Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Research continues to show that early and aggressive treatment is effective for HIV treatment. However, when a patient needs to switch therapy, it is a sign that the treatment is not working well. Stopping therapy altogether is not a good option. Switching is sometimes valuable when a drug does not decrease viral loads to undetectable levels. Patients are cautioned that failure with one therapy does not necessarily indicate that other therapies will be intolerable or ineffective. Trials show that some combinations, such as AZT and Zerit, should not be used together. In planning treatment options, patients should always have a second viral load test to substantiate the results of the first. Tests for drug resistance are not yet approved by the Food and Drug Administration (FDA) and are not widely accepted. Many doctors believe that, due to resistance, any drug taken in the past will not be effective in the future. The new drug cocktails, several drugs used in combination with protease inhibitors, are increasingly becoming the treatment of choice. Contact information for trials involving amprenavir (141 W94) and PNU-140690 is provided.
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PMID:Making the switch--ideas for when therapy fails. 1136 88

Zerit (d4T) is as potent as Retrovir (AZT) in HIV combination therapy according to a University of Alabama study. This is important since either drug can often be a fundamental part of most HIV drug combinations. The study involved 204 participants in 48 weeks of therapy and used Zerit or Retrovir in combination with Crixivan or Epivir.
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PMID:Zerit vs. Retrovir. 1136 45

A brief review is provided for several oral presentations on HIV drugs delivered at the 6th Conference on Retroviruses and Opportunistic Infections. Topics cover cross resistance with respect to potential new drugs, the new protease inhibitor ABT-378, Triangle Pharmaceuticals' drug FTC, and one study on the different classes of anti-HIV drugs now on the market. Viral load reduction data are highlighted for Zerit/Videx when combined with 3TC, Viramune, or Indinavir. Contact information is provided.
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PMID:The latest antiviral news. 1136 51

Drug options, presented at the 6th Conference on Retroviruses and Opportunistic Infections, for HIV-infected people switching their regimen due to drug failure are examined. Alternatives discussed include use of Zerit after AZT, Epivir versus Rescriptor, and Sustiva versus Viracept. A study of Crixivan and the issue of resistance are also addressed. Results of some studies presented indicate that a switch to a new drug combination should include at least two new drugs, and that Sustiva and Viracept used together with two nukes were better than a Viracept triple combination. Final comments briefly explore the relationship between drug failure and CD4+ T-cell count.
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PMID:For people needing a new drug. 1136 52

The synthesis of phenyl-substituted and benzoannulated cycloSal phosphate triesters of the nucleoside analogue 2',3'-dideoxy-2',3'-didehydrothymidine (d4T, Zerit) as lipophilic, membrane-soluble pronucleotides is described. The cycloSal moiety was introduced by using cyclic chlorophosphite agents prepared from phenyl-substituted saligenin derivatives and ortho-hydroxymethylated naphthols, respectively. Hydrolysis studies (HPLC analysis) of the triesters 2, 3 showed a range of hydrolytic stability from 1.4 h up to 5.1 h and the stability could be correlated with the substitution pattern in the cycloSal moiety. A slight decrease of their stability was observed, if phenyl-substituted derivatives were hydrolyzed in human CEM/O cell extracts. D4T and thymine, possible products of enzymatic cleavage of the pronucleotides, were not detected in the cell extracts. A further investigation of the hydrolysis process was performed by 31P-NMR spectroscopy. This technique allowed a precise monitoring of the degradation products and the exact determination of the product ratio. Finally, the newly synthesized compounds were tested concerning their antiviral activity against HIV in vitro. A strong correlation of the hydrolysis properties and the antiviral activity was found. 3-phenyl-cycloSal-d4TMP showed a threefold increase in its anti-HIV-1 activity and retained full activity in thymidine kinase (TK) deficient cells, indicative of a successful TK-bypass.
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PMID:Aryl-substituted and benzo-annulated cyc/osal-derivatives of 2',3'-dideoxy-2',3'-didehydrothymidine monophosphate--correlation of structure, hydrolysis properties and anti-HIV activity. 1223 30

The in vivo toxicity and pharmacokinetics of stampidine (CAS 217178-62-6), an aryl phosphate derivative of stavudine (CAS 3056-17-5) under development as a new anti-human immunodeficiency virus (anti-HIV) agent, were studied in mice and rats. Stampide was very well tolerated by both mice and rats without any toxicity at cumulative dose levels > 1 g/kg. Therapeutic micromolar plasma concentrations of stampidine and its active metabolites ala-STV-MP (CAS 180076-92-0) and STV were rapidly achieved and maintained several hours after i.p. administration of the nontoxic 25-50 mg/kg bolus doses of stampidine. The remarkable in vivo safety of stampidine warrants the further development of this promising new antiviral agent for possible clinical use in HIV-infected patients.
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PMID:Toxicity and pharmacokinetics of stampidine in mice and rats. 1285 63

Stampidine [2',3'-didehydro-2',3'-dideoxythymidine 5'-[p-bromophenyl methoxyalaninyl phosphate], a prodrug of stavudine (STV/d4T) with improved anti-HIV activity, is undergoing development as a novel nonspermicidal microbicide. Here, we report the stability of stampidine as a function of pH, preparation of a novel thermoreversible ovule formulation for mucosal delivery, its dissolution profile in synthetic vaginal fluid, and its mucosal toxicity potential as well as systemic absorption in the rabbit model. Stampidine was most stable under acidic conditions. Stampidine was solubilized in a thermoreversible ovule formulation composed of polyethylene glycol 400, polyethylene glycol fatty acid esters, and polysorbate 80. Does were exposed intravaginally for 14 days to an ovule formulation with and without 0.5%, 1%, or 2% stampidine corresponding to 1 x 107- to 4 x 107-fold higher than its in vitro anti-HIV IC50 value. Vaginal tissues harvested on Day 15 were evaluated for mucosal toxicity and cellular inflammation. Additionally, does were exposed intravaginally to stampidine, and plasma collected at various time points was assayed by analytical HPLC for the prodrug and its bioactive metabolites. Stampidine did not cause mucosal inflammation. The vaginal irritation scores for 0.5-2% stampidine were within the acceptable range for clinical trials. The prodrug and its major metabolites were undetectable in the blood plasma. The marked stability of stampidine at acidic pH, its rapid spreadability, together with its lack of mucosal toxicity or systemic absorption of stampidine via a thermoreversible ovule may provide the foundation for its clinical development as an easy-to-use, safe, and effective broad-spectrum anti-HIV microbicide without contraceptive activity.
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PMID:Development and evaluation of a thermoreversible ovule formulation of stampidine, a novel nonspermicidal broad-spectrum anti-human immunodeficiency virus microbicide. 1289 Jul 26

Stavudine (d4T), a thymidine nucleoside analogue has been effectively used for treatment of patients infected with HIV. A randomized, two-way, crossover study was conducted in 24 fasting, healthy, Caucasian male volunteers to compare plasma pharmacokinetic (PK) profile and single-dose tolerability of a new d4T formulation (Stavir, Cipla Ltd, India; 40 mg capsule, test, T) with that of reference (R) formulation (Zerit), Bristol-Myers Squib, NJ, USA; capsule, 40 mg). Each volunteer received T and R formulation separated by at least 10 days of drug free wash-out period. Plasma concentrations of d4T, determined upto 24h post-dose by a validated LC-MS/MS assay were utilized to assess PK parameters such as maximum observed plasma concentration (Cmax), time to Cmax (tmax), and area under plasma concentration curve (AUC(infinity)). The primary plasma PK parameters, Cmax, and AUC(infinity), of anti-retroviral were comparable for either of the formulations. tmax was achieved within an hour suggesting rapid absorption of d4T from both formulations. Geometric mean ratios (GMR) (percentage reference) of AUC(infinity) and Cmax, and their 90% confidence intervals (CI) were 106.32 [102.52-110.26] and 102.32 [90.25-116.00], respectively. As the 90% CI of GMR were entirely within 80-125% for log-transformed parameters, two formulations were considered bioequivalent, in the extent and rate of absorption. Both formulations exhibited similar tolerability under fasting conditions.
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PMID:Bioequivalence evaluation of two marketed brands of stavudine 40 mg capsules in healthy human South African volunteers. 1545 72

Stavudine (STV, d4T, 2',3'-didehydro-3'-deoxythymidine, CAS 3056-17-5) is a standard anti-HIV drug. Stampidine (STAMP, DDE-113, HI-113, N-[p-(4-bromophenyl)-2',3'-didehydro-3'-deoxy-5'-thymidylyl]-L-alanine methyl ester, CAS 217178-62-6) is a novel aryl phosphate derivative of stavudine with more potent anti-HIV activity and more favorable pharmacodynamic features. The remarkable potency of stampidine against clinical HIV-1 isolates with NRTI- or NNRTI-resistance (NRTI, nucleoside reverse transcriptase inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitor) warrants the further development of this new anti-HIV agent.
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PMID:Stampidine as a novel nucleoside reverse transcriptase inhibit with potent anti-HIV activity. 1657 Aug 21

The arylphosphoramidate derivative of stavudine (STV, d4T, 2,3'-didehydro-3'-deoxythymidine, CAS 3056-17-5), stampidine (STAMP, DDE-113, HI-113, N-[p-(4-bromophenyl)-2',3'-didehydro-3'-deoxy-5'-thymidylyl]-L-alanine methyl ester, CAS 217178-62-6), is a novel anti-HIV agent. STAMP was prepared under current Good Manufacturing Practice (cGMP) conditions on the scale of kilograms. Solid STAMP was subsequently formulated as a capsule under GMP conditions for oral administration.
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PMID:Large-scale synthesis and formulation of GMP-grade stampidine, a new anti-HIV agent. 1657 Aug 22


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