ライフサイエンスコーパス: NNRTI

1 NNRTI concentrations were measured by sensitive high-per

2 NNRTI regimen choice and preexisting NNRTI-resistant min

3 NNRTI resistance was particularly high in children expos

4 NNRTIs are noncompetitive inhibitors that bind in a hydr

5 NNRTIs are recommended components of highly active antir

6 NNRTIs modestly affect liver stage Plasmodium parasites,

7 9%] of 597 patients without TAMs; p<0.0001), NNRTI resistance (107 [93%] vs 462 [77%]; p<0.0001), and

8 ruption, 22/131 (16.8%) patients showed >/=1 NNRTI-RAM, including eight patients with NNRTI-RAMs dete

9 tions, compared to the use of 2 NRTIs plus 1 NNRTI.

10 hiral indolyarylsulfones (IASs) as new HIV-1 NNRTIs.

11 children randomised to WHO-recommended 2NRTI+NNRTI long-term ART, 308/378 (81%) monitored with CD4 co

12 ily in the nonfunctional, solvent-accessible NNRTI binding pocket.

13 MTCT), a substantial proportion will acquire NNRTI-resistant HIV, potentially compromising response t

14 s) were continued for median nine days after NNRTI interruption, did not prevent NNRTI-RAMs, but incr

15 Four weeks after NNRTI interruption, 19/31 (61.3%) and 34/39 (87.2%) pati

16 d in cellulo antiretroviral activity against NNRTI-resistant strains.

17 istant C181 lineage also resulted in altered NNRTI sensitivity and a net fitness cost.

18 NNRTI strategy"), all individuals who had an NNRTI-resistance mutation identified by ultra-deep seque

19 ch a switch compared with continuation of an NNRTI-containing regimen.

20 50 copies per mL for at least 6 months on an NNRTI plus emtricitabine and tenofovir regimen.

21 apy after first-line virologic failure on an NNRTI regimen.

22 be a suitable alternative for patients on an NNRTI with emtricitabine and tenofovir regimen consideri

23 dues involved in template/primer binding and NNRTI binding.

24 08.2; P<.0001), while protease inhibitor and NNRTI replacement rates were similar.

25 drug resistance, primarily due to M184V and NNRTI mutations, has been identified in 60%-72%, althoug

26 z-containing therapy in both NNRTI-naive and NNRTI-experienced patients and to determine their associ

27 vity against multidrug (IC(50) = 5.9 nM) and NNRTI (IC(50) = 12.9 nM) resistant viruses than parent n

28 DR to PI and NRTI was seen in 1.6%, NRTI and NNRTI in 3.4%, and triple class TDR in 0.9%.

29 mutations; and 30 (66.7%) had both NRTI and NNRTI mutations.

30 ptase (RT) mutation associated with NRTI and NNRTI resistance, respectively.

31 N and RH mutations can exhibit dual NRTI and NNRTI resistance.

32 in drug-resistance patterns in both NRTI and NNRTI were observed by site.

33 Both PI and NNRTI use was associated with increases in APRI over tim

34 ed in gag and in gp41-CD in both the PI- and NNRTI-treated groups.

35 Resistance-associated mutations (RAMs) and NNRTI concentrations were studied in plasma from 132 pat

36 mplexes is hindered by a kinetic barrier and NNRTIs mostly interact with free RT.

37 hinge points for this essential motion, and NNRTIs therefore act as "molecular wedges," sterically b

38 reverse transcriptase inhibitors (NRTIs and NNRTIs).

39 reverse transcriptase inhibitors (NRTIs and NNRTIs).

40 ecular mechanisms of resistance to NRTIs and NNRTIs, and their complex relationships, may help in des

41 Additionally, we showed that another NNRTI, nevirapine (NVP), stimulated K101E+G190S virus re

42 rilpivirine, the most recently FDA-approved NNRTI, bear a cyanovinylphenyl (CVP) group.

43 nd have lower cytotoxicity than the approved NNRTI drugs efavirenz and rilpivirine.

44 -Saharan Africa at any prevalence of pre-ART NNRTI resistance.

45 the risk of viral failure at week 48 between NNRTI and bPI (P = .19).

46 At week 48, the overall difference between NNRTI- and PI-based regimens in selection of any major N

47 difference in prevalence of M184V/I between NNRTI and PI (crude unweighted prevalence 3.2% vs 1.4%);

48 To explore potential interactions between NNRTI and INSTI resistance mutations, we investigated th

49 nalysis to evaluate the relationship between NNRTI-resistant minority variants and the likelihood and

50 ltidrug efavirenz-containing therapy in both NNRTI-naive and NNRTI-experienced patients and to determ

51 f sub-Saharan Africa; this rise is driven by NNRTI resistance in studies from east and southern Afric

52 tance to nevirapine or efavirenz imparted by NNRTI mutations.

53 mpound I and efavirenz, the standard of care NNRTI.

54 the observation that mutant viruses carrying NNRTI plus INSTI resistance mutations had reduced amount

55 We characterized NNRTI and TMP-SMX effects on Plasmodium liver stages in

56 ference in prevalence of K65R when comparing NNRTI (1.3%) with PI (0.67%); absolute weighted differen

57 tion of the NNIBP that may be used to design NNRTIs.

58 TI) and a TMC-derivative (a diarylpyrimidine NNRTI) linked via a poly(ethylene glycol) (PEG) linker.

59 tance is dependent upon the affinity of each NNRTI to the RT and further influenced by the presence o

60 hus, the development of novel more effective NNRTIs as anti-HIV-1 agents with fewer long-term liabili

61 ce, also reduce RNase H cleavage and enhance NNRTI resistance in the context of the patient RT pol do

62 the resumption of DNA synthesis and enhanced NNRTI resistance.

63 etween RT and IN mutations are important for NNRTI and INSTI resistance and viral fitness.

64 DR-associated mutations were more common for NNRTIs (5.4%), followed by nucleoside reverse transcript

65 e patterns on susceptibility was largest for NNRTIs.

66 Four NNRTI SDRMs-K101E, K103N, Y181C, and G190A-accounted for

67 guided design to develop two next-generation NNRTI drug candidates, compounds I and II, which are mem

68 o examine the prevalence of 1(st)-generation NNRTI resistance in Europe, the United States (US), and

69 inhibits HIV-1 resistant to first generation NNRTIs.

70 ome a barrier to the use of 1(st)-generation NNRTIs and the increased costs associated with regimen f

71 Resistance to 1(st)-generation NNRTIs is found among treated and untreated HIV-infected

72 n which more than 10% of ART initiators have NNRTI resistance.

73 everse-transcriptase inhibitors (hereafter, "NNRTI strategy"), all individuals who had an NNRTI-resis

74 ariable logistic regression analysis, higher NNRTI minority variant copy numbers, non-white race, and

75 of an RT-DNA-nevirapine complex revealed how NNRTI binding forbids RT from forming a polymerase compe

76 scence anisotropy approaches to discover how NNRTIs modulate the intra-molecular conformational chang

77 e were detected more often at study entry in NNRTI-experienced patients than NNRTI-naive patients by

78 ugh 2013, driven primarily by an increase in NNRTI resistance.

79 TI-resistant variants were more prevalent in NNRTI-experienced patients and were associated with redu

80 tant with NNRTI BP mutants further increases NNRTI resistance from 3- to 30-fold, supporting the role

81 eoside reverse-transcriptase (RT) inhibitor (NNRTI) resistance mutations (from 0.3% to 7.1%), particu

82 eoside reverse transcriptase (RT) inhibitor (NNRTI) that efficiently inhibits HIV-1 resistant to firs

83 nnucleoside reverse transcriptase inhibitor (NNRTI) and a common component of clinically approved ant

84 -nucleoside reverse transcriptase inhibitor (NNRTI) based FDC of rilpivirine plus tenofovir disoproxi

85 -nucleoside reverse transcriptase inhibitor (NNRTI) binding site.

86 -nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz (EFV) showed subunit-specific perturbat

87 nnucleoside reverse transcriptase inhibitor (NNRTI) MIV-150 in carrageenan reduced vaginal infection

88 nnucleoside reverse transcriptase inhibitor (NNRTI) mutations (2.9%) and protease inhibitor mutations

89 nnucleoside reverse-transcriptase inhibitor (NNRTI) mutations (hazard ratio, 77.5; 95% confidence int

90 -nucleoside reverse transcriptase inhibitor (NNRTI) or 3 NRTIs as long-term ART.

91 -nucleoside reverse transcriptase inhibitor (NNRTI) or who are on a multitablet NNRTI-containing regi

92 nnucleoside reverse-transcriptase inhibitor (NNRTI) regimen in Africa and Asia, comparing the genotyp

93 -nucleoside reverse-transcriptase inhibitor (NNRTI) resistance in people initiating antiretroviral th

94 nnucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations are associated with an incre

95 nnucleoside reverse-transcriptase inhibitor (NNRTI) resistance, and 4.2% had protease inhibitor (PI)

96 nnucleoside reverse transcriptase inhibitor (NNRTI) resistance.

97 -nucleoside reverse transcriptase inhibitor (NNRTI) resistance.

98 -nucleoside reverse transcriptase inhibitor (NNRTI), rilpivirine (TMC278; Tibotec Pharmaceuticals, Co

99 nnucleoside reverse transcriptase inhibitor (NNRTI)- or lopinavir/ritonavir (LPV/r)-based regimen wer

100 nnucleoside reverse-transcriptase inhibitor (NNRTI)-based (hazard ratio, 7.10; 95% confidence interva

101 nnucleoside reverse-transcriptase inhibitor (NNRTI)-based ART.

102 -nucleoside reverse transcriptase inhibitor (NNRTI)-based highly active antiretroviral therapy (HAART

103 -nucleoside reverse-transcriptase inhibitor (NNRTI)-based regimen to one including a protease inhibit

104 nnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens with a backbone of tenofovir/emtri

105 nnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens.

106 nnucleoside reverse-transcriptase inhibitor (NNRTI)-based therapy suggest that 76%-90% of living pati

107 -nucleoside reverse transcriptase inhibitor (NNRTI)-resistant mutants have been shown to emerge after

108 nnucleoside reverse-transcriptase inhibitor (NNRTI)-resistant variants at the initiation of multidrug

109 nnucleoside reverse-transcriptase inhibitor (NNRTI)-resistant variants on the risk of virologic failu

110 -nucleoside reverse transcriptase inhibitor (NNRTI).

111 nnucleoside reverse transcriptase inhibitor (NNRTI; N = 52) or protease inhibitor (PI; N = 42).

112 -nucleoside reverse transcriptase inhibitor (NNRTI; nevirapine or efavirenz) in sub-Saharan Africa.

113 is pocket binds nonnucleoside RT inhibitors (NNRTI); therefore, NNRTI sensitivity was used to probe e

114 oside reverse transcriptase (RT) inhibitors (NNRTI) and integrase (IN) strand transfer inhibitors (IN

115 nucleoside reverse transcriptase inhibitors (NNRTI) 3 and 4 with HIV-1 reverse transcriptase (RT).

116 nucleoside reverse transcriptase inhibitors (NNRTI) efavirenz (EFV) and nevirapine (NVP) in first-lin

117 nucleoside reverse transcriptase inhibitors (NNRTI) in east Africa (36% per year [21 to 52]; p<0.0001

118 nucleoside reverse transcriptase inhibitors (NNRTI), which are similar in structure to earlier descri

119 nucleoside reverse transcriptase inhibitors (NNRTI; Efavirenz, Etravirine, Rilpivirine and Nevirapine

120 (NRTIs) and five non-nucleoside inhibitors (NNRTIs) are approved HIV-1 drugs.

121 elopment of novel non-nucleoside inhibitors (NNRTIs) with activity against variants of HIV reverse tr

122 sms compared to nonnucleoside RT inhibitors (NNRTIs) and nucleoside/nucleotide RT inhibitors (NRTIs).

123 Non-nucleoside RT inhibitors (NNRTIs) are a class of highly specific drugs which bind

124 n of RT and of non-nucleoside RT inhibitors (NNRTIs) by isothermal titration calorimetry (ITC).

125 nucleoside and non-nucleoside RT inhibitors (NNRTIs) by mechanisms that are not well understood.

126 sistance to the nonnucleoside RT inhibitors (NNRTIs) nevirapine and delavirdine.

127 de (NRTIs) and non-nucleoside RT inhibitors (NNRTIs) when combined with certain mutations.

128 s resistant to non-nucleoside RT inhibitors (NNRTIs), suggesting the involvement of binding site(s) o

129 he discovery of nonnucleoside RT inhibitors (NNRTIs).

130 oside reverse transcriptase (RT) inhibitors (NNRTIs) are hindered by their unsatisfactory pharmacokin

131 oside reverse transcriptase (RT) inhibitors (NNRTIs) are important components of multidrug therapy fo

132 oside reverse transcriptase (RT) inhibitors (NNRTIs) are routinely used to treat HIV-1 infection, yet

133 nucleoside reverse transcriptase inhibitors (NNRTIs) and 2 protease inhibitors (PIs).

134 nucleoside reverse transcriptase inhibitors (NNRTIs) are potent and commonly prescribed antiviral age

135 nucleoside reverse transcriptase inhibitors (NNRTIs) are usually part of first-line treatment regimen

136 nucleoside reverse transcriptase inhibitors (NNRTIs) efavirenz and nevirapine are commonly used in fi

137 nucleoside reverse transcriptase inhibitors (NNRTIs) has been associated with baseline human immunode

138 nucleoside reverse transcriptase inhibitors (NNRTIs) have been observed among previously untreated in

139 nucleoside reverse transcriptase inhibitors (NNRTIs) have inherent flexibility, helping to maintain a

140 nucleoside reverse transcriptase inhibitors (NNRTIs) in pregnant and breastfeeding women will result

141 nucleoside reverse transcriptase inhibitors (NNRTIs) measured in the population starting ART.

142 nucleoside reverse transcriptase inhibitors (NNRTIs) might compromise HIV control in low-income and m

143 nucleoside reverse transcriptase inhibitors (NNRTIs) play a central role in the treatment of AIDS, bu

144 nucleoside reverse transcriptase inhibitors (NNRTIs) reached 45% (95% CI: 27-64%) in 2015, all based

145 nucleoside reverse transcriptase inhibitors (NNRTIs) that target the viral polymerase have been a key

146 nucleoside reverse-transcriptase inhibitors (NNRTIs) was observed among VCT clients aged 18-21 years.

147 nucleoside reverse transcriptase inhibitors (NNRTIs) with a novel aryl-phospho-indole (APhI) scaffold

148 nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs) among primigravid

149 nucleoside reverse transcriptase inhibitors (NNRTIs), and their biological activity was evaluated.

150 nucleoside reverse transcriptase inhibitors (NNRTIs), nucleotide substrates, Mg ions, temperature, an

151 nucleoside reverse transcriptase inhibitors (NNRTIs).

152 nucleoside reverse transcriptase inhibitors (NNRTIs).

153 nucleoside reverse transcriptase inhibitors [NNRTIs]), integrase strand transfer inhibitors, and viru

154 nucleoside reverse transcriptase inhibitors [NNRTIs], and 60.3% [P = 0.94] in patients receiving NNRT

155 dictive of reduced susceptibility to initial NNRTI-based regimens: 4.5% and 6.5% of patient isolates

156 involving ART-naive participants initiating NNRTI-based regimens were included.

157 up O lineage resulted in a loss of intrinsic NNRTI resistance and was accompanied by fitness loss.

158 resistance mutations, particularly involving NNRTI resistance, were significantly associated with a d

159 ons in both groups, suggesting that isolated NNRTI-associated transmitted drug resistance may not be

160 r individuals to whom variants with isolated NNRTI-associated drug resistance were transmitted are at

161 ce mutations in 33 individuals with isolated NNRTI-associated transmitted drug resistance and 49 matc

162 alogue mutations (T215F, D67N, K70R, K219Q), NNRTIs (L100I, Y181C, K103N, V108I, Y188L), and PIs (V82

163 g the Incoming Nucleotide Binding, Knuckles, NNRTI Adjacent, and 399 sites, located in the polymerase

164 Three of these sites (Knuckles, NNRTI Adjacent, and Incoming Nucleotide Binding) are inh

165 regimen compared with zidovudine/lamivudine/NNRTI, PI resistance at switch (6.69; 2.49-17.98; P < .0

166 al failure of the WHO-recommended first-line NNRTI-based regimen was higher in the presence of K103N.

167 inst RT variants carrying one of three major NNRTI resistance mutations: K103N, Y181C, or G190A.

168 Minor NNRTI-resistant variants were more prevalent in NNRTI-ex

169 103N and Y181C) to detect and quantify minor NNRTI-resistant variants.

170 3.0% and 8.8% having resistance to 1 or more NNRTI or nucleoside reverse transcriptase inhibitors, re

171 nhibitor (NNRTI) or who are on a multitablet NNRTI-containing regimen and want a regimen simplificati

172 re 1.3, 1.9, and 2.2 years in the ART-naive, NNRTI, and PI groups, respectively (P = .01).

173 ong potential for further development as new NNRTIs for the potential treatment of HIV infection.

174 ent results highlight the chiral IASs as new NNRTIs with improved resistance profile against the muta

175 ce in untreated patients and impact on newer NNRTIs.

176 nfection similar to EFV, but that the newest NNRTI, etravirine (ETR), did not.

177 ological failure during treatment with a non-NNRTI-containing regimen, we identified minority variant

178 ological failure during treatment with a non-NNRTI-containing regimen.

179 The short and practical synthesis of novel NNRTI relies on two sequential Pd-catalyzed aminations a

180 tor (NRTI) mutations; 33 (73%) had non-NRTI (NNRTI) mutations; and 30 (66.7%) had both NRTI and NNRTI

181 ingly, two subjects had major DRMs to NRTIs, NNRTIs, and 4 mutations in the Gag P2/NC CS.

182 lass TDR was 10.0%, 5.1%, and 1.6% to NRTIs, NNRTIs, and PIs.

183 Triple-class resistance to NRTIs, NNRTIs, and PR inhibitors was observed in 24 (53%) patie

184 nucleotide analog (NRTI) and non-nucleoside (NNRTI) drugs used in treating HIV-1 infections.

185 C was received by 67% of PI users and 69% of NNRTI users.

186 103N, Y181C, and G190A-accounted for >80% of NNRTI-associated TDR in all regions and subtypes.

187 In SSA and SSEA, 89% of NNRTI SDRMs were associated with high-level resistance t

188 The degree of NNRTI and NRTI resistance after first-line virologic fai

189 se data are promising for the development of NNRTI-containing gels to prevent rectal HIV transmission

190 RTI resistance and also offset the effect of NNRTI resistance mutations thereby restoring NNRTI bindi

191 Understanding the effect of NNRTI-resistant mutants on virus replication and reverse

192 reased risk of resistance-related failure of NNRTI/NRTI second-line regimens.

193 e detailed understanding of the mechanism of NNRTI inhibition and the effect of binding upon domain m

194 A small number of NNRTI-resistance mutations were responsible for most cas

195 The odds of NNRTI-associated TDR also increased in Latin America/Car

196 The adjusted odds ratio (OR) of NNRTI-RAM detection was 7.62 (95% confidence interval [C

197 The long-term persistence of NNRTI and protease inhibitor mutations suggests a risk f

198 Minor populations of NNRTI-resistant variants that were missed by standard ge

199 RT and further influenced by the presence of NNRTI-binding pocket (BP) mutants.

200 risk of virologic failure in the presence of NNRTI-resistant minority variants.

201 men became cost effective at a prevalence of NNRTI resistance higher than 15%, for cost-effectiveness

202 The reported prevalence of NNRTI resistance was generally higher in US/Canada than

203 argely on the country-specific prevalence of NNRTI resistance.

204 activity (EC50<1 nM) against a wide range of NNRTI-resistant viruses and a favorable pharmacokinetic

205 an region could face an unidentified rise of NNRTI-resistant HIV.

206 ne use were associated with a higher risk of NNRTI resistance at virologic failure.

207 e from 3- to 30-fold, supporting the role of NNRTI-RT affinity in our NNRTI resistance model.

208 l structure data suggest that the binding of NNRTIs forces RT into a wide-open conformation in which

209 Binding of NNRTIs to preformed RT/DNA complexes is hindered by a ki

210 rpretation of the mechanism of inhibition of NNRTIs.

211 fect of the reduction in RNase H cleavage on NNRTI resistance is dependent upon the affinity of each

212 users (8% per 5 years, 95% CI, -3%, 19%) or NNRTI users (3% per 5 years, 95% CI, -7%, 12%).

213 61 individuals with VF on a PI/r (n = 40) or NNRTI (n = 20) containing regimen.

214 d to either lopinavir-ritonavir-based ART or NNRTI-based ART and were followed for 6 months to 2 year

215 nitiated antiretroviral therapy with a PI or NNRTI and a backbone containing either TDF/FTC or ABC/3T

216 sistance to tenofovir, cytosine analogue, or NNRTIs.

217 For the other NNRTI mutants, reductions in RT content decreased both p

218 mong studied drugs, Efavirenz, but not other NNRTIs, altered claudin-5 expression, increased endothel

219 porting the role of NNRTI-RT affinity in our NNRTI resistance model.

220 these results confirm key predictions of our NNRTI resistance model and provide support for a unifyin

221 NNRTI regimen choice and preexisting NNRTI-resistant minority variants were both associated w

222 ing supports the use of EFV as the preferred NNRTI in first-line treatment regimen for HIV treatment,

223 e were substantial increases in pretreatment NNRTI resistance per year in all regions.

224 nd considered the prevalence of pretreatment NNRTI drug resistance in 2017.

225 her, and with the prevalence of pretreatment NNRTI resistance greater than 10%, a policy to measure v

226 Prevalence estimates of pretreatment NNRTI resistance in 2016 were 11.0% (7.5-15.9) in southe

227 In 2016, the prevalence of pretreatment NNRTI resistance was near WHO's 10% threshold for changi

228 respective of the prevalence of pretreatment NNRTI resistance, because of the increased cost of the p

229 articipants who had low- and high-prevalence NNRTI-resistant variants.

230 ys after NNRTI interruption, did not prevent NNRTI-RAMs, but increased detection of NRTI-RAMs (OR 4.2

231 170 received the study regimen: 86 received NNRTI-based ART, and 84 lopinavir-ritonavir-based ART.

232 lts (55% female) were enrolled: 20 receiving NNRTI-based and 20 receiving LPV/r-based treatment.

233 eligible for ART or were currently receiving NNRTI-based ART were randomly assigned to either lopinav

234 00 (90% CI, .92-1.09) for patients receiving NNRTI- and LPV/r-based treatment, respectively.

235 , and 60.3% [P = 0.94] in patients receiving NNRTIs only).

236 o observed that K103N, a clinically relevant NNRTI resistance mutation, does not prevent binding betw

237 After restarting NNRTI-based ART (n = 90), virologic suppression rates <4

238 NNRTI resistance mutations thereby restoring NNRTI binding.

239 rm high-affinity dead-end complexes, both RT/NNRTI/DNA complexes being unable to bind the incoming nu

240 Once formed, RT/NNRTI complexes bind DNA either in a seemingly polymeras

241 HIV-1-specific nonnucleoside RTIs (NNRTIs), protease inhibitors (PIs), and integrase inhibi

242 Our data showed NNRTI treatment modestly reduced P. yoelii liver stage p

243 (IC50) of EFV than viruses carrying a single NNRTI mutation.

244 We measured the fitness of six NNRTI-resistant mutants, the K103N, V106A, Y181C, G190A,

245 ble for the development of extended-spectrum NNRTIs.

246 STRATEGY-NNRTI is a 96 week, international, multicentre, randomis

247 to emerge after interruption of suppressive NNRTI-based antiretroviral therapy (ART) using routine t

248 udy entry in NNRTI-experienced patients than NNRTI-naive patients by both single-genome sequencing (8

249 We found that NNRTI binding to RT induces opening of the fingers and t

250 e most recent time-based trends suggest that NNRTI-resistance prevalence may be stable or decreasing.

251 It is widely believed that NNRTIs function as "molecular wedges", disrupting the re

252 The NNRTI resistance mutations had no effect on RAL suscepti

253 a9-strand that involve the YMDD loop and the NNRTI binding pocket.

254 e design of more effective inhibitors at the NNRTI site and also drive the identification of novel al

255 and tenofovir (switch group) or continue the NNRTI plus emtricitabine and tenofovir regimen (no-switc

256 ors (IIs) did not affect HK2, except for the NNRTI etravirine (ETV).

257 ase H cleavage and provide more time for the NNRTI to dissociate from the RT, resulting in the resump

258 We demonstrate that changes distant from the NNRTI binding pocket decrease inhibitor binding (increas

259 of efavirenz binding extend > 60 A from the NNRTI binding pocket.

260 cooperative unfolding of a beta-sheet in the NNRTI binding pocket, which was previously observed in u

261 in the lopinavir-ritonavir group than in the NNRTI group (5.6% vs. 2.3%, P=0.16).

262 levels significantly more frequently in the NNRTI group.

263 in the lopinavir-ritonavir group than in the NNRTI group.

264 iviral activity against HIV-1, including the NNRTI-resistant Y188L mutated virus.

265 The interaction of the NNRTI nevirapine (NVP) with HIV-1 reverse transcriptase

266 (R))) and an extended release version of the NNRTI nevirapine, (Viramune XR((R))) were recent additio

267 based regimen than among those receiving the NNRTI-based regimen (1.32 vs. 2.25 episodes per person-y

268 nvolvement of binding site(s) other than the NNRTI binding pocket.

269 We show that the NNRTI binding pocket (NNIBP) is proximal to the hinge po

270 th WT RT suggested an optimal binding to the NNRTI binding pocket favoring the high anti-viral potenc

271 regions of RT heterodimer in addition to the NNRTI binding site.

272 ly 600 ns), we have captured RT bound to the NNRTI efavirenz in a closed conformation similar to that

273 e biochemical mechanism of resistance to the NNRTI nevirapine (NVP).

274 Other mutations linked to the NNRTI-resistant C181 lineage also resulted in altered NN

275 in addition to several interactions with the NNRTI binding pocket.

276 everse transcriptase (RT) genotypes with the NNRTI resistance mutations K101E+G190S are highly resist

277 articipants who initiated treatment with the NNRTI strategy, the risk of VF was significantly greater

278 The NNRTIs bind in an allosteric pocket in RT approximately

279 nucleoside RT inhibitors (NNRTI); therefore, NNRTI sensitivity was used to probe enzyme differences i

280 higher prevalence of HIV drug resistance to NNRTI in ART initiators.

281 nt HIV, potentially compromising response to NNRTI-based antiretroviral therapy (ART).

282 structures of RT(172R) and RT(172K) bound to NNRTIs or DNA/dNTP.

283 revalence of pretreatment drug resistance to NNRTIs is high.

284 ich CN and RH mutations confer resistance to NNRTIs, we hypothesized that these mutations reduce RNas

285 sociated with minority variants resistant to NNRTIs (HR, 2.6 [95% CI, 1.9-3.5]; P < .001).

286 TDR to NRTIs and PIs was <5%, whereas TDR to NNRTIs was 5%-15%.

287 e inhibitors of HIV-1 reverse transcriptase (NNRTIs).

288 orable resistance implications of PI- versus NNRTI-based first line therapy, widespread use of PI-bas

289 st likely occurs through a mechanism whereby NNRTIs stimulate priming or elongation of the tRNA.

290 rates <400 copies/ml were 8/13 (61.5%) with NNRTI-RAMs, 7/11 (63.6%) with NRTI-RAMs only, and 51/59

291 Since a major problem associated with NNRTI treatment is the emergence of drug resistant virus

292 ndomized clinical trials comparing bPI- with NNRTI-based first-line antiretroviral therapy regimens u

293 pinavir-ritonavir-based ART as compared with NNRTI-based ART reduced the incidence of malaria by 41%,

294 Combining the D549N mutant with NNRTI BP mutants further increases NNRTI resistance from

295 /=1 NNRTI-RAM, including eight patients with NNRTI-RAMs detected only by sensitive testing.

296 d 0.17 (95% CI 0.03, 1.15) for patients with NNRTI-RAMs or NRTI-RAMs only respectively vs. those with

297 d correlate the detection of resistance with NNRTI concentrations after treatment interruption and vi

298 215F/Y) were found to be highly stable, with NNRTI and PI mutations being relatively less persistent.

299 of virological failure during treatment with NNRTI-containing regimens.

300 olymerase chain reaction in subjects without NNRTI resistance by population sequencing.