting that the T400 residue increases AZT resistance in CRF01_AE at least in part by directly

132 tation in the RNase H domain of RT increases AZT resistance and highlights how the polymerase and RNa

133 ersely, reverse transcriptase (RT) inhibitor AZT has a profound effect on the FOA dynamics and meioti

134 tibility to the nucleoside analog inhibitors AZT and 3TC.

135 the reverse transcriptase enzyme inhibitors AZT, ddI, 3TC, d4T, foscarnet, and nevirapine, as well a

136 he AZT P3Ms were substrate inhibitors, as is AZT triphosphate.

137 o wild-type strains during chronic low-level AZT exposure in minimal medium.

138 r cells from our patient and PEL cell lines, AZT selectively blocked nuclear entry of the NF-kappaB h

139 and remains in remission on oral maintenance AZT/GCV therapy 3 years after diagnosis.

140 ribavirin (546+/-37 nA, 61.0+/-13.2 microM), AZT (420+/-4 nA, 310+/-9 microM), and 3-deazauridine (50

141 lex glycans (60% of control at 20 micrometer AZT) and a significant accumulation of core-fucosylated

142 hesized a series of AZT triphosphate mimics (AZT P3Ms) and evaluated their inhibitory effects on HIV-

143 show that Q509L increases AZT-monophosphate (AZT-MP) excision activity of RT on RNA/DNA template/prim

144 ine (azidothymidine [AZT], -3.64 g/dL vs. no AZT, -2.08 g/dL), and patients receiving zidovudine had

145 related RBV dose reductions (AZT, 60% vs. no AZT, 16%).

146 d levels of total phosphorylated AZT and not AZT-TP.

147 istant to the nucleoside RT inhibitor (NRTI) AZT because of an increase in the level of excision of A

148 In the absence of AZT, the fitness cost conferred by D67N or K219Q was mod

149 The biological activities of AZT and D4T could be partially attributable to their inh

150 basis of the observed antiviral activity of AZT phosphoramidate monoesters 3a and 4a in PBMCs and CE

151 The affinity of AZT-resistant HIV-1 RT for AZTp4A is at least 30,000-fol

152 The 50% inhibitory concentration of AZT was determined to be 30 nM in this HTLV-1 replicatio

153 of exonuclease activity by concentrations of AZT-monophosphate known to occur in cells.

154 n MT-2 cells in increasing concentrations of AZT.

155 The proapoptotic effect of AZT and IFN-alpha in PEL occurs through the concomitant

156 dies establishing the biochemical effects of AZT resistance mutations in HIV-1 RT on the incorporatio

157 between T/P duplex length and efficiency of AZT excision demonstrated that RT could not efficiently

158 impact of secondary TAMs on the evolution of AZT resistance, we generated recombinant viruses from cl

159 ZT resistance is due to enhanced excision of AZT 5'-monophosphate (AZTMP) from the end of the primer

160 e of an increase in the level of excision of AZT monophosphate (AZTMP) from the primer.

161 ed efforts in clicking the 3'-azido group of AZT have not yielded 1,2,3-triazoles active against HIV

162 on its interactions with the azido group of AZT.

163 utation does not affect the incorporation of AZT 5'-triphosphate (AZTTP), either in the presence or t

164 s slow (0.0009 s(-1)) after incorporation of AZT.

165 Whereas IC(50) values for the inhibition of AZT-triphosphate incorporation by efavirenz were essenti

166 The inclusion of TDF instead of AZT and ATZ/r was correlated with lower rates of resista

167 The high level of AZT resistance exhibited by CRF01_AE was primarily assoc

168 time that CRF01_AE exhibits higher levels of AZT resistance in the presence of TAMs and that this res

169 ich in turn correlated with higher levels of AZT-monophosphate (AZTMP) excision on both RNA and DNA t

170 Quantitation of the intracellular levels of AZT-TP in PBMCs and CEM cells treated with 3a and 4a in

171 idine correlated the intracellular levels of AZT-TP to the antiviral activity and suggested that AZT-

172 rm colonies in the presence of low levels of AZT.

173 However, to date the mechanism of AZT action remains unclear and thus, reasons for treatme

174 Although the mechanism of AZT resistance involves enhanced excision, resistance to

175 A number of AZT P3Ms exhibited very potent inhibition of HIV-1 rever

176 the higher viral fitness in the presence of AZT and shows that these viruses are phenotypically diff

177 rolysis was not increased by the presence of AZT resistance mutations.

178 side-binding lectin RCA-I in the presence of AZT, suggesting that the addition of terminal sialic aci

179 D67N) or HXB2(D67N/K219Q) in the presence of AZT.

180 in quiescent cells, even in the presence of AZT.

181 ch blocks DNA replication in the presence of AZT.

182 pared and shown to inhibit the production of AZT-MP from cell-free extracts of CEM cells, further sug

183 Reaction of AZT with 2-chloro-4H-1,3,2-benzodioxaphosphorin-4-one, f

184 ellular substrate used during replication of AZT-resistant HIV is still unknown.

185 ctors associated with the rapid selection of AZT mutations in these viruses, we evaluated fitness dif

186 fully understood, although the selection of AZT resistance mutations in patients treated with d4T su

187 In vitro selection of AZT resistance showed that viruses with D67N and/or K219

188 hate mimics, we have synthesized a series of AZT triphosphate mimics (AZT P3Ms) and evaluated their i

189 erminus plays a role in M184V suppression of AZT resistance, while K65R suppression occurs through a

190 Several different types of AZT P3Ms containing alpha-P-thio (or dithio) and beta,ga

191 ptibility and increased rescue efficiency on AZT- or tenofovir-terminated primers, as compared with t

192 Importantly, HIV patients on AZT treatment demonstrate augmented MRP4-CFTR complex fo

193 ects on TDF, 3438 on d4T and 709 subjects on AZT.

194 navir during pregnancy and breastfeeding) or AZT/sdNVP (zidovudine until delivery with single-dose ne

195 in vitro experiments in which HIV-1(LAI) or AZT-resistant HIV-1(LAI) (M41L/L210W/T215Y) was passaged

196 ve effect was observed with AZT-resistant or AZT/3TC dually resistant RT and several drugs (i.e., AZT

197 Other AZT-hypersusceptible mutants were resistant to PFA and a

198 mutations to wild-type RT and the two other AZT-resistant variants described above.

199 with reduced levels of total phosphorylated AZT and not AZT-TP.

200 egression confirmed that first-line EFV plus AZT (reference) was associated with a higher median haza

201 x years after treatment initiation, EFV plus AZT showed the highest cumulative resistance incidence (

202 atio [HR], 0.57; range, 0.42-0.76), LPV plus AZT (HR, 0.63; range, 0.45-0.89), LPV plus TDF (HR, 0.55

203 ofovir (TDF) (n = 615); lopinavir (LPV) plus AZT (n = 573); LPV plus TDF (n = 301); and ritonavir-boo

204 PPi-mediated excision produces AZT-5'-triphosphate (AZTTP), which could be immediately

205 K65R reduced AZT resistance from >50-fold to <2.5-fold in both backgr

206 had more anemia-related RBV dose reductions (AZT, 60% vs. no AZT, 16%).

207 for wild-type (WT) RT and an AZT-resistant (AZT(R)) RT containing a thymidine analog mutation set-D6

208 orolytic excision of AZTMP by AZT-resistant (AZT(R)) RT.

209 00 residue in CRF01_AE with alanine restored AZT sensitivity and reduced AZTMP excision on both RNA a

210 e physical mixture containing FLT-succinate, AZT, 3TC, and glutamic acid exhibited 115-fold less acti

211 phosphorolytic excision of chain-terminating AZT-5'-monophosphate (AZTMP).

212 phorolytic excision of the chain-terminating AZT-5'-monophosphate (AZTMP).

213 muM) exhibited higher anti-HIV activity than AZT and 3TC against cell-free virus.

214 MP and PMPA at lower ATP concentrations than AZT-R or SSGR/T215Y, suggesting that a virus containing

215 significantly more virological failure than AZT/3TC/NVP; a third study was terminated prematurely be

216 analogues (1-5 and 7) were more potent than AZT but less active than DCK.

217 rac-1h-TP was slightly more potent than AZT-5'-triphosphate against wild-type HIV RT, suggesting

218 9.5 nM and at least 20-fold more stable than AZT triphosphate in the serum and cell extracts.

219 We find that AZT and ddC treatment leads to greater depletion of mito

220 Clinical findings show that AZT resistance mutations in HIV-1 reverse transcriptase

221 d as incubation time increases, showing that AZT induces the sized transformation of membrane permeab

222 to the antiviral activity and suggested that AZT-TP was responsible for the activity observed.

223 The AZT resistance mutations serve to increase the affinity

224 with a series of nucleophiles, afforded the AZT 5'-beta,gamma-difluoromethylene-gamma-substituted tr

225 When tested against the AZT-resistant mutant, all NNRTIs inhibited removal by gr

226 ifference in IC(50) was observed between the AZT-monophosphate excision reactions, the RNA/DNA T/P su

227 In particular, how do the AZT resistance mutations enhance excision, and what mech

228 ARV arm was significantly lower than in the AZT/sdNVP arm (15.7% vs 28.3%; P = .001), but the risks

229 All of the AZT-resistant variants we tested excise AZTMP and 9-[2-(

230 ta,gamma-bridge of triphosphate rendered the AZT P3Ms 6b-6f with varied activities (K(i) from 9.5 to

231 ressed by antisense hTR, confirming that the AZT effect in parent FaDu cells is mediated through telo

232 The results imply that the AZT P3Ms were substrate inhibitors, as is AZT triphospha

233 gs currently approved for antiviral therapy: AZT, ddC, D4T, 3TC and carbovir.

234 Detailed biochemical studies on one of these AZT-resistant variants, His285 to Asp, have shown that t

235 independent of ATP for decreased binding to AZT-triphosphate.

236 d nucleotide excision efficiency compared to AZT, which along with molecular modeling suggests a mech

237 ted extent, and this activity contributes to AZT resistance.

238 The mutations that lead to AZT resistance enhance ATP binding and, in so doing, enh

239 ty of 3a and 4a toward CEM cells relative to AZT correlated with reduced levels of total phosphorylat

240 that mutations correlated with resistance to AZT (D67N/K70R/T215F/K219Q) confer resistance to the 3'-

241 criptase (RT), which increases resistance to AZT in combination with the thymidine analogue mutations

242 s, likely reflecting low-level resistance to AZT that is not detectable by phenotypic testing.

243 th known mutations that confer resistance to AZT, similar to those genotypes found in the patient.

244 n of AZTMP associated with HIV resistance to AZT.

245 e of the mutations that confer resistance to AZT.

246 nhancement (6- to 11-fold) in sensitivity to AZT-resistant viruses.

247 This sensitization to AZT is seen both in the presence and the absence of the

248 nthetic genetic interactions for survival to AZT or ciprofloxacin exposure were observed between RadA

249 all were found to have WT susceptibility to AZT, and all replicated efficiently as WT HIV-1(T215).

250 us containing this RT remains susceptible to AZT inhibition.

251 The faster evolution of these mutants toward AZT resistance is consistent with the higher viral fitne

252 gue 3'-azido-3'-deoxythymidine triphosphate (AZT-TP) had no effect, whereas the pyrophosphate analogu

253 -beta,gamma-(difluoromethylene)triphosphate (AZT 5'-alphaB-betagammaCF(2)TP) (6d-I), is as potent as

254 of 2',3'-dideoxy-TTP (ddTTP), 3'-azido-TTP (AZT-TP), 2',3'-dideoxy-CTP (ddCTP), 2',3'-didehydro-TTP

255 ns from different subtypes can underestimate AZT resistance levels, and they emphasize the need to de

256 do-3'-deoxythymidine (AZT)-resistant variant AZT-R (M41L/D67N/K70R/T215Y/K219Q) and a variant contain

257 scriptase (RT) level and corresponding viral AZT resistance.

258 T), in which 78% of the reaction product was AZT diphosphate.

259 lpha,beta-bridge of triphosphate led to weak AZT P3M inhibitors.

260 resistance relative to wild-type B, whereas AZT resistance of subtype B containing the same TAMs was

261 ciently as natural deoxynucleotides, whereas AZT-TP, 3TC-TP, and CBV-TP were only moderate inhibitors

262 Because it is not known whether AZT selects for mutations outside of the polymerase doma

263 se or switching templates prematurely, while AZT(R) RT primarily misaligned the primer strand, causin

264 Mice (C57Bl/6) were administered with AZT (Zidovudine 100 mg/kg/day), 3TC (Lamivudine 50 mg/kg

265 el, several of the mutations associated with AZT resistance act primarily to enhance the binding of A

266 nt Q161L/H208Y) alone or in combination with AZT resistance mutations.

267 ogression following cessation (compared with AZT/sdNVP).

268 rnet resistance and directly correlated with AZT resistance.

269 HIV variant (9-fold compared to 56-fold with AZT).

270 s, a multiplicative effect was observed with AZT-resistant or AZT/3TC dually resistant RT and several

271 nd 23.0% (95% CI, 17.8-29.5) progressed with AZT/sdNVP, whereas few women in either arm (<5%) with in

272 on of virus was comparable to that seen with AZT when moi <or= 0.005.

273 In vitro selection with AZT showed that HIV-1(215D) and HIV-1(215C) acquired 215

274 se H domains were not selected starting with AZT-resistant virus (M41L/L210W/T215Y).

275 d floxuridine) also act synergistically with AZT.

276 lace of IFN-alpha) similarly synergized with AZT to induce apoptosis in HHV-8 positive PEL cells.

277 block and extend DNA primers terminated with AZT and other NRTIs, when complexed with RNA or DNA temp

278 lly to inhibit enzyme activity together with AZT-triphosphate.

279 p53 enter remission following treatment with AZT, those with a mutated p53 did not respond, and patie

280 istance to the nucleoside analog zidovudine (AZT), HIV-2 RT does not appear to use this pathway.

281 Stavudine (d4T) and zidovudine (AZT) are thymidine analogs widely used in the treatment

282 witches from stavudine (d4T) and zidovudine (AZT) regimens have been well described but data on tenof

283 ch a mutagen, 3'-azidothymidine [zidovudine (AZT)], used widely in the treatment and prevention of HI

284 iously been demonstrated between zidovudine (AZT)-triphosphate resistance data at the reverse transcr

285 lovir (ACV), cytarabine (Ara-C), zidovudine (AZT) and zalcitabine (ddC)-we show that TDP1 is capable

286 udine (3TC) > tenofovir (PMPA) > zidovudine (AZT) > abacavir (metabolized to carbovir, CBV).

287 e (AZTMP) in vitro and increases zidovudine (AZT) resistance in vivo.

288 was done for 220 HIV-1-infected, zidovudine (AZT)-exposed pregnant women and 24 of their infected inf

289 se transcriptase (RT) inhibitors zidovudine (AZT) and tenofovir and the integrase inhibitor raltegrav

290 ritonavir, indinavir, lopinavir, zidovudine (AZT), abacavir, stavudine, didanosine (ddI), and lamivud

291 The NRTIs zidovudine (AZT), stavudine (d4T), didanosine (ddI), and lamivudine

292 antiviral therapy consisting of zidovudine (AZT) and ganciclovir (GCV; MST 41.3 +/- 3.3 days; P = 0.

293 he incorporation and excision of zidovudine (AZT) by HIV-1 RT using DNA/DNA and RNA/DNA T/Ps that wer

294 lovir, and the 5'-valyl ester of zidovudine (AZT), was purified from Caco-2 cells derived from human

295 icitabine): efavirenz (EFV) plus zidovudine (AZT) (n = 524); EFV plus tenofovir (TDF) (n = 615); lopi

296 only recently been proposed that zidovudine (AZT) resistance can involve the excision of the nucleosi

297 We recently reported that zidovudine (AZT) selected for the Q509L mutation in the ribonuclease

298 ther the wild-type (WT) T or the zidovudine (AZT)-selected T215Y/F.

299 ll were found to be sensitive to zidovudine (AZT) and other drugs.

300 ne and/or hypersusceptibility to zidovudine (AZT).

301 decreased hypersusceptibility to zidovudine (AZT; 1.4-2.2-fold).