ライフサイエンスコーパス: raltegravir

1 , or an integrase strand transfer inhibitor (raltegravir).

2 repeated passage in the presence of 200 muM raltegravir.

3 r, emtricitabine, efavirenz, atazanavir, and raltegravir.

4 , severe adverse event during treatment with raltegravir.

5 ing, suggesting a common mode of action with raltegravir.

6 o the target of integrase inhibitors such as raltegravir.

7 T) and tenofovir and the integrase inhibitor raltegravir.

8 tients failing treatment regimens containing raltegravir.

9 bjects failing treatment regimens containing raltegravir.

10 vely greater resistance to elvitegravir than raltegravir.

11 tazanavir/ritonavir, darunavir/ritonavir, or raltegravir.

12 mtricitabine with efavirenz, rilpivirine, or raltegravir.

13 here was no advantage to replacing them with raltegravir.

14 ogic failure was rare but more frequent with raltegravir.

15 Administration (US FDA) approved MK-0518, or raltegravir ( 1), as the first IN inhibitor for HIV/AIDS

16 roM), L-731,988 (34 nM), L-870,810 (2.4 nM), raltegravir (10 nM), elvitegravir (4.0 nM), and GSK36473

17 interactive voice and web response system to raltegravir 1200 mg (two 600 mg tablets) orally once dai

18 These results support the use of raltegravir 1200 mg once daily for first-line therapy.

19 INTERPRETATION: A once daily raltegravir 1200 mg regimen was non-inferior compared wi

20 allocated to treatment, of whom 281 received raltegravir, 282 received efavirenz, and three were neve

21 130 nM vs 9 nM), L-870,810 (130 nM vs 4 nM), raltegravir (300 nM vs 9 nM), elvitegravir (90 nM vs 6 n

22 mg (two 600 mg tablets) orally once daily or raltegravir 400 mg (one tablet) orally twice daily, each

23 ery 8 hours for 9 days plus a single dose of raltegravir 400 mg on day 10 followed by a washout perio

24 wed by a washout period and a single dose of raltegravir 400 mg on day 38, or the same medication in

25 00 mg regimen was non-inferior compared with raltegravir 400 mg twice daily for initial treatment of

26 >/=1 year were randomly assigned to receive raltegravir 400 mg twice daily or placebo for 24 weeks.

27 Patients were randomly assigned (2:1) to raltegravir 400 mg twice daily or placebo, both with opt

28 udy in HIV-infected pregnant women receiving raltegravir 400 mg twice daily was performed (Pharmacoki

29 ession for >/= 1 year were randomized to add raltegravir (400 mg twice daily) or matching placebo for

30 ratio to switch from lopinavir-ritonavir to raltegravir (400 mg twice daily; n=353) or to remain on

31 ritonavir (100 mg once per day) plus either raltegravir (400 mg twice per day; NtRTI-sparing regimen

32 or plus NRTI group), protease inhibitor plus raltegravir (400 mg twice per day; protease inhibitor pl

33 zanavir, 300 mg/d, with ritonavir, 100 mg/d; raltegravir, 400 mg twice daily; or darunavir, 800 mg/d,

34 er inhibitor (dolutegravir, elvitegravir, or raltegravir), a nonnucleoside reverse transcriptase inhi

35 Similarly, raltegravir, a pharmacologic integrase inhibitor, abolis

36 Previous reports showed that raltegravir, a recently approved antiviral compound that

37 The end-stage LIVER disease and RALtegravir-Agence Nationale de Recherche sur le Sida et

38 ); each PI had greater increases relative to raltegravir (all P </= .001 at week 96).

39 ) and C(max) for raltegravir + boceprevir vs raltegravir alone were 1.04 (90% CI, .88-1.22) and 1.11

40 ion (C(max)) for raltegravir + boceprevir vs raltegravir alone were 4.27 (95% confidence interval [CI

41 drug-drug interaction between boceprevir and raltegravir, an HIV integrase inhibitor.

42 RK-2-investigated the efficacy and safety of raltegravir, an HIV-1 integrase strand-transfer inhibito

43 the limits of quantification at 1 pg/mL for raltegravir and 2 pg/mL for four proprietary compounds.

44 462 were treated with raltegravir and 237 with placebo.

45 viral intensification therapy (standard dose raltegravir and dose-adjusted maraviroc based on baselin

46 Raltegravir and efavirenz-based initial antiretroviral t

47 ns that determine the resistance pathways to raltegravir and elvitegravir (N155H, Q148K/R/H, and E92Q

48 grase inhibitors are in clinical trials, and raltegravir and elvitegravir are likely to be the first

49 Our findings demonstrate that both raltegravir and elvitegravir are potent IN inhibitors an

50 rugs with IN, consistent with the binding of raltegravir and elvitegravir at the IN-DNA interface.

51 (3) to determine the resistance profile for raltegravir and elvitegravir in those IN mutants.

52 1) to investigate and compare the effects of raltegravir and elvitegravir on the three IN-mediated re

53 ts harboring resistance to the other INSTIs, raltegravir and elvitegravir.

54 sted lopinavir, and the integrase inhibitors raltegravir and elvitegravir.

55 fect of pregnancy on the pharmacokinetics of raltegravir and its safety and efficacy in HIV-infected

56 (42%) of all patients initially assigned to raltegravir and less than 400 copies per mL in 210 (45%)

57 703 randomized patients (462 and 237 in the raltegravir and placebo groups, respectively) received t

58 g-related adverse events were similar in the raltegravir and placebo groups.

59 going close to those of the clinically used raltegravir and retained potencies against a panel of IN

60 Raltegravir and ritonavir-boosted darunavir were equival

61 cidence of tolerability discontinuation than raltegravir and ritonavir-boosted darunavir, respectivel

62 l modeling to visualize interactions between raltegravir and the imputed HLA molecule.

63 nt resistance to APV, an integrase inhibitor raltegravir, and a GRL-09510 congener (GRL-09610), no va

64 arious levels of resistance to dolutegravir, raltegravir, and elvitegravir.

65 l use of recently approved drugs (maraviroc, raltegravir, and etravirine) in treatment-experienced pa

66 rd prophylaxis, adjunctive raltegravir or no raltegravir, and supplementary food or no supplementary

67 L54 mutant viruses were fully susceptible to raltegravir, any virus bearing the UL42 mutation was as

68 The geometric mean (GM) of raltegravir area under the concentration-time curve (AUC

69 Raltegravir as a film-coated tablet 400 mg twice daily (

70 recommend a boosted protease inhibitor plus raltegravir as an alternative second-line combination.

71 earing the UL42 mutation was as resistant to raltegravir as clone 7.

72 gions to evaluate the safety and efficacy of raltegravir, as compared with placebo, in combination wi

73 GM ratio estimates of raltegravir AUC(0-12h) and C(max) for raltegravir + boce

74 itonavir-boosted atazanavir or darunavir, or raltegravir-based cART.

75 Raltegravir-based combination treatment had rapid and po

76 A raltegravir-based regimen was associated with significan

77 prior peg-IFN/RBV standard therapy and on a raltegravir-based regimen with HIV RNA <400 copies/mL.

78 ed antiretroviral therapy (ART) regimen to a raltegravir-based regimen.

79 In 2007, raltegravir became the first integrase inhibitor approve

80 references of HIV integrase and to (2) study raltegravir binding in the context of these dynamic mode

81 Raltegravir binds to IN and blocks the integration of th

82 tes of raltegravir AUC(0-12h) and C(max) for raltegravir + boceprevir vs raltegravir alone were 1.04

83 nd maximum plasma concentration (C(max)) for raltegravir + boceprevir vs raltegravir alone were 4.27

84 Elvitegravir was more potent than raltegravir, but neither drug could block disintegration

85 f a clinically significant drug interaction, raltegravir can be recommended for combined HIV/HCV trea

86 Raltegravir can be used in standard dosages in HIV-infec

87 A total of 21 different raltegravir-chelator derivative (RCD) compounds were pre

88 RT recipients, IHS was associated with lower raltegravir concentrations in blood and semen, compared

89 ents before and 48 weeks after initiation of raltegravir-containing combination antiretroviral therap

90 V-1-infected patients, who started a salvage raltegravir-containing regimen, were investigated.

91 tients who are not consistent in following a raltegravir-containing treatment regimen.

92 The median ratio of raltegravir cord to maternal blood was 1.21 (interquarti

93 lipid changes noted with the PIs relative to raltegravir deserves further evaluation.

94 he primary analysis, protease inhibitor plus raltegravir did not meet non-inferiority criteria.

95 At low nanomolar concentrations (<50 nM), raltegravir displayed a time-dependent inhibition of con

96 Results of the study indicate that raltegravir displayed linear pharmacokinetics between a

97 patients were included, of which 68% started raltegravir during pregnancy.

98 The observed mean decrease in exposure to raltegravir during third trimester compared to postpartu

99 combination of tenofovir, emtricitabine, and raltegravir effectively suppresses peripheral and system

100 The results show raltegravir, elvitegravir, MK-2048, RDS 1997, and RDS 21

101 rformed on plasma samples at baseline and at raltegravir failure.

102 We compared substitution of raltegravir for lopinavir-ritonavir with continuation of

103 fety, tolerability, and efficacy of multiple raltegravir formulations in human immunodeficiency virus

104 Emergent resistance was associated with the raltegravir group (OR 2.47, 95% CI 1.02-5.99; p=0.05), b

105 (81%) of 383 in the protease inhibitor plus raltegravir group (p=0.07; lower 95% confidence limit fo

106 roup, 64% of the patients (mean, 277) in the raltegravir group (P=0.21 for the comparison with the NR

107 6% of patients in the NRTI group, 86% in the raltegravir group (P=0.97), and 61% in the monotherapy g

108 viral load measurements at 96 weeks; in the raltegravir group 236 had baseline sequence data and 255

109 l failure was 10.3% (95% CI 6.5-14.0) in the raltegravir group and 12.4% (8.3-16.5) in the NRTI group

110 ndomly assigned 515 participants: 260 to the raltegravir group and 255 to the NRTI group; two partici

111 After week 156, 251 patients (54%) from the raltegravir group and 47 (20%) from the placebo group en

112 ticipants had virological failure (46 in the raltegravir group and 50 in the NRTI group).

113 62 (24%) participants in the raltegravir group and 81 (32%) in the NRTI group had gra

114 e) showed that 86.1% (n=241 patients) of the raltegravir group and 81.9% (n=230) of the efavirenz gro

115 5 to the NRTI group; two participants in the raltegravir group and one in the NRTI group were exclude

116 f 383 patients in the protease inhibitor and raltegravir group at week 144 (p=0.02) and 233 (61%) of

117 er than expected virological efficacy in the raltegravir group compared with the lopinavir-ritonavir

118 The raltegravir group had a significant increase in the leve

119 4%, 95% CI 80.2-88.1) of 347 patients in the raltegravir group had vRNA concentration less than 50 co

120 were significantly greater (p<0.0001) in the raltegravir group than in the lopinavir-ritonavir group

121 At week 156, 51% in the raltegravir group versus 22% in the placebo group (non-c

122 inavir) plus 400 mg raltegravir twice a day (raltegravir group) or to ritonavir-boosted lopinavir plu

123 00 mg twice per day; protease inhibitor plus raltegravir group), or protease inhibitor monotherapy (p

124 lus raltegravir in a superiority comparison (raltegravir group, 433 patients), or protease-inhibitor

125 -ritonavir group (3%) and no patients in the raltegravir group.

126 in the NtRTI group and 3.0 (1.0-4.3) in the raltegravir group.

127 cluded in the NtRTI group and and 270 in the raltegravir group.

128 ritonavir-boosted lopinavir and raltegravir (raltegravir-group) provided non-inferior efficacy to rit

129 Raltegravir has a favourable long-term efficacy and safe

130 ce susceptibility to the integrase inhibitor raltegravir have been identified in patients failing tre

131 t clinical trials of the integrase inhibitor raltegravir have demonstrated more rapid viral decay tha

132 apy after 12 weeks of induction therapy with raltegravir in a noninferiority comparison (monotherapy

133 up, 426 patients), a protease inhibitor plus raltegravir in a superiority comparison (raltegravir gro

134 at was intensified (iART) with maraviroc and raltegravir in an open-label fashion.

135 The use of raltegravir in human immunodeficiency virus (HIV)-infect

136 Resistance to raltegravir in integrase strand transfer inhibitor-naive

137 pressed while taking a stable atazanavir- or raltegravir-inclusive antiretroviral regimen.

138 tients previously reported to have developed raltegravir-induced DRESS syndrome and in 1 previously u

139 Five of the 6 patients who developed raltegravir-induced DRESS syndrome were African, and 1 w

140 tween carriage of the HLA-B*53:01 allele and raltegravir-induced DRESS syndrome, and the potential ut

141 ele HLA-B*53:01 in the immunopathogenesis of raltegravir-induced DRESS syndrome.

142 up), or protease inhibitor monotherapy (plus raltegravir induction for first 12 weeks, re-intensified

143 blotting and quantitative PCR revealed that raltegravir inhibits DNA replication of HSV-1 rather tha

144 Raltegravir intensification did not have a significant e

145 , placebo-controlled study to assess whether raltegravir intensification reduces low-level viral repl

146 Raltegravir intensification resulted in a rapid increase

147 Raltegravir is a recently, Food and Drug Administration-

148 Raltegravir is a well tolerated alternative to efavirenz

149 Raltegravir is an alternative for treatment-experienced

150 Ritonavir-boosted lopinavir plus raltegravir is an appropriate alternative, especially if

151 Raltegravir is an FDA approved inhibitor directed agains

152 , and MK-0536 are equally effective, whereas raltegravir is approximately 70% as effective.

153 b to autoimmune disease, are not affected by raltegravir, lupus-prone (NZBxNZW) F(1) mice die of glom

154 Overall, these results suggest that raltegravir may be a valuable therapeutic agent against

155 re, the anti-HIV-1 drugs AZT, tenofovir, and raltegravir may be useful for treatment of XMRV infectio

156 ntly unknown, virtual modeling suggests that raltegravir may bind within the antigen binding cleft of

157 Removing the NRTIs or replacing them with raltegravir may provide a benefit.

158 se of antiviral agents (i.e., zidovudine and raltegravir) may be of benefit.

159 tion, previously identified with MK-2048 and raltegravir, may represent the initial substitution in a

160 Raltegravir (MK-0518) is an inhibitor of human immunodef

161 target of the newly approved anti-AIDS drug raltegravir (MK-0518, Isentress) while elvitegravir (GS-

162 nical adverse events occurred in patients on raltegravir (n=124 [44.1%]) than those on efavirenz (n=2

163 and safety analyses for the combined trials (raltegravir, n=350; lopinavir-ritonavir, n=352).

164 mparison with the NRTI group; superiority of raltegravir not shown), and 55% of the patients (mean, 2

165 INTERPRETATION: Protease inhibitor plus raltegravir offered no advantage over protease inhibitor

166 We report here that the activity profile of raltegravir on the replication of murine leukemia virus

167 virus specifically blocked at integration by raltegravir or catalytic site mutations (IN(D64N/D116N/E

168 atients, 471 patients had viruses with >/= 1 raltegravir or elvitegravir resistance mutation (15.6%).

169 le continuing their failing regimen (without raltegravir or elvitegravir) through day 7, after which

170 east 1 ritonavir-boosted protease inhibitor, raltegravir or etravirine.

171 phylaxis or standard prophylaxis, adjunctive raltegravir or no raltegravir, and supplementary food or

172 Patients were randomly assigned to raltegravir or placebo in a 2:1 ratio.

173 Tolerability of regimens containing raltegravir or ritonavir-boosted darunavir was superior

174 ed resting CD4(+) T cells in the presence of raltegravir or with integrase active-site mutant HIV-1 y

175 e, defined as discontinuation of atazanavir, raltegravir, or darunavir for toxicity.

176 stance was predicted in 12% of patients with raltegravir- or elvitegravir-resistant viruses (2% of al

177 lected, without resistance testing); or with raltegravir; or alone as protease inhibitor monotherapy

178 ted patients with limited treatment options, raltegravir plus optimized background therapy provided b

179 Raltegravir produced the most favorable lipid profile.

180 Merck's Raltegravir (RAL) (October 2007) and Gilead's Elvitegrav

181 were evaluated here for susceptibilities to raltegravir (RAL) and elvitegravir (EVG).

182 tegrase strand transfer inhibitors (INSTIs), raltegravir (RAL) and elvitegravir (EVG).

183 e inhibitor, has limited cross-resistance to raltegravir (RAL) and elvitegravir in vitro.

184 protease inhibitor (PI) regimen, a switch to raltegravir (RAL) can be an option in case of comorbidit

185 (RIF) induces UGT1A1, an enzyme involved in raltegravir (RAL) elimination, thereby potentially lower

186 vir (ATV/r), darunavir-ritonavir (DRV/r), or raltegravir (RAL) in ACTG A5260s, a substudy of A5257.

187 efficacy, and pharmacokinetic parameters of raltegravir (RAL) in human immunodeficiency virus (HIV)-

188 antiretroviral therapy (cART) incorporating raltegravir (RAL) is highly effective for virologic supp

189 d the effect of switching efavirenz (EFV) to raltegravir (RAL) on hepatic steatosis among HIV-infecte

190 t is unclear whether the integrase inhibitor raltegravir (RAL) reduces inflammation and immune activa

191 ave shown that all three FDA-approved drugs, raltegravir (RAL), elvitegravir and dolutegravir (DTG),

192 In the presence of raltegravir (RAL), MK-2048, and L-841,411, IN incorporat

193 Resistance to raltegravir (RAL), the first HIV-1 integrase (IN) inhibi

194 to define viral kinetics after initiation of raltegravir (RAL)-based antiretroviral therapy (ART).

195 mary resistance pathways in subjects failing raltegravir (RAL)-containing treatments.

196 ure frequently lead to cross-resistance with raltegravir (RAL).

197 vir (ATV/r), darunavir/ritonavir (DRV/r), or raltegravir (RAL).

198 -G140S/Q148H mutant virus in the presence of raltegravir (RAL); the RT-K103N mutation had no effect.

199 [LPV/r], 71.1%; 95% CI, 43.6%-98.6%; TDF+FTC+raltegravir [RAL], 74.7%; 95% CI, 41.4%-100%; TDF+FTC+ b

200 ing ART with ritonavir-boosted lopinavir and raltegravir (raltegravir-group) provided non-inferior ef

201 when compared to an abbreviated analogue of raltegravir (RCD-1).

202 patients experiencing virological failure to raltegravir received dolutegravir with optimized backgro

203 ent in 13 of these 17 patients: 7 of the 462 raltegravir recipients (1.5%) and 6 of the 237 placebo r

204 Virological failure occurred in 166 raltegravir recipients (36%) during the double-blind pha

205 ncompletion as treatment failure, 355 of 458 raltegravir recipients (77.5%) had HIV-1 RNA levels belo

206 follow-up, cancers were detected in 3.5% of raltegravir recipients and in 1.7% of placebo recipients

207 iter was achieved at week 16 in 61.8% of the raltegravir recipients, as compared with 34.7% of placeb

208 ontaining efavirenz, darunavir/ritonavir, or raltegravir regardless of pretreatment viral load.

209 ause mortality among 415 patients starting a raltegravir regimen compared to 2646 starting an efavire

210 c pathways to resistance in subjects failing raltegravir regimens and defines the effects of primary

211 and the recombinant viruses were tested for raltegravir resistance.

212 IN inhibitors, and may help overcome rising raltegravir resistance.

213 Extended antiviral testing against a few raltegravir-resistant HIV-1 clones revealed a resistance

214 A raltegravir-resistant HSV-1 mutant was generated by repe

215 8 is equally potent against wild-type IN and raltegravir-resistant IN mutant N155H, suggesting this i

216 Studies of raltegravir-resistant IN mutants N155H and Q148H without

217 l loads of 42 raltegravir-susceptible and 40 raltegravir-resistant specimens were determined using Re

218 The dynamics of raltegravir-resistant variants and their impact on virol

219 g that the RealTime HIV-1 assay can tolerate raltegravir-selected mutations.

220 The pharmacokinetics of raltegravir showed extensive variability.

221 ese important questions, we investigated the raltegravir susceptibility and replication capacity of v

222 rimary and secondary resistance mutations on raltegravir susceptibility and replication capacity.

223 y mutations and other secondary mutations on raltegravir susceptibility and viral replication capacit

224 ion generally displayed larger reductions in raltegravir susceptibility than viruses with an N155H mu

225 Viral loads of 42 raltegravir-susceptible and 40 raltegravir-resistant spe

226 resulted in a higher level of resistance to raltegravir than N155H alone.

227 of Q148H showed a higher cross-resistance to raltegravir than observed with N155H, providing evidence

228 iral suppression was shorter for patients on raltegravir than on efavirenz (log-rank test p<0.0001).

229 ing G140S and Q148K were more susceptible to raltegravir than viruses containing a Q148K mutation alo

230 with a G140S mutation were more resistant to raltegravir than viruses containing a Q148R(H) mutation

231 This paper shows that raltegravir, the antiretrovirus drug targeting integrase

232 results did not establish non-inferiority of raltegravir to lopinavir-ritonavir.

233 We compared a new once daily formulation of raltegravir to the currently marketed twice daily formul

234 Raltegravir-treated NZB mice, which share the H-2 haplot

235 he potential utility of HLA screening before raltegravir treatment.

236 mg ritonavir, 400 mg lopinavir) plus 400 mg raltegravir twice a day (raltegravir group) or to ritona

237 f ritonavir once daily), each with 400 mg of raltegravir twice daily and 300 mg of tenofovir disoprox

238 ratio (double-blind) to receive 400 mg oral raltegravir twice daily or 600 mg oral efavirenz once da

239 ratio to receive oral treatment with 400 mg raltegravir twice daily plus 800 mg darunavir and 100 mg

240 r which all patients were offered open-label raltegravir until week 240.

241 The discovery of raltegravir validated the existence of the IN, which is

242 ratio was 5.7-fold higher (P = .023) in the raltegravir vs. placebo group.

243 Although switching to raltegravir was associated with greater reductions in se

244 Exposure to raltegravir was highly variable.

245 ence of -3.4% (-8.4 to 1.5), indicating that raltegravir was non-inferior, but not superior, to NRTIs

246 uperior to ritonavir-boosted atazanavir, and raltegravir was superior to both protease inhibitors.

247 Raltegravir was well tolerated during pregnancy.

248 cause nonautoimmune mice are not affected by raltegravir, we consider off-target effects unlikely and

249 ed after treatment with a suboptimal dose of raltegravir were aberrant.

250 In this study, subtoxic levels of raltegravir were shown to inhibit the replication of fou

251 We compared the safety and efficacy of raltegravir with efavirenz as part of combination antire

252 Use of raltegravir with optimum background therapy is effective

253 med to assess whether boosted lopinavir plus raltegravir would be non-inferior to boosted lopinavir p