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(R) RT did not excise terminal nucleotides more frequ

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

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

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

13 AZT-MP and substantial amounts of either phosphoramidate

14 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

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

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

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

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

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

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

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

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

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

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

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

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

27 (-)2',3'-dideoxy-3'-thiacytidine (3TC), and AZT-resistant HIV-1 reverse transcriptase (RT) can incre

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

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

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

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

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

33 e reverse transcriptase inhibitors ddITP and AZT-TP to the telomeric end, causing chain termination.

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 ause increased sensitivity to NRTIs, such as AZT.

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

46 ,3'-ddC (AZddC), 3'-azido-2',3'-ddG (AZddG), AZT, and 3'-azido-2',3'-ddU (AZddU).

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

48 3'-Azidothymidine (AZT) was the first approved antiviral for the treatment

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

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

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

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

53 ptor antagonist A438079, and azidothymidine (AZT) were tested in HIV-1-infected human tonsil explants

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

55 containing stavudine (d4T), azidothymidine (AZT) and TDF on death and attrition among HIV patients w

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

57 erse transcriptase inhibitor azidothymidine (AZT).

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

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

60 bine (ara-C) and zidovudine (Azidothymidine, AZT).

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

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

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

64 at microhomologies were enhanced modestly by AZT.

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

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

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

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

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

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

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

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

73 ifferent when compared to the ART containing AZT (AHR = 0.91, 95% CI: 0.69-1.20).

74 h the ART containing d4T, the ART containing AZT was significant and not significant associated with

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

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

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

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

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

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

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

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

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

84 1 resistance to 3'-azido-3'-deoxythymidine (AZT) involves reverse transcriptase (RT)-catalyzed phosp

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

110 ent emergence with combinations that exclude AZT.

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

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

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

114 ision reaction to be relatively specific for AZT?

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

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

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

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

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

120 (+)3TC approximately equal to (-)3TC > CBV > AZT > PMPA approximately equal to d4T >> ddA (ddI) >> dd

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

137 Remarkably, reverse transcriptase inhibitor AZT-treated Chk2 mutant oocytes that evade FOA initially

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

165 on its interactions with the azido group of AZT.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

181 ch blocks DNA replication in the presence of AZT.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

196 ining d4T (AHR = 0.72, 95% CI: 0.60-0.86) or AZT (AHR = 0.67, 95% CI: 0.58-0.77).

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

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

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

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

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

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

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

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

205 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

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

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

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

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

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

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

212 00 residue in CRF01_AE with alanine restored AZT sensitivity and reduced AZTMP excision on both RNA a

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

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

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

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

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

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

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

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

221 9.5 nM and at least 20-fold more stable than AZT triphosphate in the serum and cell extracts.

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

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

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

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

226 The AZT resistance mutations serve to increase the affinity

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

247 n of AZTMP associated with HIV resistance to AZT.

248 e of the mutations that confer resistance to AZT.

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

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

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

252 us containing this RT remains susceptible to AZT inhibition.

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

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

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

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

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

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

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 erase-negative cell lines when compared with AZT treatment.

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

269 rnet resistance and directly correlated with AZT resistance.

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

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

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

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

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

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

276 d floxuridine) also act synergistically with AZT.

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

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

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

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

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