ライフサイエンスコーパス: darunavir

1 z, lopinavir plus ritonavir, atazanavir, and darunavir).

2 nd 242 assigned to receive ritonavir-boosted darunavir).

3 lutegravir was superior to ritonavir-boosted darunavir.

4 in lipids observed with either atazanavir or darunavir.

5 se rate than is once-daily ritonavir-boosted darunavir.

6 tively, at the C4 position of the bis-THF of darunavir.

7 IV-2 proteases complexed with amprenavir and darunavir.

8 protease inhibitors, such as atazanavir and darunavir.

9 s for facilitating the BBB passage of an ARV darunavir.

10 increase in brain darunavir level over free darunavir.

11 9-fold higher darunavir permeation than free darunavir.

12 by concise seven-step synthesis of anti-HIV darunavir.

13 ctive concentrations, except for 1 sample of darunavir.

14 on monotherapy but retain susceptibility to darunavir.

15 intermediate-level resistance (none high) to darunavir.

16 contacts with PR than the bis-THF moiety of darunavir.

17 bserved for atazanavir and lopinavir but not darunavir.

18 binding affinity of 41 +/- 1 nM measured for darunavir.

19 actions with the protein backbone similar to darunavir (1) or inhibitor 2.

20 , 1.43-2.42), rilpivirine (1.99, 1.49-2.66), darunavir (1.62, 1.33-1.98), and efavirenz (2.12, 1.60-2

21 virine (100 mg per day) or ritonavir-boosted darunavir (100 mg ritonavir and 800 mg darunavir per day

22 ivudine (22.8%) and raltegravir plus boosted darunavir (19.8%); the most common 3DR was dolutegravir

23 gravir (229 participants), ritonavir-boosted darunavir (232), ritonavir-boosted atazanavir (231), and

24 tenofovir-lamivudine plus ritonavir-boosted darunavir ($247 per year), and urine tenofovir testing (

25 ilar between the dolutegravir (26 [11%]) and darunavir (28 [12%]) groups and between the tenofovir (2

26 More participants taking darunavir (30 [20%] participants) had drug-related adver

27 ticipants were assigned to ritonavir-boosted darunavir 400 mg and 152 continued on their lopinavir-co

28 r-generated randomisation plan, to switch to darunavir (400 mg) boosted with ritonavir (100 mg) once

29 eive either dolutegravir 50 mg once daily or darunavir 800 mg plus ritonavir 100 mg once daily, with

30 omly assigned (1:1) to dolutegravir 50 mg or darunavir 800 mg plus ritonavir 100 mg, with investigato

31 consisted of a fixed-dose tablet containing darunavir 800 mg, cobicistat 150 mg, emtricitabine 200 m

32 All subjects received darunavir 800 mg, ritonavir 100 mg, and emtricitabine 20

33 avir (50 mg once daily) or ritonavir-boosted darunavir (800 mg of darunavir plus 100 mg of ritonavir

34 NRS143) assessing the efficacy and safety of darunavir (800 mg once per day) and ritonavir (100 mg on

35 ); we recommended ritonavir (100 mg)-boosted darunavir (800 mg) once daily or ritonavir (100 mg)-boos

36 ir-boosted darunavir (ritonavir [100 mg] and darunavir [800 mg]), each administered orally once daily

37 00 mg/d; raltegravir, 400 mg twice daily; or darunavir, 800 mg/d, with ritonavir, 100 mg/d, plus comb

38 Darunavir, a potent antiviral drug, showed an unusual se

39 o[2,3-b]furan-3-ol which is a key subunit of darunavir, a widely used HIV-1 protease inhibitor drug f

40 that, in turn, was observed frequently with darunavir administration.

41 ver, drugs aliskiren (a renin inhibitor) and darunavir (an HIV-1 PR inhibitor) showed high affinity f

42 ich is one of the key structural elements of darunavir, an FDA-approved drug for the treatment of HIV

43 tenofovir-lamivudine plus ritonavir-boosted darunavir, an immediate switch would not be preferred.

44 A series of darunavir analogues featuring a substituted bis-THF ring

45 h 400 mg raltegravir twice daily plus 800 mg darunavir and 100 mg ritonavir once daily (NtRTI-sparing

46 xed-dose combination once daily, plus 800 mg darunavir and 100 mg ritonavir once daily (standard regi

47 Darunavir and darunavir + zidovudine reduced albuminuria

48 ety profile, and a superior lipid profile to darunavir and efavirenz through to 48 and 96 weeks.

49 nt with the observed second binding site for darunavir and helps to explain its antiviral potency.

50 tionalities with concurrent acylation yields darunavir and its derivatives.

51 nfected with CRF02_AG will benefit less from darunavir and nevirapine, and emtricitabine should repla

52 simple strategy to enhance brain delivery of darunavir and potentially other lipophilic ARVs for trea

53 ., 5 pM to 40 nM) in the binding affinity of darunavir and saquinavir to mature multidrug resistant p

54 ong nine clinical protease inhibitors (PIs), darunavir and saquinavir were the most effective in inhi

55 ype competitive-uncompetitive inhibition for darunavir and the chemically related amprenavir, while s

56 ciency virus type 1) protease (PR) inhibitor darunavir and the chemically related GRL98065 and GRL065

57 An alternate route for the synthesis of darunavir and three related P1 and P1' derivatives has b

58 served, all 45 sequences were susceptible to darunavir and tipranavir, whereas 47% showed resistance

59 to receive dolutegravir or ritonavir-boosted darunavir and to receive tenofovir or zidovudine; all pa

60 ltegravir, etravirine, and ritonavir-boosted darunavir) and diagnostic monitoring technologies, inclu

61 Twice-daily darunavir, once-daily darunavir, and efavirenz had the highest CSF 95% inhibit

62 The HIV-1 PIs assessed included atazanavir, darunavir, and lopinavir (administered with ritonavir).

63 lly useful susceptibility only to lopinavir, darunavir, and saquinavir.

64 orrison's equation, Ki values of amprenavir, darunavir, and tipranavir were determined to be 135, 10,

65 tenofovir-lamivudine plus ritonavir-boosted darunavir; and (3) GRT prompting switch to tenofovir-lam

66 However, all HIV-PIs, including darunavir, are generally administered with ritonavir, an

67 69 ng/mL and 74 ng/mL in the atazanavir and darunavir arms, respectively) and were not associated wi

68 rs, currently receiving boosted lopinavir or darunavir as monotherapy (n = 67) or triple antiretrovir

69 feriority of doravirine to ritonavir-boosted darunavir at 96 weeks.

70 gravir, bictegravir), 2 protease inhibitors (darunavir, atazanavir), and 2 nonnucleoside reverse tran

71 isolate showed low-level cross-resistance to darunavir, atazanavir, lopinavir, and saquinavir, but no

72 ckbone and dolutegravir or ritonavir-boosted darunavir, atazanavir, or lopinavir as the anchor drug.

73 pectrometry detection for regimens including darunavir, atazanavir, raltegravir or dolutegravir.

74 rometry detection for regimens that included darunavir, atazanavir, raltegravir, or dolutegravir.

75 Darunavir attenuated HIV and Vpr-induced activation of S

76 nofovir-emtricitabine, the ritonavir-boosted darunavir-based combination was significantly associated

77 Dolutegravir-based and darunavir-based regimens maintain good viral suppression

78 We investigated whether switch to 400 mg of darunavir boosted with 100 mg ritonavir once daily could

79 participants receiving at least one dose of darunavir boosted with ritonavir.

80 ng 96 weeks; dolutegravir is non-inferior to darunavir but is at greater risk of resistance in second

81 y of switching to a single-tablet regimen of darunavir, cobicistat, emtricitabine, and tenofovir alaf

82 how the safety and efficacy of single-tablet darunavir, cobicistat, emtricitabine, and tenofovir alaf

83 sued warnings on the use of dolutegravir and darunavir/cobicistat for treatment of pregnant women liv

84 The DIAMOND (NCT03227861) study using darunavir/cobicistat/emtricitabine/tenofovir alafenamide

85 The DIAMOND (NCT03227861) study using darunavir/cobicistat/emtricitabine/tenofovir alafenamide

86 Participants either switched immediately to darunavir/cobicistat/FTC/TAF (D/C/F/TAF) or continued IN

87 observed in the hydrophobic contacts for the darunavir complexes, in agreement with relative inhibiti

88 lative to wild type enzyme than reported for darunavir complexes.

89 Ritonavir-boosted darunavir costs $210 per year, and dolutegravir less tha

90 Pilot studies suggest that ritonavir-boosted darunavir could show high efficacy at doses below those

91 We found that darunavir does not inhibit the biochemical activity of Z

92 aily, lopinavir (LPV) 400 mg twice daily, or darunavir (DRV) 600 mg twice daily, each with ritonavir

93 n immunodeficiency virus who were exposed to darunavir (DRV) but not to atazanavir (ATV).

94 Elvitegravir (EVG), RPV, and darunavir (DRV) concentrations were quantified by the li

95 Darunavir (DRV) inhibits the replication of most existin

96 Darunavir (DRV) is exceptional among potent HIV-1 protea

97 Darunavir (DRV) is the most potent of these inhibitors,

98 trols, coadministration of OBV/PTV/r + DSV + darunavir (DRV) lowered DRV trough concentration (Ctroug

99 s often associated with amprenavir (APV) and darunavir (DRV) resistance, while the I50L substitution

100 Importantly, darunavir (DRV) was >1,000 times less active against a h

101 tion), PR(I54V), and PR(I54M) complexed with darunavir (DRV) were determined at resolutions of 1.05-1

102 crystal structures of PR(D25N) complexed to darunavir (DRV), a potent clinical inhibitor, or a non-h

103 HIV-1 protease inhibitors (PIs), such as darunavir (DRV), are the key component of antiretroviral

104 the HIV-1 PR inhibitors lopinavir (LPV) and darunavir (DRV), as well as to the broad-based inhibitor

105 re against the PR inhibitor lopinavir (LPV), darunavir (DRV), or TL-3.

106 5-7 degrees C in the presence of inhibitors darunavir (DRV), saquinavir (SQV), and lopinavir (LPV),

107 it also has weaker affinity for both NFV and darunavir (DRV).

108 en associated with reduced susceptibility to darunavir (DRV).

109 TI-R virus, they change to ritonavir-boosted darunavir (DRV/r)-based ART.

110 sted atazanavir (ATV/r) or ritonavir-boosted darunavir (DRV/r).

111 74.7%; 95% CI, 41.4%-100%; TDF+FTC+ boosted darunavir [DRV/r], 93.9%; 95% CI, 90.2%-97.7%) and lowes

112 bi), rilpivirine (RPV), or ritonavir-boosted darunavir (DRVrtv).

113 ates based on lack-of-prophylactic efficacy, darunavir, efavirenz, nevirapine, etravirine and rilpivi

114 cally active ligand alcohol was converted to darunavir efficiently.

115 Protective associations were observed for darunavir exposure (adjusted RR 0.50, 95% CI 0.24-1.00).

116 acavir, cumulative lopinavir, indinavir, and darunavir exposure was OR = 1.82 (95% CI, 1.27-2.59), OR

117 acavir, cumulative lopinavir, indinavir, and darunavir exposure was OR=1.82 (1.27-2.59), OR=2.02 (1.3

118 tenofovir-lamivudine plus ritonavir-boosted darunavir for people with dolutegravir resistance or TLD

119 scontinuation of atazanavir, raltegravir, or darunavir for toxicity.

120 regions (e.g., P1, P1', P2, and P2') of the darunavir framework have been structurally modified.

121 up (212 of 235) and in 91.7% of those in the darunavir group (210 of 229) (difference, -1.5 percentag

122 f less than 50 copies per mL than did of the darunavir group (248 [66%] of 383; difference 7.1%, 95%

123 Four (3%) patients in the darunavir group and three (2%) in the lopinavir group di

124 pants in the doravirine group and 273 in the darunavir group completed 96 weeks of treatment.

125 oup and 199 (87%) of 229 participants in the darunavir group had HIV-1 RNA less than 400 copies per m

126 nd 164 (68%) of 242 in the ritonavir-boosted darunavir group had HIV-1 RNA less than 50 copies per mL

127 e group vs 91 [24%] in the ritonavir-boosted darunavir group), nausea (45 [12%] vs 52 [14%]), headach

128 e patients in the dolutegravir group and the darunavir group.

129 nd one (<1%) of 383 in the ritonavir-boosted darunavir group.

130 ry outcome (142 [96%] of 148 participants on darunavir had <50 HIV-1 RNA copies per mL vs 143 [94%] o

131 The chemically related darunavir had similar relative inhibition, except for PR

132 Overall, inhibitor 3 compares favorably with darunavir in affinity for PR20 and shows promise for fur

133 he two new compounds are more effective than darunavir in inhibiting mature PR20 and show promise for

134 hether a new and chemically distinct HIV-PI, darunavir, inhibits ZMPSTE24.

135 Darunavir is a potent HIV protease inhibitor that has be

136 This property of darunavir is potentially attractive.

137 TMC114 (darunavir) is a promising clinical inhibitor of HIV-1 pr

138 to achieve 3.38-5.93-fold increase in brain darunavir level over free darunavir.

139 the hydroxy group of the bound clinical drug darunavir, located in the catalytic site of enzyme HIV-1

140 suggests that canagliflozin, aliskiren, and darunavir may induce profound effects toward dual HIV-1

141 Low-dose ritonavir-boosted darunavir might be a safe and efficacious switch option

142 ions, and the mutation profiles suggest that darunavir might be the drug of choice for third-line reg

143 er dolutegravir (n=235) or ritonavir-boosted darunavir (n=229) and to receive lamivudine plus either

144 d to doravirine (n=385) or ritonavir-boosted darunavir (n=384), and 383 in both groups were given at

145 were synthesized by incorporating bis-THF of darunavir on either side of the Phe-Phe isostere of lopi

146 rate than did those taking ritonavir-boosted darunavir once daily, with similar tolerability.

147 Twice-daily darunavir, once-daily darunavir, and efavirenz had the h

148 ilpivirine) or a boosted protease inhibitor (darunavir or atazanavir).

149 previr had no clinically relevant effects on darunavir or tenofovir PK (15% and 22% AUC increase, res

150 ir-boosted protease inhibitor (atazanavir or darunavir), or an integrase strand transfer inhibitor (r

151 ith dolutegravir, elvitegravir, rilpivirine, darunavir, or efavirenz as the third drug.

152 andomized to ritonavir-boosted atazanavir or darunavir, or raltegravir-based cART.

153 onavir-boosted atazanavir, ritonavir-boosted darunavir, or raltegravir.

154 Patients being treated with darunavir, or who had homozygous familial hypercholester

155 alafenamide/emtricitabine plus dolutegravir; darunavir; or both) during primary HIV infection were en

156 transaminase in three (1%; one symptomatic) darunavir participants led to study withdrawal; all tran

157 g 5-15% DHA were 90-140 nm in size, had high darunavir payload (~11-13% w/w), good stability and mini

158 BBB permeation and brain accumulation of the darunavir payload.

159 osted darunavir (100 mg ritonavir and 800 mg darunavir per day), both with investigator-selected nucl

160 anocarrier uptake and up to 8.99-fold higher darunavir permeation than free darunavir.

161 y) or ritonavir-boosted darunavir (800 mg of darunavir plus 100 mg of ritonavir once daily) in combin

162 inhibitors (DRV/r+2NRTIs), ritonavir-boosted darunavir plus dolutegravir (DTG+DRV/r), or dolutegravir

163 avir plus raltegravir; B2, ritonavir-boosted darunavir plus raltegravir plus etravirine; B3, ritonavi

164 fovir plus lamivudine), C (ritonavir-boosted darunavir plus raltegravir plus tenofovir-emtricitabine

165 (best available NRTIs plus ritonavir-boosted darunavir plus raltegravir) were defined by increasing l

166 se inhibitors [NRTIs] plus ritonavir-boosted darunavir plus raltegravir; B2, ritonavir-boosted daruna

167 e (DOR) demonstrated noninferior efficacy to darunavir plus ritonavir (DRV+r) and efavirenz (EFV) in

168 g) arms from these trials were compared with darunavir plus ritonavir (DRV+r) in DRIVE-FORWARD and ef

169 r dolutegravir (four [2%] patients) than for darunavir plus ritonavir (ten [4%] patients) and contrib

170 diarrhoea (dolutegravir 41 [17%] patients vs darunavir plus ritonavir 70 [29%] patients), nausea (39

171 the dolutegravir group and 13 (four) in the darunavir plus ritonavir group discontinued because of a

172 he dolutegravir group vs 57/242 [24%] in the darunavir plus ritonavir group), nausea (31/242 [13%] vs

173 olutegravir and 200 (83%) patients receiving darunavir plus ritonavir had HIV-1 RNA of less than 50 c

174 In FLAMINGO, we compared dolutegravir with darunavir plus ritonavir in individuals naive for antire

175 aily dolutegravir was superior to once-daily darunavir plus ritonavir.

176 ns were switched to one of ritonavir-boosted darunavir plus two nucleoside reverse transcriptase inhi

177 ined similar interactions as observed in the darunavir-protease complex regardless of the position on

178 These data demonstrate that darunavir protects against HIV-induced renal injury via

179 s was susceptibility to etravirine (78%) and darunavir/r (97%).

180 ravir plus etravirine; B3, ritonavir-boosted darunavir, raltegravir, and either tenofovir plus emtric

181 ibitor) used from 2013 to 2018: rilpivirine, darunavir, raltegravir, elvitegravir, dolutegravir, efav

182 vourably in efficacy and safety to a boosted darunavir regimen with nucleoside reverse transcriptase

183 %) had previous virological failure on a non-darunavir regimen.

184 ration of atazanavir (300 mg once daily) and darunavir regimens exhibited no clinically meaningful dr

185 with a history of virological failure on non-darunavir regimens were allowed.

186 e coadministered with morning atazanavir and darunavir regimens.

187 gravir resistance; no participants developed darunavir resistance (p=0.0023).

188 No darunavir resistance was observed.

189 An extremely darunavir-resistant mutant precursor is more responsive

190 ation than raltegravir and ritonavir-boosted darunavir, respectively, primarily because of hyperbilir

191 d doravirine (100 mg) with ritonavir-boosted darunavir (ritonavir [100 mg] and darunavir [800 mg]), e

192 (TDF/FTC) plus atazanavir-ritonavir (ATV/r), darunavir-ritonavir (DRV/r), or raltegravir (RAL) in ACT

193 ency virus (HIV)-negative volunteers (11 for darunavir-ritonavir and 10 for fosamprenavir-ritonavir)

194 e buprenorphine-3-glucuronide suggested that darunavir-ritonavir and fosamprenavir-ritonavir induced

195 anagement, and the protease inhibitors (PIs) darunavir-ritonavir and fosamprenavir-ritonavir.

196 ikely to be necessary when buprenorphine and darunavir-ritonavir or fosamprenavir-ritonavir are coadm

197 non-opioid-dependent volunteers who received darunavir-ritonavir or fosamprenavir-ritonavir but not b

198 zanavir-ritonavir, 185 in those who received darunavir-ritonavir, 243 in those who received rilpiviri

199 Patients received darunavir-ritonavir, 600/100 mg twice daily, plus an inv

200 included dolutegravir, atazanavir-ritonavir, darunavir-ritonavir, oral rilpivirine, raltegravir, or e

201 udies, healthy adult volunteers received (1) darunavir/ritonavir (800 mg/100 mg once daily) with and

202 < 50 copies/mL during >/=6 months on stable darunavir/ritonavir (800/100 mg once daily) or lopinavir

203 were susceptibility to etravirine (78%) and darunavir/ritonavir (97%).

204 (TDF/FTC) plus atazanavir/ritonavir (ATV/r), darunavir/ritonavir (DRV/r), or RAL.

205 (TDF/FTC) plus atazanavir/ritonavir (ATV/r), darunavir/ritonavir (DRV/r), or raltegravir (RAL).

206 rse transcriptase inhibitors associated with darunavir/ritonavir (n = 12), saquinavir/ritonavir (n =

207 st when combined with dolutegravir (n = 18), darunavir/ritonavir (n = 34), or lopinavir/ritonavir (n

208 signed to atazanavir/ritonavir 300/100 mg or darunavir/ritonavir 800/100 mg in combination with tenof

209 or 6 months or longer on triple therapy with darunavir/ritonavir and 2 nucleos(t)ides (tenofovir diso

210 Of 46 subjects enrolled, 56% received darunavir/ritonavir and 44% lopinavir/ritonavir.

211 d to continue therapy (n = 128) or switch to darunavir/ritonavir and lamivudine (n = 129).

212 rapeutic noninferiority of dual therapy with darunavir/ritonavir and lamivudine compared to triple th

213 Dual therapy with darunavir/ritonavir and lamivudine demonstrated noninfer

214 more in the atazanavir/ritonavir arm than in darunavir/ritonavir arm.

215 nucleoside reverse-transcriptase inhibitors+darunavir/ritonavir at week-48.

216 nued atazanavir/ritonavir and 5 discontinued darunavir/ritonavir due to adverse effects.

217 olled study, individuals taking dolutegravir+darunavir/ritonavir had greater increases in systolic an

218 differences between atazanavir/ritonavir and darunavir/ritonavir in efficacy, clinically relevant sid

219 ctions were observed between faldaprevir and darunavir/ritonavir or tenofovir.

220 , 56 (62%) atazanavir/ritonavir and 62 (71%) darunavir/ritonavir patients remained free of treatment

221 d 71 (79%) atazanavir/ritonavir and 75 (85%) darunavir/ritonavir patients remained free of virologica

222 d lamivudine compared to triple therapy with darunavir/ritonavir plus 2 nucleos(t)ides for maintenanc

223 previr and the commonly used antiretrovirals darunavir/ritonavir, efavirenz, and tenofovir to guide t

224 tegravir, rilpivirine, atazanavir/ritonavir, darunavir/ritonavir, lopinavir/ritonavir, or efavirenz/e

225 on, plus dolutegravir, atazanavir/ritonavir, darunavir/ritonavir, or lopinavir/ritonavir.

226 ate/emtricitabine plus atazanavir/ritonavir, darunavir/ritonavir, or raltegravir (RAL).

227 ate/emtricitabine plus atazanavir/ritonavir, darunavir/ritonavir, or raltegravir among treatment-naiv

228 to first-line regimens containing efavirenz, darunavir/ritonavir, or raltegravir regardless of pretre

229 ricitabine plus either atazanavir/ritonavir, darunavir/ritonavir, or raltegravir.

230 l of 53.4% showed intermediate resistance to darunavir/ritonavir, whereas high-level resistance was n

231 des and more total and subcutaneous fat than darunavir/ritonavir.

232 RNA-seq analyses demonstrated that darunavir suppressed HIV-induced upregulation of immune

233 mine whether dolutegravir is non-inferior to darunavir, the best-in-class protease inhibitor drug, an

234 target" cellular effects, we studied whether darunavir, the most commonly prescribed protease inhibit

235 IV-2 proteases complexed with amprenavir and darunavir to models of the PRDelta4 enzyme.

236 t aldol adduct introduces the P1 fragment of darunavir via an aldehyde.

237 ificantly higher anti-HIV activity than free darunavir (viral titer 2 to 2.6-fold higher in latter gr

238 Ritonavir-boosted darunavir was also effective.

239 At week 48, darunavir was non-inferior to lopinavir for the primary

240 4.8 to 14.5; P<0.001), but ritonavir-boosted darunavir was not (adjusted difference, 5.6 percentage p

241 efficacy and tolerability, ritonavir-boosted darunavir was superior to ritonavir-boosted atazanavir,

242 containing raltegravir or ritonavir-boosted darunavir was superior to that of the ritonavir-boosted

243 hibitors including the highly important drug darunavir, was achieved via a one-pot procedure using fu

244 Raltegravir and ritonavir-boosted darunavir were equivalent for tolerability, whereas rito

245 Switching from darunavir, White race, total to high-density lipoprotein

246 ical trial, which compared ritonavir-boosted darunavir with either raltegravir or tenofovir disoproxi

247 of ART (84 participants on ritonavir-boosted darunavir with raltegravir and 84 participants on ritona

248 vir and 84 participants on ritonavir-boosted darunavir with tenofovir disoproxil fumarate and emtrici

249 n non-inferior efficacy to ritonavir-boosted darunavir, with a superior lipid profile, in adults with

250 are, that dolutegravir and ritonavir-boosted darunavir would each be superior to ritonavir-boosted lo

251 Darunavir and darunavir + zidovudine reduced albuminuria and histologi

252 ice were treated with darunavir, zidovudine, darunavir + zidovudine, or control.

253 Mice were treated with darunavir, zidovudine, darunavir + zidovudine, or contro