400 Tablets 400 mg 025286 800 Tablets 800 mg 026221
1 PREZISTA ritonavir PREZISTA /rtv HIV-1 40 8.4 14 2 2.1 PREZISTA /ritonavir / HIV-1 12.4 2.3 2.4 2.5 PREZISTA /ritonavir 5.2 2.2 PREZISTA /ritonavir 酶 1
PREZISTA /ritonavir 5.2 2.3 PREZISTA ritonavir PREZISTA ritonavir darunavir PREZISTA 800 1 800 2 400 ritonavir 100 treatment-experienced treatment-experienced PREZISTA 2
600 ritonavir 100 PREZISTA 600 treatment-experienced PREZISTA /ritonavir PREZISTA ritonavir darunavir * PREZISTA 800 1 800 2 400 ritonavir 100 / darunavir * PREZISTA 600 ritonavir 100 / PREZISTA 600 * V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V L89V 3
2.4 PREZISTA 600 ritonavir 100 PREZISTA 800 ritonavir 100 PREZISTA 800 ritonavir 100 HIV-1 RNA 50 copies/ml PREZISTA 600 ritonavir 100 2.5 PREZISTA /ritonavir PREZISTA /ritonavir 8.4 12.3 treatment-experienced 4
darunavir * 40 PREZISTA 800 1 800 2 400 ritonavir 100 * Darunavir V11I, V32I, L33F, I47V, I50V, I54M, I54L, T74P, L76V, I84V L89V treatment-experienced darunavir * 40 PREZISTA 600 ritonavir 100 PREZISTA 600 * Darunavir V11I, V32I, L33F, I47V, I50V, I54M, I54L, T74P, L76V, I84V L89V PREZISTA /ritonavir 3 5.10 8.4 5
2.6 PREZISTA /rtv PREZISTA /rtv 8.6 12.3 3 PREZISTA 400 400 darunavir darunavir ethanolate 400 TMC 800 800 darunavir darunavir ethanolate 800 T 4 PREZISTA /rtv CYP3A / 6
darunavir 1 7.3 PREZISTA ritonavir ritonavir ritonavir 1 PREZISTA /rtv PREZISTA /rtv Alpha 1- alfuzosin / ranolazine / 7
dronedarone / colchicine / / rifampin Rifampin CYP450 PREZISTA /rtv rifampin darunavir PREZISTA lurasidone / pimozide / 8
dihydroergotamine ergotamine methylergonovine / cisapride / / midazolam triazolam Triazolam midazolam CYP3A triazolam midazolam PREZISTA /rtv benzodiazepine / 9
C HMG-CoA 酶 St. John's wort elbasvir/grazoprevir lovastatin simvastatin PREZISTA /rtv St. John's wort darunavir PREZISTA 酶 ALT atorvastatin pravastatin rosuvastatin 6 10
PDE-5 sildenafil PREZISTA /rtv sildenafil 5 5.1 Ritonavir PREZISTA ritonavir PREZISTA ritonavir darunavir ritonavir 5.2 PREZISTA /rtv N=3063 PREZISTA /rtv 0.5% 11
B C B C / HIV-1 PREZISTA /rtv PREZISTA /rtv 酶 AST/ALT PREZISTA /rtv PREZISTA /rtv / 5.3 n=3063 0.4% 12
/ 酶 Stevens-Johnson < 0.1% 疱 PREZISTA /rtv / PREZISTA /rtv 10.3% 6 PREZISTA /rtv 0.5% PREZISTA /rtv raltegravir PREZISTA /rtv + raltegravir 13
5.4 Darunavir sulfonamide sulfonamide PREZISTA PREZISTA /rtv sulfonamide 5.5 PREZISTA /rtv CYP3A CYP3A CYP3A PREZISTA /rtv CYP3A CYP3A PREZISTA /rtv PREZISTA /rtv PREZISTA /rtv 6 14
7 PREZISTA /rtv PREZISTA /rtv 4 7 5.6 / 酶 PI HIV PI PI 5.7 / 15
5.8 PREZISTA Mycobacterium avium cytomegalovirus Pneumocystis jirovecii PCP Graves' Guillainbarrè 5.9 酶 PIs A B 16
PIs PIs PI 5.10 3 23 26 darunavir 20 mg/kg 1000 mg/kg PREZISTA /ritonavir 3 8.1 8.4 12.3 6 5.2 5.3 / 5.6 5.7 17
5.8 5.9 PREZISTA ritonavir ritonavir ritonavir 6.1 TMC114-C211 3 TMC114-C211 689 HIV-1 PREZISTA /rtv 800/100 lopinavir/rtv 800/200 PREZISTA /rtv 800/100 lopinavir/rtv 800/200 18
162.5 153.5 PREZISTA /rtv 800/100 PREZISTA /rtv 800/100 5% 2 PREZISTA /rtv 2.3% H I V- 1 PREZISTA /rtv 800/100 2 2 19
2 2% HIV-1 PREZISTA /rtv 800/100 mg 2 * TMC114-C211 % PREZISTA /rtv 800/100 + TDF/FTC N=343 lopinavir/ritonavir 800/200 + TDF/FTC N=346 6% 6% 9% 16% 4% 4% 2% 4% 20
< 1% 3% 2% < 1% 7% 6% 6% 7% N= FTC=emtricitabine TDF=tenofovir disoproxil fumarate * 2% PREZISTA /rtv 21
800/100 mg 2 Stevens-Johnson PREZISTA /rtv 800/100 HIV-1 2-4 3 22
3 HIV-1 2-4 * TMC114-C211 PREZISTA /rtv lopinavir/rtv 800/100 800/200 % + TDF/FTC + TDF/FTC N=343 N=346 酶 ALT 2 > 2.5 5.0 ULN 9% 9% 3 > 5.0 10.0 ULN 3% 3% 4 > 10.0 ULN < 1% 3% 酶 AST 2 > 2.5 5.0 ULN 7% 10% 23
3 > 5.0 10.0 ULN 4% 2% 4 > 10.0 ULN 1% 3% 酶 2 > 2.5 5.0 ULN 1% 1% 3 > 5.0 10.0 ULN 0% < 1% 4 > 10.0 ULN 0% 0% 2 > 1.5 2.5 ULN < 1% 5% 3 > 2.5 5.0 ULN < 1% < 1% 4 > 5.0 ULN 0% 0% 24
2 5.65-8.48 mmol/l 500-750 mg/dl 3 8.49-13.56 mmol/l 751-1200 mg/dl 4 > 13.56 mmol/l > 1200 mg/dl 2 6.20-7.77 mmol/l 240-300 mg/dl 3 > 7.77 mmol/l > 300 mg/dl 3% 10% 2% 5% 1% 1% 23% 27% 1% 5% 25
2 3 2 3 4 酶 26 4.13-4.90 mmol/l 160-190 mg/dl 4.91 mmol/l 191 mg/dl 6.95-13.88 mmol/l 126-250 mg/dl 13.89-27.75 mmol/l 251-500 mg/dl > 27.75 mmol/l > 500 mg/dl 14% 12% 9% 6% 11% 10% 1% < 1% 0% 0%
2 > 1.5 3.0 ULN 3% 2% 3 > 3.0 5.0 ULN < 1% 1% 4 > 5.0 ULN 0% < 1% 酶 2 > 1.5 2.0 ULN 5% 2% 3 > 2.0 5.0 ULN 5% 4% 4 > 5.0 ULN 0% < 1% N= FTC=emtricitabine TDF=tenofovir disoproxil fumarate * 4 27
treatment-experienced TMC114-C214 3 TMC114-C214 595 HIV-1 PREZISTA /rtv 600/100 lopinavir/rtv 400/100 PREZISTA /rtv 600/100 lopinavir/rtv 400/100 80.7 76.4 PREZISTA /rtv 600/100 PREZISTA /rtv 600/100 5% 2 PREZISTA /rtv 4.7% HIV-1 PREZISTA / rtv 600/100 2 4 28
4 2% HIV-1 PREZISTA /rtv 600/100 mg 2 * TMC114-C214 % PREZISTA /rtv 600/100 + OBR N=298 lopinavir/rtv 400/100 + OBR N=297 2% < 1% 6% 3% 14% 20% 2% 1% 7% 6% 29
5% 3% 3% 1% 2% 1% 2% 2% 2% < 1% 3% 3% 7% 3% 30
N= OBR= * 2% PREZISTA /rtv 600/100 mg 2 PREZISTA /rtv 600/100 HIV-1 31
2-4 5 5 HIV-1 2-4 * TMC114-C214 % 32 PREZISTA /rtv 600/100 + OBR N=298 lopinavir/rtv 400/100 + OBR N=297 酶 ALT 2 > 2.5 5.0 ULN 7% 5% 3 > 5.0 10.0 ULN 2% 2%
4 > 10.0 ULN 1% 2% 酶 AST 2 > 2.5 5.0 ULN 6% 6% 3 > 5.0 10.0 ULN 2% 2% 4 > 10.0 ULN < 1% 2% 酶 2 > 2.5 5.0 ULN < 1% 0% 3 > 5.0 10.0 ULN < 1% < 1% 4 > 10.0 ULN 0% 0% 2 > 1.5 2.5 ULN < 1% 2% 33
3 > 2.5 5.0 ULN < 1% < 1% 4 > 5.0 ULN < 1% 0% 2 5.65-8.48 mmol/l 500-750 mg/dl 10% 11% 3 8.49-13.56 mmol/l 751-1200 mg/dl 7% 10% 4 > 13.56 mmol/l > 1200 mg/dl 3% 6% 2 6.20-7.77 mmol/l 240-300 mg/dl 25% 23% 34
3 > 7.77 mmol/l > 300 mg/dl 2 4.13-4.90 mmol/l 160-190 mg/dl 3 4.91 mmol/l 191 mg/dl 2 6.95-13.88 mmol/l 126-250 mg/dl 3 13.89-27.75 mmol/l 251-500 mg/dl 10% 14% 14% 14% 8% 9% 10% 11% 1% < 1% 35
4 > 27.75 mmol/l > 500 mg/dl < 1% 0% 酶 2 > 1.5 3.0 ULN 3% 4% 3 > 3.0 5.0 ULN 2% < 1% 4 > 5.0 ULN < 1% 0% 酶 2 > 1.5 2.0 ULN 6% 7% 3 > 2.0 5.0 ULN 7% 3% 4 > 5.0 ULN 0% 0% N= 36
OBR= * 4 2b 3 PREZISTA /rtv 2 Stevens-Johnson B / C B C PREZISTA /rtv PREZISTA /rtv 5.2 37
2 2 PREZISTA /ritonavir TMC114-C212 80 6 < 18 20 HIV-1 TMC114-C230 12 12 < 18 40 HIV-1 TMC114-C212 PREZISTA /ritonavir TMC114- C230 PREZISTA /ritonavir 8.4 14.4 TMC114-C212 PREZISTA /ritonavir 3% 13% 11% 10% 9% 5% 4% 3% 3 4 ALT 3 3% 4 1% AST 38
3 1% 酶 3 4% 4 1% 酶 3 1% 3 1% 3 3% TMC114-C230 PREZISTA /ritonavir 3% 33% 25% 16.7% 8.3% 8.3% 8.3% 8.3% 3 4 6.2 PREZISTA HMG-CoA 酶 PREZISTA /rtv 39
疱 5.3 7 7.1 PREZISTA /rtv PREZISTA ritonavir CYP3A CYP2D6 P-gp PREZISTA ritonavir CYP3A CYP2D6 P-gp 6 7.2 darunavir Darunavir ritonavir CYP3A darunavir P-gp CYP3A darunavir ritonavir darunavir ritonavir darunavir 40
ritonavir CYP3A P-gp darunavir ritonavir darunavir ritonavir 6 7.3 6 PREZISTA /rtv 4 12.3 6 4 12.3 11 12 Darunavir HIV-1 苷 酶 NRTIs 41
didanosine indinavir Indinavir indinavir/rtv 800/100 lopinavir/ ritonavir 42 darunavir didanosine HIV-1 HIV- 酶 PIs darunavir indinavir darunavir lopinavir Didanosine PREZISTA /rtv 1 2 Indinavir PREZISTA /rtv lopinavir/ritonavir PREZISTA ritonavir
saquinavir HIV 酶 atazanavir 7.4 darunavir saquinavir saquinavir PREZISTA ritonavir PREZISTA /ritonavir HIV-1 CCR5 co-receptor maraviroc maraviroc PREZISTA /rtv maraviroc 150 mg 43
amiodarone bepridil disopyramide flecainide lidocaine (systemic) mexiletine propafenone quinidine 4 PREZISTA /ritonavir digoxin digoxin digoxin digoxin digoxin 44
clarithromycin Apixaban dabigatran etexilate rivaroxaban darunavir clarithromycin clarithromycin PREZISTA /rtv CLcr 30-60 ml /min clarithromycin 50% CLcr < 30 ml /min clarithromycin 75% apixaban PREZISTA /rtv PREZISTA /rtv dabigatran etexilate dabigatran PREZISTA /rtv rivaroxaban 45
Warfarin carbamazepine phenobarbital phenytoin warfarin darunavir darunavir carbamazepine darunavir phenytoin phenobarbital PREZISTA /rtv warfarin warfarin PREZISTA /rtv INR PREZISTA /rtv carbamazepine PREZISTA /rtv carbamazepine carbamazepine PREZISTA /rtv phenytoin phenobarbital 46
paroxetine sertraline SSRI paroxetine sertraline TCA amitriptyline despiramine imipramine nortriptyline trazodone amtriptyline desipramine imipramine nortriptyline trazodone sertraline paroxetine PREZISTA /rtv SSRI sertraline paroxetine PREZISTA /rtv trazodone 47
darunavir itraconazole itraconazole ketoconazole posaconalzole ketoconazole posaconazole voriconazole voriconazole PREZISTA /rtv itaconazole ketoconazole posaconazole ketoconazole itraconazole 200 darunavir/rtv voriconazole / voriconazole 48
colchicine colchicine colcicine PREZISTA /ritonavir 4 PREZISTA /rtv colchicine 0.6 mg 1 x1 1 0.3 mg 3 PREZISTA /rtv colchicine 0.6 mg 0.3 mg 0.6 mg 0.3 mg 49
artemether/ lumefantrine rifabutin Rifabutin 300 50 PREZISTA / rtv colchicine 0.6 mg 0.3 mg artemether PREZISTA /rtv artemether/lumefantrine dihydroartemisinin lumefantrine lumefantrine QT darunavir darunavir rifabutin 25-Odesacetylrifabutin 4 rifabutin 300 75% 150 rifabutin
rifapentine darunavir PREZISTA /rtv rifapentine dasatinib nilotinib dasatinib nilotinib dasatinib nilotinib vinblastine vincristine vincristine vinblastine PREZISTA / rtv vincristine vinblastine ritonavir CYP3A P-gp 51
quetiapine quetiapine 4 PREZISTA /rtv quetiapine quetiapine quetiapine quetiapine quetiapine quetiapine PREZISTA /rtv quetiapine quetiapine 52
risperdone thioridazine β carvedilol metoprolol timolol amlodipine diltiazem felodipine nicardipine nifedipine verapamil β PREZISTA /rtv PREZISTA /rtv beta 53
/ darunavir / / betamethasone budesonide ciclesonide dexamethasone fluticasone methylprednisolone mometasone prednisone triamcinolone PREZISTA /rtv dexamethasone CYP3A darunavir CYP3A beclomethasone prednisolone / CYP3A 54
bosentan bosentan PREZISTA /rtv bosentan PREZISTA /rtv 10 62.5 mg bosentan bosentan PREZISTA /rtv PREZISTA /rtv bosentan 36 PREZISTA /rtv 10 62.5 mg bosentan 55
C HCV simeprevir NS3-4A 酶 boceprevir simeprevir darunavir darunavir boceprevir C 4 PREZISTA /rtv simeprevir PREZISTA /rtv boceprevir 56
HMG-CoA 酶 atorvastatin HMG-CoA 酶 pravastatin rosuvastatin cyclosporine tacrolimus sirolimus HMG-CoA 酶 4 PREZISTA /rtv HMG-CoA 酶 atorvastatin pravastatin rosuvastatin Atorvastatin 20 mg /day PREZISTA /rtv cyclosporine tacrolimus sirolimus PREZISTA /rtv 57
/ everolimus beta salmeterol / buprenorphine buprenorphine/ naloxone 58 salmeterol buprenorphine naloxone norbuprenorphine metabolite everolimus PREZISTA /rtv salmeterol PREZISTA /rtv salmeterol QT PREZISTA /rtv buprenorphine buprenorphine/naloxone PREZISTA /rtv buprenorphine buprenorphine/naloxone
methadone methadone PREZISTA /ritonavir methadone methadone / ethinyl estradiol norethindrone ethinyl estradiol norethindrone 8.3 59
PDE-5 avanafil sildenafil tadalafil vardenafil PDE-5 sildenafil PREZISTA /rtv PREZISTA /rtv PDE-5 PDE-5 PAH sildenafil PREZISTA /rtv 4 Tadalafil PREZISTA /rtv PREZISTA /rtv tadalafil PREZISTA /rtv 20 mg tadalafil 40 mg tadalafil PREZISTA /rtv 60
PREZISTA /rtv tadalafil PREZISTA /rtv tadalafil 24 PREZISTA /rtv 20 mg tadalafil 40 mg PDE-5 48 sildenafil 25 72 vardenafil 2.5 72 tadalafil 10 PDE-5 PREZISTA /rtv avanafil 61
omeprazole / CYP3A buspirone diazepam estazolam zoldipem omeprazole darunavir / omeprazole PREZISTA /ritonavir omeprazole omeprazole 40 omeprazole / 4 CYP3A / PREZISTA /rtv / 62
midazolam midazolam / midazolam midazolam 7.4 PREZISTA PREZISTA /ritonavir atazanavir dolutegravir efavirenz etravirine nevirapine 苷 酶 abacavir emtricitabine lamivudine stavudine tenofovir disoproxil fumarate zidovudine pitavastatin raltegravir ranitidine rilpivirine 63
8 8.1 APR darunavir 2.7% MACDP 2.7% APR MACDP MACDP 20 APR 15-20% AUC 3 1 64
PREZISTA 600 ritonavir 100 PREZISTA 600 PREZISTA 800 ritonavir 100 PREZISTA 800 ritonavir 100 HIV-1 RNA 50 copies/ml PREZISTA 600 ritonavir 100 2.4 12.3 34 PREZISTA / ritonavir 600/100 800/100 darunavir ritonavir 65
6-12 29 PREZISTA /ritonavir PREZISTA /ritonavir HIV-1 12.3 APR darunavir 615 385 230 / darunavir MACDP darunavir 2.6% 95% CI 1.2% 4.7% / darunavir 1.7% 95% CI 0.5% 4.4% 66
darunavir 6-15 1000 / darunavir 7-19 1000 / ritonavir 8-20 1000 / / darunavir darunavir AUC darunavir ritonavir 3 1 8.2 HIV HIV darunavir Darunavir 67
1 HIV HIV 2 HIV 3 PREZISTA 8.4 darunavir ritonavir darunavir Darunavir 1000 / ritonavir ritonavir 50% 8.3 PREZISTA 68
7.3 8.4 20 mg/kg 1000 mg/kg 23-26 PREZISTA /ritonavir 3 5.10 8.1 12.3 TMC114-C212 80 6 18 HIV-1 PREZISTA /ritonavir 6.1 12.3 14.4 6.1 40 2.5 TMC114-C230 12 18 HIV-1 69
12 PREZISTA /ritonavir 6.1 12.3 14.4 6.1 3 12 12 PREZISTA /ritonavir PREZISTA 12.3 40 2.5 darunavir 1000 / 0.1 1.0 5 4 23 2 3 2 ritonavir 70
8.5 PREZISTA 65 PREZISTA 12.3 8.6 PREZISTA /rtv PREZISTA /rtv PREZISTA /rtv 2.3 12.3 8.7 CrCL 30-60 / 71
n=20 HIV darunavir HIV-1 darunavir darunavir ritonavir 12.3 10 PREZISTA /rtv PREZISTA PREZISTA PREZISTA 72
11 PREZISTA darunavir HIV 酶 PREZISTA darunavir darunavir ethanolate [ 1S,2R -3-[[ 4-aminophenyl sulfonyl] 2-methylpropyl amino]-2-hydroxy-1- phenylmethyl propyl]-carbamic acid 3R,3aS,6aR -hexahydrofuro[2,3-b]furan-3- yl ester monoethanolate C27H37N3O7S C2H5OH 593.73 Darunavir ethanolate H O O O H O O H O N N S H H H OH H 3 NH 2 2H 5OH 3 73
Darunavir ethanolate 20 0.15 / PREZISTA 400 400 400 darunavir darunavir ethanolate PREZISTA 800 800 800 darunavir darunavir ethanolate ethanolate colloidal silicon dioxide crospovidone magnesium stearate microcristalline cellulose 800 hypromellose 400 OPADRY Orange FD&C Yellow No.6 polyethylene glycol 3350 polyvinyl alcohol-partially hydrolyzed talc titanium dioxide 800 OPADRY Dark Red iron oxide red polyethylene glycol 3350 polyvinyl alcohol-partially hydrolyzed talc titanium dioxide 74
PREZISTA darunavir 12 12.1 Darunavir HIV-1 12.4 12.2 40 QT/QTc 1.33 PREZISTA /ritonavir QT/QTc 12.3 Darunavir CYP3A Ritonavir CYP3A 75
darunavir 600 PREZISTA 100 ritonavir darunavir 14 PREZISTA 100 ritonavir darunavir HIV-1 darunavir ritonavir 100 7 darunavir PREZISTA /rtv 600/100 TMC114-C214 285 TMC114- C229 278 TMC114-C202 TMC114-C213 119 PREZISTA /rtv 800/100 TMC114-C211 335 TMC114-C229 280 HIV-1 76
7 Darunavir PREZISTA /rtv 800/100 TMC114-C211 TMC114-C229 48 PREZISTA /rtv 600/100 TMC114-C214 TMC114-C229 48 TMC114-C213 TMC114-C202 24 AUC24h ng h/ml * PREZISTA /ritonavir 800/100 TMC114-C211 TMC114-C229 TMC114-C214 N=335 N=280 N=285 PREZISTA /ritonavir 600/100 TMC114-C229 TMC114-C213 N=278 +TMC114- C202 N=119 77
78 93026 27050 87854 45000-219240 93334 28626 87788 45456-236920 116796 33594 111632 64874-355360 114302 32681 109401 48934-323820 124698 32286 123336 67714-212980 C0h ng/ml 2282 1168 2160 1201 3490 1401 3386 1372 3578 1151 2041 1896 3307 3197 3539 368-7242 184-7881 1517-13198 250-11865 1255-7368 N= *AUC24h AUC12h*2
100 ritonavir darunavir Tmax 2.5-4 600 darunavir 100 ritonavir 37% 82% PREZISTA /ritonavir P P-gp ritonavir darunavir C max AUC 40% darunavir 240 12 928 56 Darunavir 95% Darunavir alpha-1-acid glycoprotein AAG 79
HLMs darunavir Darunavir CYP CYP3A 400 14 C-darunavir 100 ritonavir darunavir Darunavir HIV-1 darunavir 90% 400 14 C-darunavir 100 ritonavir 79.5% 13.9% 14 C-darunavir darunavir 41.2% 7.7% ritonavir darunavir 15 100 ritonavir darunavir 32.8 / 5.9 / 80
Darunavir n=16 Child- Pugh Class A n=8 Child-Pugh Class B n=8 600/100 PREZISTA /rtv darunavir darunavir 2.6 8.6 B C HIV-1 TMC114-C211 TMC114-C214 48 B / C darunavir 14 C-PREZISTA /ritonavir 7.7% 81
darunavir darunavir ritonavir darunavir CrCL 30-60 / n=20 HIV-1 HIV-1 8.7 HIV-1 darunavir HIV-1 darunavir darunavir 82
HIV-1 18 75 HIV-1 n=12 65 darunavir 8.5 PREZISTA /ritonavir 74 HIV-1 6 18 20 darunavir ritonavir PREZISTA / ritonavir 600/100 darunavir darunavir 2.5 PREZISTA /ritonavir 12 HIV-1 12 18 40 darunavir ritonavir PREZISTA /ritonavir 800/100 darunavir 83
PREZISTA /ritonavir 800/100 darunavir 2.5 PREZISTA /ritonavir 800/100 darunavir 6 12 PREZISTA /ritonavir darunavir 2.5 PREZISTA /ritonavir 8 darunavir TMC114-C230 TMC114- C212 2.5 PREZISTA /ritonavir PREZISTA /ritonavir 84
AUC 24h ng h/ml C0h ng/ml TMC114-C230 N=12 84390 23587 86741 35527 123325 2141 865 2234 542 3776 TMC114-C212 N=74 126377 34356 127340 67054 230720 3948 1363 3888 1836 7821 85
N= AUC24h AUC12h*2 12 < 18 HIV-1 800/100 DRV/ rtv DRV 48 PREZISTA /ritonavir 600/100 PREZISTA / ritonavir 800/100 darunavir ritonavir 9 10 1 9 2 3 PREZISTA /ritonavir 600/100 Darunavir darunavir 86 2 n=11 * 3 n=11 6-12 n=11
Cmax ng/ml 4601 1125 5111 1517 6499 2411 AUC24h ng h/ml 77900 20020 87400 32800 110600 54040 Cmin ng/ml 1980 839.9 2498 1193 2711 2268 * AUC24h n=10 LLOQ Cmin n=10 AUC24h AUC12h*2 10 2 3 PREZISTA /ritonavir 800/100 Darunavir darunavir 2 n=16 3 n=14 6-12 n=15 Cmax ng/ml 4988 1551 5138 1243 7445 1674 87
AUC24h ng h/ml 61303 16232 60439 14052 94529 28572 Cmin ng/ml* 1193 509 1098 609 1572 1108 * N=12 2 N=15 3 N=14 darunavir darunavir 1 88
1 2 3 P R E Z I S TA / ritonavir 600/100 800/100 Darunavir AUC, 整體 Cmin, 整體 第 2 孕期第 3 孕期 AUC, 未結合 Cmin, 未結合 PREZISTA /ritonavi 每日兩次 幾何平均比 幾何平均比 (90%CI) 0.0 0.5 1.0 1.5 2.0 2.5 0.76(0.63,0.90) 0.83(0.72,0.97) 0.83(0.46,1.49) 1.02(0.59,1.78) 0.92(0.66,1.3) 0.93(0.69,1.24) 1.1(0.59,2.06) 1.14(0.59,2.2) 89
AUC, 整體 Cmin, 整體 第 2 孕期第 3 孕期 AUC, 未結合 PREZISTA /ritonavir 每日一次 幾何平均比 (90%CI) 0.66(0.6,0.74) 0.65(0.57,0.74) 0.68(0.56,0.83) 0.5(0.35,0.73) 0.76(0.67,0.85) 0.8(0.71,0.89) 90 0.87(0.69,1.1) Cmin, 未結合 0.62(0.43,0.9) 0.0 0.5 1.0 1.5 2.0 2.5 幾何平均比
90% CI 90% GMR 1.0 0.8 1.25 4 5.5 7 Darunavir ritonavir CYP3A CYP2D6 P-gp PREZISTA ritonavir CYP3A CYP2D6 P-gp Darunavir ritonavir CYP3A darunavir P-gp CYP3A darunavir ritonavir darunavir ritonavir darunavir ritonavir CYP3A P-gp darunavir ritonavir darunavir ritonavir darunavir 91
darunavir AUC Cmax Cmin 11 darunavir 12 darunavir 7 darunavir darunavir 11 Darunavir HIV 酶 92 / / darunavir 90% CI =1.00 Darunavir/ ritonavir N PK Cmax AUC Cmin
Saquinavir hard gel capsule 533/133.3 mg b.i.d. 1000 mg b.i.d. 400/100 mg b.i.d. HIV Didanosine 400 mg q.d. 600/100 mg b.i.d. 1200 mg 15 0.79 0.64- b.i.d. 0.97 14 0.83 0.75-0.92 17 0.93 0.86-1.00 1.01 0.95-1.07 Atazanavir 300 mg q.d.* 400/100 mg b.i.d. 13 1.02 0.96-1.09 Indinavir 800 mg b.i.d. 400/100 mg 9 1.11 0.98- b.i.d. 1.26 Lopinavir/ 400/100 mg 1200/100 mg 14 0.79 0.67- ritonavir b.i.d. b.i.d. 0.92 1.03 0.94-1.12 1.24 1.09-1.42 0.62 0.53-0.73 0.59 0.50-0.70 0.74 0.63-0.86 1.01 0.88-1.16 1.44 1.13-1.82 0.49 0.39-0.63 0.45 0.38-0.52 0.58 0.47-0.72 1.07 0.95-1.21 93
Efavirenz 600 mg q.d. 300/100 mg b.i.d. Etravirine 200 mg b.i.d. 600/100 mg b.i.d. Nevirapine 200 mg b.i.d. 400/100 mg b.i.d. Tenofovir disoproxil fumarate 300 mg q.d. 300/100 mg b.i.d. HCV NS3-4A 酶 Boceprevir 800 mg t.i.d. 600/100 mg b.i.d. 12 0.85 0.72-1.00 15 1.11 1.01-1.22 8 1.40 1.14-1.73 12 1.16 0.94-1.42 11 0.64 0.58-0.71 0.87 0.75-1.01 1.15 1.05-1.26 1.24 0.97-1.57 1.21 0.95-1.54 0.56 0.51-0.61 0.69 0.54-0.87 1.02 0.90-1.17 1.02 0.79-1.32 1.24 0.90-1.69 0.41 0.38-0.45 94
Simeprevir 50 mg q.d. 800 mg q.d. 25 + 1.04 0.99-1.10 Artemether/ lumefatrine 80/480 mg 6 doses at 0, 8, 24, 36, 48, and 60 hours 600/100 mg b.i.d. 14 1.00 0.93-1.07 1.18 1.11-1.25 0.96 0.90-1.03 Carbamazepine 200 mg b.i.d. 600/100 mg b.i.d. 16 1.04 0.93-1.16 Clarithromycin 500 mg b.i.d. 400/100 mg 17 0.83 0.72- b.i.d. 0.96 Ketoconazole 200 mg b.i.d. 400/100 mg 14 1.21 1.04- b.i.d. 1.40 0.99 0.90-1.08 0.87 0.75-1.01 1.42 1.23-1.65 1.31 1.13-1.52 0.87 0.77-0.98 0.85 0.73-1.00 1.01 0.81-1.26 1.73 1.39-2.14 95
Omeprazole 20 mg q.d. 400/100 mg b.i.d. Paroxetine 20 mg q.d. 400/100 mg b.i.d. Pitavastatin 4 mg q.d. 800/100 mg q.d. Ranitidine 150 mg b.i.d. 400/100 mg b.i.d. Rifabutin 150 mg q.o.d. 600/100 mg b.i.d. Sertraline 50 mg q.d. 400/100 mg b.i.d. 16 1.02 0.95-1.09 16 0.97 0.92-1.02 27 1.06 1.00-1.12 16 0.96 0.89-1.05 11 1.42 1.21-1.67 13 1.01 0.89-1.14 1.04 0.96-1.13 1.02 0.95-1.10 1.03 0.95-1.12 0.95 0.90-1.01 1.57 1.28-1.93 0.98 0.84-1.14 1.08 0.93-1.25 1.07 0.96-1.19 NA 0.94 0.90-0.99 1.75 1.28-2.37 0.94 0.76-1.16 N= 96
* q.d.= b.i.d.= darunavir PREZISTA /ritonavir 600/100 q.o.d.= AUC AUC 0-last N=10 Cmin Simeprevir 50 PREZISTA / ritonavir simeprevir 150 mg + 97
12 PREZISTA /ritonavir HIV 酶 / / Darunavir 90% CI =1.00 Darunavir/ ritonavir N PK Cmax AUC Cmin 98
Atazanavir Indinavir 300 mg q.d.*/ 100 mg ritonavir q.d. 300 mg q.d. darunavir/ritonavir 400/100 mg b.i.d. 800 mg b.i.d./ 400/100 mg 100 mg ritonavir b.i.d. b.i.d. 800 mg b.i.d. darunavir/ ritonavir 13 0.89 0.78-1.01 9 1.08 0.95-1.22 1.08 0.94-1.24 1.23 1.06-1.42 1.52 0.99-2.34 2.25 1.63-3.10 99
Lopinavir/ ritonavir Saquinavir 400/100 mg b.i.d. 1200/100 mg 14 0.98 0.78-1.09 0.86-1.23 0.90- b.i.d. 1.22 1.37 1.69 533/133.3 mg b.i.d. 1000 mg b.i.d./ 100 mg ritonavir b.i.d. 1000 mg b.i.d. darunavir/ritonavir HIV 1200 mg b.i.d. 400/100 mg b.i.d. 15 1.11 0.96-1.30 12 0.94 0.78-1.13 1.09 0.96-1.24 0.94 0.76-1.17 1.13 0.90-1.42 0.82 0.52-1.30 100
Didanosine 400 mg q.d. 600/100 mg b.i.d. Dolutegravir 30 mg q.d. 600/100 mg b.i.d 17 0.84 0.59-1.20 15 0.89 0.83-0.97 0.91 0.75-1.10 0.78 0.72-0.85-0.62 Ω 0.56-0.69 Dolutegravir 50 mg q.d. 600/100 mg 9 0.88 0.78-0.75 0.69-0.63 0.52- Ω b.i.d. with 200 mg b.i.d. etravirine 1.00 0.81 0.76 Efavirenz 600 mg q.d. 300/100 mg b.i.d. Etravirine 100 mg b.i.d. 600/100 mg b.i.d. 12 1.15 0.97-1.35 14 0.68 0.57-0.82 1.21 1.08-1.36 0.63 0.54-0.73 1.17 1.01-1.36 0.51 0.44-0.61 101
Nevirapine 200 mg b.i.d. 400/100 mg b.i.d. Rilpivirine 150 mg q.d. 800/100 mg q.d. Tenofovir disoproxil fumarate 102 300 mg q.d. 300/100 mg b.i.d. Maraviroc 150 mg b.i.d. 600/100 mg b.i.d. 8 1.18 1.02-1.37 14 1.79 1.56-2.06 12 1.24 1.08-1.42 12 2.29 1.46-3.59 1.27 1.12-1.44 2.30 1.98-2.67 1.22 1.10-1.35 4.05 2.94-5.59 1.47 1.20-1.82 2.78 2.39-3.24 1.37 1.19-1.57 8.00 6.35-10.1 600/100 mg 10 1.77 1.20-3.10 2.57-5.27 4.51- b.i.d. with 200 mg b.i.d. etravirine 2.60 3.74 6.15
HCV NS3-4A 酶 Boceprevir 800 mg t.i.d. 600/100 mg 12 b.i.d. Simeprevir 50 mg q.d. 800/100 mg 25 + q.d. Atorvastatin 0.75 0.67-0.68 0.65-0.65 0.56-0.85 0.72 0.76 1.79 1.55-2.59 2.15-4.58 3.54-2.06 3.11 5.92 40 mg q.d. 300/100 mg 15 0.56 0.48-0.85 0.76-1.81 1.37-10 mg q.d. darunavir/ ritonavir b.i.d. 0.67 0.97 2.40 103
Artemether Dihydroartemisinin 104 80 mg 600/100 mg b.i.d. Artemether artemether/ Dihydroartemisinin Lumefantrine Lumefantrine 80/480 mg 6 doses at 0, 8, 24, 36, 48, and 60 hours Buprenorphine/ Naloxone 8/2 mg 16/4 mg q.d. 600/100 mg b.i.d. 600/100 mg b.i.d. 15 0.85 0.68-1.05 15 1.06 0.82-1.39 15 0.82 0.61-1.11 15 0.82 0.66-1.01 15 1.65 1.49-1.83 17 0.92 0.79-1.08 0.91 0.78-1.06 1.12 0.96-1.30 0.84 0.69-1.02 0.82 0.74-0.91 2.75 2.46-3.08 - - 0.97 0.90-1.05 1.00 0.82-1.22 2.26 1.92-2.67 0.89 0.78-0.98 0.82-1.02 1.16
Norbuprenorphine 17 1.36 1.06-1.74 Carbamazepine 200 mg b.i.d. 600/100 mg b.i.d. Carbamazepine epoxide Clarithromycin 500 mg b.i.d. 400/100 mg b.i.d. Dextromethorphan 30 mg 600/100 mg b.i.d. 16 1.43 1.34-1.53 16 0.46 0.43-0.49 17 1.26 1.03-1.54 12 2.27 1.59-3.26 Dextrorphan 0.87 0.77-0.98 1.46 1.15-1.85 1.45 1.35-1.57 0.46 0.44-0.49 1.57 1.35-1.84 2.70 1.80-4.05 0.96 0.90-1.03 1.71 1.29-2.27 1.54 1.41-1.68 0.48 0.45-0.51 2.74 2.30-3.26 - - 105
Digoxin 0.4 mg 600/100 mg b.i.d. Ethinyl Estradiol EE 106 8 1.15 0.89-1.48 1.36 0.81-2.27 Ortho-Novum 1/35 600/100 mg 11 0.68 0.61-0.56 0.50-0.38 0.27-35 µg EE/1 mg NE b.i.d. 0.74 0.63 0.54 Norethindrone NE Ketoconazole 200 mg b.i.d. 400/100 mg b.i.d. R-Methadone 55-150 mg q.d. 600/100 mg b.i.d. Omeprazole 40 mg 600/100 mg b.i.d. 11 0.90 0.83-0.97 15 2.11 1.81-2.44 16 0.76 0.71-0.81 12 0.66 0.48-0.90 0.86 0.75-0.98 3.12 2.65-3.68 0.84 0.78-0.91 0.58 0.50-0.66-0.70 0.51-0.97 9.68 6.44-14.55 0.85 0.77-0.94 -
5-hydroxy omeprazole Paroxetine 20 mg q.d. 400/100 mg b.i.d. Pitavastatin 4 mg q.d. 800/100 mg q.d. Pravastatin 40 mg 600/100 mg b.i.d. Rifabutin 150 mg q.o.d. PREZISTA /rtv 0.93 0.71-1.21 16 0.64 0.59-0.71 27 0.96 0.84-1.09 14 1.63 0.95-2.82 0.84 0.77-0.92 0.61 0.56-0.66 0.74 0.69-0.80 1.81 1.23-2.66-0.63 0.55-0.73 NA 600/100 mg 11 0.72 0.55-0.93 0.80-1.64 1.48- b.i.d. # 0.93 1.09 1.81-107
25-O-desacetylrifabutin 300 mg q.d. Sertraline 50 mg q.d. 400/100 mg b.i.d. Sildenafil 11 4.77 4.04-5.63 13 0.56 0.49-0.63 7-OH-S-warfarin 12 1.42 1.24-1.63 108 9.81 8.09-11.9 0.51 0.46-0.58 100 mg 400/100 mg 16 0.62 0.55-0.97 0.86-25 mg darunavir/ ritonavir b.i.d. 0.70 1.09 S-warfarin 10 mg 600/100 mg b.i.d. 12 0.92 0.86-0.97 0.79 0.73-0.85 1.23 0.97-1.57 27.1 22.2-33.2 0.51 0.45-0.57 - - -
N= - = * q.d.= b.i.d.= lopinavir lopinavir/ritonavir 400/100 buprenorphine naloxone Cmax AUC24 PREZISTA /rtv buprenorphine/naloxone q.o.d.= rifabutin 300 N=11 dolutegravir C C24 + simeprevir PREZISTA /ritonavir 50 mg simeprevir 150 mg 109
12 PREZISTA /ritonavir CYP2D6 dextromethorphan CYP2C9 warfarin CYP2C19 omeprazole 12 12.4 Darunavir HIV-1 酶 HIV-1 Gag-Pol Darunavir T / HIV-1 HIV-2 EC50 1.2 8.5 nm 0.7 5.0 ng/ml darunavir HIV-1 M A B C D E F G O 110
EC50 < 0.1 4.3 nm Darunavir EC50 5.4 amprenavir atazanavir indinavir lopinavir nelfinavir ritonavir saquinavir tipranavir PIs abacavir didanosine emtricitabine lamivudine stavudine tenofovir zalcitabine zidovudine N t RTIs delavirdine rilpivirine efavirenz etravirine nevirapine NNRTIs enfuvirtide darunavir darunavir PREZISTA /ritonavir HIV-1 darunavir darunavir 21-88 酶 2 4 S37D R41E/T K55Q H69Q K70E T74S V77I I85V 9 PI HIV-1 darunavir HIV-1 111
22 酶 L10F V11I I13V I15V G16E L23I V32I L33F S37N M46I I47V I50V F53L L63P A71V G73S L76V V82I I84V T91A/S Q92R L10F V32I L33F S37N M46I I47V 150V L63P A71V I84V darunavir 8 酶 darunavir 50-641 EC50 125 nm 3461 nm treatment-experienced PREZISTA /ritonavir TMC114-C213 TMC114-C202 TMC114-C215 PREZISTA /rtv 600/100 TMC125-C206 TMC125-C216 etravirine < 50 copies/ml PREZISTA /rtv V32I I54L M 41% 25% PREZISTA /rtv V11I I15V L33F I47V I50V L89V 112
darunavir 90% darunavir > 7 darunavir 4.3 85 PREZISTA /rtv Gag 酶 TMC114-C212 PREZISTA /rtv V32I I54L L89M TMC114-C214 96 PREZISTA /rtv 600/100 mg 21% 62/298 lopinavir/rtv 400/100 mg 32% 96/297 PREZISTA /rtv 600/100 mg 7 7/43 16% PREZISTA /rtv PI darunavir 7 6 酶 darunavir > 7 PI V32I 113
L33F M46I L I47V I54L T74P L76V darunavir 59 839 lopinavir/rtv 31 31/75 41% lopinavir lopinavir > 10 L10I F M46I L I47V A I54V L76V 31 lopinavir/rtv 14 lopinavir > 10 TMC114-C229 48 4 PREZISTA /rtv 800/100 mg 26% 75/294 PREZISTA /rtv 600/100 mg 19% 56/296 PREZISTA /rtv 800/100 mg 8 8/60 13% IAS-USA 酶 PREZISTA /rtv 600/100 mg 5 5/39 13% darunavir PI PREZISTA /rtv 800/100 mg V32I M46I L76V I84V 114
darunavir 24 PREZISTA /rtv 600/100 mg L33F I50V darunavir 40 PREZISTA /rtv 800/100 mg PREZISTA /rtv 600/100 mg 7 7/60 12% 4 4/42 10% 苷 酶 NRTI PREZISTA /ritonavir TMC114- C211 4 192 PREZISTA /rtv 800/100 mg 22% 64/288 lopinavir/rtv 800/200 mg 29% 76/263 PREZISTA /rtv n=43 11 酶 darunavir darunavir > 7 lopinavir/rtv n=53 17 酶 lopinavir/rtv lopinavir 115
> 10 PREZISTA /rtv 4 7 lopinavir/rtv 酶 M184V / emtricitabine 酶 3309 amprenavir atazanavir indinavir lopinavir nelfinavir ritonavir saquinavir / tipranavir 90% darunavir < 10 PIs darunavir darunavir amprenavir atazanavir indinavir lopinavir nelfinavir ritonavir saquinavir 9 PI darunavir 6 tipranavir EC50 < 3 darunavir tipranavir TMC114-C213 TMC114-C202 TMC114-C215 116
tipranavir tipranavir > 3 PREZISTA / ritonavir 34% 64/187 96 HIV-1 RNA < 50 copies/ ml PREZISTA /rtv 600/100 > 7 41% tipranavir 10% saquinavir 2% 酶 amprenavir atazanavir indinavir lopinavir nelfinavir TMC114-C214 7 darunavir PREZISTA /rtv 酶 fos amprenavir atazanavir lopinavir indinavir nelfinavir 7 6 saquinavir 5 tipranavir 4 酶 Darunavir 苷 / 苷 酶 苷 酶 CCR5 酶 117
/ / PREZISTA / rtv 600/100 darunavir 2b TMC114-C213 TMC114-C202 TMC114-C215 n=439 96 etravirine TMC125-C206 TMC125-C216 n=591 24 5 IAS 酶 D30N V32I L33F M46I/L I47A/V G48V I50L/V I54L/M L76V V82A/F/L/ S/T I84V N88S L90M 13 13 PREZISTA /rtv 600/100 IAS PI TMC114-C213 TMC114-C202 TMC114- C215 118
#IAS PI 96 < 50 copies/ml N=439 ENF / ENF 44% 192/439 54% 61/112 40% 131/327 0-4 50% 162/322 58% 49/85 48% 113/237 5 22% 16/74 47% 9/19 13% 7/55 6 9% 3/32 17% 1/6 8% 2/26 ENF=enfuvirtide IAS PI 2008 D30N V32I L33F M46I/L I47A/V G48V I50L/ V I54L/M L76V V82A/F/L/S/T I84V N88S L90M V11I V32I L33F I47V I50V I54L M T74P L76V I84V L89V 2 PREZISTA /rtv 119
enfuvirtide 0-1 2 3 96 HIV-1 RNA < 50 copies/ml 59% 29% 12% darunavir darunavir 14 TMC114-C213 TMC114-C202 TMC114-C215 PREZISTA /rtv darunavir 14 PREZISTA /rtv 600/100 96 HIV-1 RNA < 50 copies/ml Darunavir Enfuvirtide TMC114-C213 TMC114-C202 TMC114-C215 DRV 120 96 < 50 copies/ml N=417
ENF / ENF 175/417 42% 61/112 54% 131/327 40% ENF=enfuvirtide 0-7 148/270 55% 44/65 68% 104/205 51% > 7-20 16/53 30% 7/17 41% 9/36 25% > 20 11/94 12% 6/23 26% 5/71 7% 13 13.1 104 darunavir 121
150 450 1000 / 50 150 500 / darunavir 600/100 800/100 darunavir AUC 0.4 0.7 0.7 1 darunavir Ames Darunavir 122
14 14.1 PREZISTA /rtv 2 HIV-1 TMC114- C211 TMC114-C214 3 192 2 HIV-1 2b TMC114-C213 TMC114-C202 96 14.2 TMC114-C211 TMC114-C211 3 HIV-1 PREZISTA /rtv 800/100 lopinavir/ritonavir 800/200 tenofovir disoproxil fumarate 300 123
TDF emtricitabine 200 FTC HIV-1 HIV-1 RNA 5000 copies/ml HIV-1 RNA < 100,000 copies/ml 100,000 copies/ml CD4+ < 200 cells/mm 3 200 cells/mm 3 HIV-1 RNA < 50 copies/ml TMC114-C211 192 689 PREZISTA /rtv lopinavir/ritonavir 15 15 TMC114-C211 PREZISTA /rtv 800/100 lopinavir/ritonavir 800/200 124
15 TMC114-C211 PREZISTA /rtv 800/100 lopinavir/ritonavir + TDF/FTC 800/200 + TDF/FTC N=343 N=346 34 18-70 33 19-68 70% 70% 30% 30% 40% 45% 125
23% 21% 23% 22% 13% 11% HIV-1 RNA log10 copies/ml CD4+ cells/mm 3 cells/mm 3 100,000 copies/ml 126 4.86 4.84 228 4-750 218 2-714 34% 35%
CD4+ < 200 cells/mm 3 41% 43% FTC=emtricitabine TDF=tenofovir disoproxil fumarate TMC114-C211 PREZISTA /rtv 800/100 192 16 16 TMC114-C211 192 PREZISTA /rtv 800/100 mg + TDF/FTC N=343 lopinavir/rtv 800/200 mg + TDF/FTC N=346 127
HIV-1 RNA < 50 copies/ml 70%* 61% 12% 15% 192 5% 13% 13% 12% < 1% 0% N= FTC=emtricitabine TDF=tenofovir disoproxil fumarate * 95% CI 1.9 16.1 192 192 50 copies 128
186-198 < 50 copies/ml TMC114-C211 192 CD4+ PREZISTA /rtv 800/100 mg 258 cells/mm 3 lopinavir/rtv 800/200 mg 263 cells/mm 3 PREZISTA /rtv 48 < 50 copies/ml 81% 192 lopinavir/rtv 68% 192 PREZISTA /rtv lopinavir/rtv ITT OP 14.3 treatment-experienced TMC114-C229 TMC114-C229 PREZISTA /rtv 800/100 mg PREZISTA / 129
rtv 600/100 mg HIV-1 darunavir V11I V32I L33F I47V I50V I54L I54M T74P L76V I84V L89V > 1,000 HIV-1 RNA copies/ml 2NRTIs HAART 12 HIV-1 HIV-1 RNA < 50 copies/ml 590 48 17 TMC114-C229 PREZISTA /rtv 800/100 mg PREZISTA /rtv 600/100 mg 130
17 TMC114-C229 PREZISTA /rtv 800/100 mg + OBR N=294 PREZISTA /rtv 600/100 mg + OBR N=296 40 18-70 40 18-77 61% 67% 39% 33% 35% 37% 131
28% 24% 16% 20% 16% 14% HIV-1 RNA log10 copies/ml 4.19 4.13 CD4+ cells/mm 3 cells/mm 3 100,000 copies/ml 219 24-1306 236 44-864 13% 11% 132
CD4+ < 200 cells/mm 3 Darunavir * 43% 39% 0.50 0.1-1.8 0.50 0.1-1.9 PI 3 4 NNRTI 2 1 NRTI 1 1 PIs 88% 86% 酶
0 84% 84% 1 8% 9% 2 5% 4% 3 3% 2% NRTIs 3 3 NNRTIs 1 1 PIs ritonavir 1 1 OBR= optimized background regimen * Antivirogram 134
Johnson VA, Brun-Vézinet F, Clotet B, et al. Update of the drug resistance mutations in HIV-1 December 2008. Top HIV Med 2008 16 5 138-145 ritonavir TMC114-C229 PREZISTA /rtv 800/100 mg 48 18 18 TMC114-C229 48 PREZISTA /rtv 800/100 mg + OBR N=294 PREZISTA /rtv 600/100 mg + OBR N=296 HIV-1 RNA < 50 copies/ml 69% 69% 135
* 26% 23% 48 3% 4% 2% 3% 0% < 1% N= OBR= optimized background regimen * 48 48 50 copies / HIV RNA 50 copies/ml 136
42-54 < 50 copies/ml CD4+ PREZISTA /rtv 800/100 mg 108 cells/mm 3 PREZISTA /rtv 600/100 mg 112 cells/mm 3 TMC114-C214 TMC114-C214 3 HIV-1 treatment-experienced lopinavir/ritonavir PREZISTA /rtv 600/100 lopinavir/ritonavir 400/100 NRTIs NNRTIs 137
HIV-1 HIV-1 RNA > 1000 copies/ml HAART 12 HIV-1 RNA < 400 copies/ml TMC114-C214 96 595 PREZISTA /rtv lopinavir/ritonavir 19 19 TMC114-C214 PREZISTA /rtv 600/100 lopinavir/ritonavir 400/100 19 TMC114-C214 138 PREZISTA /rtv 600/100 + OBR N=298 lopinavir/ritonavir 400/100 + OBR N=297
40 18-68 41 22-76 77% 81% 23% 19% 54% 57% 18% 17% 15% 15% 139
9% 9% HIV-1 RNA log10 copies/ml 4.33 4.28 CD4+ cells/mm 3 cells/mm 3 235 3-831 230 2-1096 100,000 copies/ml 19% 17% CD4+ < 200 cells/mm 3 40% 40% Darunavir 0.60 0.10-37.40 0.60 0.1-43.8 140
Lopinavir 0.70 0.40-74.40 0.80 0.30-74.50 * PI 4 4 NNRTI 1 1 NRTI 2 2 酶 * 1 78% 80% 2 8% 9% 3 13% 11% 141
ARVs NRTIs 4 4 NNRTIs 1 1 PIs ritonavir 1 1 PIs Darunavir 142 2% 3% OBR= optimized background regimen * Johnson VA, Brun-Vezinet F, Clotet B, et al. Update of the drug resistance mutations in HIV-1:Fall 2006. Top HIV Med 2006 14 3 125-130 ARVs ritonavir Antivirogram
PIs TMC114-C214 PREZISTA /rtv 600/100 96 20 20 TMC114-C214 96 PREZISTA /rtv 600/100 mg + OBR N=298 lopinavir/rtv 400/100 mg + OBR N=297 HIV-1 RNA < 50 copies/ml 58% 52% * 26% 33% 96 143
7% 8% 8% 7% 144 1% < 1% N= OBR= optimized background regimen * 96 96 50 copies 90-102 < 50 copies/ml
TMC114-C214 96 CD4+ PREZISTA /rtv 600/100 mg lopinavir/rtv 400/100 mg 81 cells/mm 3 93 cells/mm 3 TMC114-C213 TMC114-C202 TMC114-C213 TMC114-C202 PI 2b 2 PREZISTA /rtv 600/100 HIV-1 HIV-1 RNA > 1000 copies/ml PI s NNRTI s NRTI s PI D30N M46I/L G48V I50L/V V82A/F/S/T I84V L90M PI 8 PI enfuvirtide 145
PREZISTA /rtv OBR PI s OBR ARV PI s OBR OBR NRTIs enfuvirtide PI s lopinavir 36% fos amprenavir 34% saquinavir 35% atazanavir 17% 98% ritonavir PI 23% PIs 47% enfuvirtide 35% ENF HIV-1 RNA 1 log10 TMC114-C213 TMC114-C202 PREZISTA /rtv PI 21 21 TMC114-C213 TMC114-C202 PREZISTA /rtv 600/100 PI 146
21 TMC114-C213 TMC114-C202 PREZISTA /rtv 600/100 + OBR N=131 PI s + OBR N=124 43 44 27-73 25-65 89% 88% 11% 12% 147
81% 73% 10% 15% 7% 8% HIV-1 RNA log10 copies/ml CD4+ cells/mm 3 cells/mm 3 100,000 copies/ml 4.61 4.49 153 3-776 163 3-1274 24% 29% 148
CD4+ < 200 cells/mm 3 67% 58% Darunavir 4.3 3.3 * PI 12 12 NNRTI 1 1 NRTI 5 5 酶 * 1 8% 9% 2 22% 21% 149
3 70% 70% ARVs NRTIs 6 6 NNRTIs 1 1 PIs ritonavir 5 5 PIs Tipranavir Darunavir 150 63% 61% Enfuvirtide 20% 17% OBR= optimized background regimen * Johnson VA, Brun-Vezinet F, Clotet B, et al. Update of the drug resistance mutations in HIV-1 Fall 2006. Top HIV Med 2006 14 3 125-130
Antivirogram PIs TMC114-C213 TMC114-C202 PREZISTA / rtv 600/100 96 22 22 TMC114-C213 TMC114-C202 96 TMC114-C213 TMC114-C202 PREZISTA /rtv 600/100 + OBR N=131 PI + OBR N=124 151
96 HIV-1 RNA 1 log10 96 < 50 copies/ml 1 log10 152 57% 39% 10% 9% 29% 80% * 8% 53% 17% 19% 4% 8% 9% 3% 5% 7% OBR= optimized background regimen * 12 HIV-1 RNA 0.5 log10 1 log10 96
96 1 log10 TMC114-C213 TMC114-C202 48 PREZISTA /rtv600/100 PI HIV-1 RNA < 400 copies/ml 55.0% 14.5% PREZISTA /rtv 6 0 0 / 1 0 0 H I V- 1 R N A -1.69 log10 copies/ml PI -0.37 log10 copies/ml CD4+ PREZISTA /rtv 600/100 103 cells/mm 3 PI 17 cells/mm 3 14.4 PREZISTA /ritonavir 2 TMC114-C212 6 18 20 153
20 30 30 40 40 PREZISTA ritonavir 酶 80 PREZISTA /ritonavir ritonavir 44 ritonavir 23 100 mg ritonavir 80 14 6 18 71% 54% 30% 9% 8% HIV-1 RNA 4.64 log10 copies/ml CD4+ 330 cells/ mm 3 6 1505 cells/mm 3 38% HIV-1 RNA 100,000 copies/ml 79% 苷 酶 NNRTI 96% 酶 PI 154
96% 24 2 HIV-1 RNA 400 copies/ml 50 copies/ml 64% 50% CD4+ 117 cells/mm 3 TMC114-C230 12 18 40 PREZISTA /ritonavir 800/100 酶 12 14.4 12.6 17.3 33.3% 58.3% 41.7% HIV-1 RNA 4.72 log10 copies/ml CD4+ 282 cells/mm 3 204 515 cells/ mm 3 41.7% HIV-1 RNA 100,000 copies/ml 155
48 HIV-1 RNA 50 copies/ml 400 copies/ml 83.3% 91.7% CD4+ 221 10 6 cells/l 16 / PREZISTA darunavir 400 400 darunavir darunavir ethanolate 400 TMC PREZISTA darunavir 800 800 darunavir darunavir ethanolate 800 T PREZISTA 400 60 800 30 156
400 PROSOLV SMCC HD90 Crospovidone Colloidal Anhydrous Silica Magnesium Stearate OPADRY II light Orange 85F93377 800 Hypromellose 2910 15mPa.s Silicified Microcrystalline Cellulose Crospovidone Colloidal Silicon Dioxide Magnesium Stearate OPADRY II Dark Red 85F150004 PREZISTA 30 157
Janssen Ortho LLC State Road 933 KM 0.1 Mamey Ward, Gurabo, Puerto Rico, 00778, USA Janssen-Cilag S.P.A. Via C. Janssen, 04100 Borgo San Michele-Latina, Italy 319 8 0800-211-688 USPI Jun2017_v1801 Johnson & Johnson Taiwan Ltd. 2018 1801 158