ライフサイエンスコーパス: d4T

1 d4T with or without 3TC is a potential alternative to ZD

2 , ZDV/didanosine (ddI), stavudine (d4T)/3TC, d4T/ddI, and ddI/3TC.

3 D4T/3TC, d4T/ddI, and ddI/3TC have similar toxicity rates and are

4 anscriptase enzyme inhibitors AZT, ddI, 3TC, d4T, foscarnet, and nevirapine, as well as the protease

5 ially hydrolyzed phosphate diester, alaninyl d4T monophosphate.

6 ivatives of the anti-HIV nucleoside analogue d4T were prepared as potential membrane-soluble prodrugs

7 AU, and D-dideoxynucleoside analogs, ddC and d4T.

8 Moreover, the extensive use of ddI and d4T has led to high frequencies of the K65R mutation, fu

9 pport the clinical use of Zdv, ddC, ddI, and d4T but not of 3TC for the antiretroviral treatment of H

10 ther nucleoside analogs (i.e., ddC, ddI, and d4T).

11 re equally susceptible to Zdv, ddC, ddI, and d4T.

12 ro relative to the parent TMC-derivative and d4T, respectively.

13 s showed that increasing age, female sex and d4T exposure were associated with increased hazard of dr

14 s of these data suggests that zidovudine and d4T should not be prescribed in combination and that ddI

15 rmacologic antagonism between zidovudine and d4T.

16 Mean maternal antenatal d4T pharmacokinetics (terminal plasma half-life [T1/2],

17 inical toxicities than were those containing d4T (adjusted hazard ratio [HR], 0.49; P = .02) ); regim

18 have less toxicity than do those containing d4T, thereby supporting their use in first-line regimens

19 V prodrug 2',3'-didehydro-3'-deoxythymidine (d4T).

20 iple replication cycle were unable to detect d4T resistance in d4T-selected mutants with K65R but det

21 dideoxyadenosine (ddA), didehydrothymidine (d4T), or phosphonoformic acid (foscarnet) did not cause

22 I) > 2',3'-didehydro-2',3'-dideoxythymidine (d4T) >> (+)3TC >> (-)3TC > PMPA > azidothymidine (AZT) >

23 t/refusing pregnant women and of single-dose d4T in their infants.

24 ions (2.6 per 100 P/Ys) compared to 17.9 for d4T and 8.5 per 100 P/Ys for AZT.

25 ed with d4T, we identified a new pathway for d4T resistance mediated by K65R, a mutation not selected

26 ce and indicate that resistance pathways for d4T and AZT may not be identical.

27 The role of K65R in d4T resistance was confirmed in site-directed mutants ge

28 ycle were unable to detect d4T resistance in d4T-selected mutants with K65R but detected cross-resist

29 esults demonstrate that K65R plays a role in d4T resistance and indicate that resistance pathways for

30 tain antiviral activity following first-line d4T therapy.

31 failure of stavudine-lamivudine-nevirapine (d4T/3TC/NVP; P < .01), and K103N, V106M, and M184V with

32 The oral clearance of d4T in infants was significantly greater at week 6 versu

33 and K103N, V106M, and M184V with failure of d4T/3TC/efavirenz (EFV; P < .01).

34 which clearly demonstrate the generation of d4T mono-, di- and triphosphates from the prodrug, even

35 Examination of intracellular levels of d4T-triphosphate in 6 subjects was consistent with previ

36 ht the complexity of the genetic pathways of d4T resistance and its phenotypic expression.

37 ed for the majority of drug substitutions of d4T.

38 Notably, the higher toxicities of d4T, ddC, and ddA arose from their 13-36-fold tighter bi

39 uccessfully incorporates the triphosphate of d4T-4PEG-TMC bifunctional inhibitor in a base-specific m

40 This comprised 948 subjects on TDF, 3438 on d4T and 709 subjects on AZT.

41 their current regimen or to switch to ddI or d4T monotherapy.

42 nd 3TC for 6 weeks and a single dose of oral d4T at weeks 1 and 6.

43 ived oral 3TC and either intravenous or oral d4T.

44 eases in all arms except the zidovudine plus d4T arm.

45 Patients receiving zidovudine plus d4T showed progressive declines in CD4 cell counts with

46 in patients receiving d4T or zidovudine plus d4T.

47 Women received d4T and lamivudine (3TC) from enrollment until labor.

48 0.14 log(10) copies/mL in patients receiving d4T or zidovudine plus d4T.

49 Stavudine (d4T) and zidovudine (AZT) are thymidine analogs widely u

50 ine were randomized either to add stavudine (d4T) or didanosine (ddI) to their current regimen or to

51 (ddC), didanosine (ddI), 3TC, and stavudine (d4T) were determined, using an enzymatic assay, for 5 HT

52 The NRTIs zidovudine (AZT), stavudine (d4T), didanosine (ddI), and lamivudine (3TC), and the nu

53 dine (3TC), ZDV/didanosine (ddI), stavudine (d4T)/3TC, d4T/ddI, and ddI/3TC.

54 tutions and regimen switches from stavudine (d4T) and zidovudine (AZT) regimens have been well descri

55 nosine (ddI metabolized to ddA) > stavudine (d4T) >> lamivudine (3TC) > tenofovir (PMPA) > zidovudine

56 olerance, and pharmacokinetics of stavudine (d4T) in human immunodeficiency virus (HIV)-infected zido

57 on were similar for patients exposed to TDF, d4T and AZT, suggesting all regimens were equally effect

58 ddI provides greater antiviral activity than d4T in zidovudine-treated patients.

59 he most neurotoxic, followed by ddI and then d4T.

60 TC > CBV > AZT > PMPA approximately equal to d4T >> ddA (ddI) >> ddC.

61 Resistance to d4T is not fully understood, although the selection of A

62 with a high level of enzymatic resistance to d4T-triphosphate (median, 16-fold; range, 5- to 48-fold)

63 phenotypic characterization of resistance to d4T.

64 a novel bifunctional RT inhibitor utilizing d4T (NRTI) and a TMC-derivative (a diarylpyrimidine NNRT

65 a lower rate of clinical toxicities than was d4T/3TC.

66 lower rate of clinical toxicities than were d4T/ddI and ddI/3TC and with a higher rate of laboratory

67 es in nine recombinant viruses cultured with d4T, we identified a new pathway for d4T resistance medi

68 selection of T215Y in patients treated with d4T may be favored.

69 esistance mutations in patients treated with d4T suggests that both drugs have similar pathways of re