Treatment of advanced human immunodeficiency virus type 1 disease with the viral entry inhibitor PRO 542.

Abstract:

:Viral entry inhibitors represent an emerging mode of therapy for human immunodeficiency virus type 1 (HIV-1) infection. PRO 542 (CD4-immunoglobulin G2) is a tetravalent CD4-immunoglobulin fusion protein that broadly neutralizes primary HIV-1 isolates. PRO 542 binds to the viral surface glycoprotein gp120 and blocks attachment and entry of virus into CD4(+) cells. Previously, PRO 542 demonstrated antiviral activity without significant toxicity when tested at single doses ranging to 10 mg/kg. In this study, 12 HIV-infected individuals were treated with 25-mg/kg single-dose PRO 542 and then monitored for safety, antiviral effects, and PRO 542 pharmacokinetics for 6 weeks. The study examined two treatment cohorts that differed in the extent of HIV-1 disease progression. PRO 542 at 25 mg/kg was well tolerated and demonstrated a serum half-life of 3 days. Statistically significant acute reductions in HIV-1 RNA levels were observed across all study patients, and greater antiviral effects were observed in the cohort of patients with more advanced HIV-1 disease. In advanced disease (HIV-1 RNA > 100,000 copies/ml; CD4 lymphocytes < 200 cells/mm(3)), PRO 542 mediated an 80% response rate and statistically significant approximately 0.5 log(10) mean reductions in viral load for 4 to 6 weeks posttreatment. Similar findings were obtained in an analysis of all (n = 11) advanced disease patients treated to date with single doses of PRO 542 ranging from 1 to 25 mg/kg. In addition, a significant correlation was observed between antiviral effects observed in vivo and viral susceptibility to PRO 542 in vitro. The findings support continued development of PRO 542 for salvage therapy of advanced HIV-1 disease.

authors

Jacobson JM,Israel RJ,Lowy I,Ostrow NA,Vassilatos LS,Barish M,Tran DN,Sullivan BM,Ketas TJ,O'Neill TJ,Nagashima KA,Huang W,Petropoulos CJ,Moore JP,Maddon PJ,Olson WC

doi

10.1128/aac.48.2.423-429.2004

subject

Has Abstract

pub_date

2004-02-01 00:00:00

pages

423-9

issue

2

eissn

0066-4804

issn

1098-6596

journal_volume

48

pub_type

临床试验,杂志文章
  • Synergy between efflux pump CmeABC and modifications in ribosomal proteins L4 and L22 in conferring macrolide resistance in Campylobacter jejuni and Campylobacter coli.

    abstract::Macrolide-resistant mutants of Campylobacter jejuni and Campylobacter coli were selected in vitro using erythromycin and tylosin. These mutants exhibited modifications in the ribosomal proteins L4 (G74D) and L22 (insertions at position 86 or 98). A synergy between the CmeABC efflux pump and these modifications in conf...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00616-06

    authors: Cagliero C,Mouline C,Cloeckaert A,Payot S

    更新日期:2006-11-01 00:00:00

  • Comparative activities of several nucleoside analogs against influenza A, B, and C viruses in vitro.

    abstract::A set of 20 nucleoside analogs were examined for their inhibitory effects on the cytopathogenicity and growth of influenza virus type A, B, and C strains in Madin-Darby canine kidney (MDCK) cells. Among the compounds evaluated, pyrazofurin, 3-deazaguanine, ribavirin, carbodine, and cyclopentenyl cytosine inhibited vir...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.32.6.906

    authors: Shigeta S,Konno K,Yokota T,Nakamura K,De Clercq E

    更新日期:1988-06-01 00:00:00

  • Prevention of experimental endotoxin shock by a monocyte activator.

    abstract::In patients with polytrauma or major surgery, severe bacterial infections leading to septic shock and multiorgan failure are still a major cause of death. Prevention of septic shock in patients at risk would be an alternative to treatment of patients with overt septic shock. We therefore conducted a trial with the mon...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.39.11.2535

    authors: Passlick B,Labeta MO,Izbicki JR,Ostertag P,Löffler T,Siebeck M,Pichlmeier U,Schweiberer L,Ziegler-Heitbrock HW

    更新日期:1995-11-01 00:00:00

  • Human immunodeficiency virus inhibition is prolonged by 3'-azido-3'-deoxythymidine alternating with 2',3'-dideoxycytidine compared with 3'-azido-3'-deoxythymidine alone.

    abstract::The inhibition of the lymphadenopathy-associated virus strain of human immunodeficiency virus (HIV) by alternating regimens of two dideoxynucleosides, 3'-azido-3'-deoxythymidine (AZT) (zidovudine) and 2',3'-dideoxycytidine (ddC), was determined in CEM cells. Cultures infected with virus for 2 h were treated with clini...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.33.6.920

    authors: Spector SA,Ripley D,Hsia K

    更新日期:1989-06-01 00:00:00

  • Efficacy of nitazoxanide against Cryptosporidium parvum in cell culture and in animal models.

    abstract::Nitazoxanide (NTZ), a drug currently being tested in human clinical trials for efficacy against chronic cryptosporidiosis, was assessed in cell culture and in two animal models. The inhibitory activity of NTZ was compared with that of paromomycin (PRM), a drug that is partially effective against Cryptosporidium parvum...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.42.8.1959

    authors: Theodos CM,Griffiths JK,D'Onfro J,Fairfield A,Tzipori S

    更新日期:1998-08-01 00:00:00

  • Selection of clarithromycin-resistant Mycobacterium avium complex during combined therapy using the beige mouse model.

    abstract::Sixteen weeks of treatment with clarithromycin (CLARI) alone displayed significant bactericidal activity against Mycobacterium avium complex infection in beige mice. Only two combined regimens, CLARI combined with an initial 4 or 8 weeks of amikacin (AMIKA), displayed activity greater than that displayed by CLARI alon...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.39.3.608

    authors: Lounis N,Ji B,Truffot-Pernot C,Grosset J

    更新日期:1995-03-01 00:00:00

  • Artifactual depression of serum glutamic oxaloacetic transaminase by metronidazole.

    abstract::Eighteen patients developed abnormally low serum glutamic oxaloacetic transaminase values during metronidazole therapy. Metronidazole absorbs at 340 nm, simulating reduced nicotinamide adenine dinucleotide, which is the final colorimetric product of the serum glutamic oxaloacetic transaminase assay. ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.14.4.636

    authors: Rissing JP,Newman C,Moore WL Jr

    更新日期:1978-10-01 00:00:00

  • In vitro induction of human immunodeficiency virus type 1 variants resistant to 2'-beta-Fluoro-2',3'-dideoxyadenosine.

    abstract::2'-beta-Fluoro-2',3'-dideoxyadenosine (F-ddA) is an acid-stable purine dideoxynucleoside analog active against a wide spectrum of human immunodeficiency virus type 1 (HIV-1) and HIV-2 strains in vitro. F-ddA is presently undergoing a phase I clinical trial at the National Cancer Institute. We induced HIV-1 variants re...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.41.6.1313

    authors: Tanaka M,Srinivas RV,Ueno T,Kavlick MF,Hui FK,Fridland A,Driscoll JS,Mitsuya H

    更新日期:1997-06-01 00:00:00

  • Effects of dihydrostreptomycin on ribosome function in vivo: lack of correlation between changes in ribosome patterns and growth.

    abstract::In vivo treatment of susceptible Escherichia coli cultures with low concentrations of dihydrostreptomycin leads to a decline in polysomes and a corresponding increase in 70S particles which behave as run-off ribosomes, as well as free 30S and 50S subunits. We have examined the timing and extent of these effects on rib...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.7.3.341

    authors: Kogut M,Prizant E

    更新日期:1975-03-01 00:00:00

  • In vitro efficacy of sulbactam combined with ampicillin against anaerobic bacteria.

    abstract::An ampicillin-sulbactam combination was compared with ampicillin alone, chloramphenicol, clindamycin, and metronidazole against 272 strains of anaerobic bacteria. Chloramphenicol and ampicillin-sulbactam were the most effective, inhibiting 98 to 99% of strains tested at breakpoint (16 micrograms/ml). The combination o...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.27.5.876

    authors: Wexler HM,Harris B,Carter WT,Finegold SM

    更新日期:1985-05-01 00:00:00

  • Isolation of trimethoprim-resistant, sulfonamide-susceptible Enterobacteriaceae from urinary tract infections.

    abstract::The isolation of trimethoprim-resistant, sulfonamide-susceptible Enterobacteriaceae causing urinary tract infections is reported. The appearance of these strains followed the introduction of trimethoprim alone for use as treatment. Trimethoprim resistance was attributable to plasmids or transposons less frequently in ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.23.4.617

    authors: Towner KJ,Smith MA,Cowlishaw WA

    更新日期:1983-04-01 00:00:00

  • Relevance of in vitro antimicrobial susceptibility of Brucella melitensis to relapse rate in human brucellosis.

    abstract::The in vitro susceptibility of Brucella melitensis was examined vis-a-vis the clinical outcome in 75 patients with brucellosis. The initial MICs for Brucella isolates from patients who relapsed and from those who did not were similar. Furthermore, the MICs for isolates from patients whose infections relapsed were no d...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.30.6.958

    authors: Ariza J,Bosch J,Gudiol F,Liñares J,Viladrich PF,Martín R

    更新日期:1986-12-01 00:00:00

  • Biosynthetic studies on antibiotic A47934.

    abstract::A47934, a peptide antibiotic produced by Streptomyces toyocaensis, belongs to the glycopeptide class of compounds which includes ristocetin and vancomycin. Incorporation studies with radioisotope-labeled substrates indicated that tyrosine, p-hydroxyphenylglycine, p-hydroxyphenylglyoxylate, acetate, and sulfate were ef...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.31.10.1497

    authors: Zmijewski MJ Jr,Briggs B,Logan R,Boeck LD

    更新日期:1987-10-01 00:00:00

  • In vitro activities of benflumetol against 158 Senegalese isolates of Plasmodium falciparum in comparison with those of standard antimalarial drugs.

    abstract::The 50% inhibitory concentration (IC50s) of benflumetol (range, 12.5 to 240 nM; mean, 55.1 nM) for 158 Senegalese isolates were evaluated. Ten isolates (6%) showed decreased susceptibility to benflumetol. Benflumetol was slightly more potent against chloroquine-resistant isolates (P < 0.025). No correlation or weak co...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.43.2.418

    authors: Pradines B,Tall A,Fusai T,Spiegel A,Hienne R,Rogier C,Trape JF,Le Bras J,Parzy D

    更新日期:1999-02-01 00:00:00

  • Susceptibility of drug-resistant clinical herpes simplex virus type 1 strains to essential oils of ginger, thyme, hyssop, and sandalwood.

    abstract::Acyclovir-resistant clinical isolates of herpes simplex virus type 1 (HSV-1) were analyzed in vitro for their susceptibilities to essential oils of ginger, thyme, hyssop, and sandalwood. All essential oils exhibited high levels of virucidal activity against acyclovir-sensitive strain KOS and acyclovir-resistant HSV-1 ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00426-06

    authors: Schnitzler P,Koch C,Reichling J

    更新日期:2007-05-01 00:00:00

  • Copper(II)-Bis(Thiosemicarbazonato) Complexes as Antibacterial Agents: Insights into Their Mode of Action and Potential as Therapeutics.

    abstract::There is increasing interest in the use of lipophilic copper (Cu)-containing complexes to combat bacterial infections. In this work, we showed that Cu complexes with bis(thiosemicarbazone) ligands [Cu(btsc)] exert antibacterial activity against a range of medically significant pathogens. Previous work using Neisseria ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01289-15

    authors: Djoko KY,Goytia MM,Donnelly PS,Schembri MA,Shafer WM,McEwan AG

    更新日期:2015-10-01 00:00:00

  • Inhibition of mouse LM cell replication by trifluorothymidine: role of cytosolic deoxythymidine kinase.

    abstract::The effects of trifluorothymidine (5-trifluoromethyl-2'-deoxyuridine, F3dThd) on the replication of three mouse cell lines, LM929, Ltk- (and LM929 derivative devoid of cytosolic deoxythymidine [dThd] kinase activity), and Ltk- c139 (a Ltk- derivative which expresses herpes simplex virus type 1-specified dThd kinase su...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.19.5.881

    authors: Wigdahl BL,Parkhurst JR

    更新日期:1981-05-01 00:00:00

  • Itraconazole resistance in Aspergillus fumigatus.

    abstract::Invasive aspergillosis is an increasingly frequent opportunistic infection in immunocompromised patients. Only two agents, amphotericin B and itraconazole, are licensed for therapy. Itraconazole acts through inhibition of a P-450 enzyme undertaking sterol 14alpha demethylation. In vitro resistance in Aspergillus fumig...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.41.6.1364

    authors: Denning DW,Venkateswarlu K,Oakley KL,Anderson MJ,Manning NJ,Stevens DA,Warnock DW,Kelly SL

    更新日期:1997-06-01 00:00:00

  • Antiviral activity of a phosphorothioate oligonucleotide complementary to RNA of the human cytomegalovirus major immediate-early region.

    abstract::Phosphorothioate oligonucleotides complementary to mRNA of the human cytomegalovirus (HCMV) DNA polymerase gene or to RNA transcripts of the major immediate-early regions 1 and 2 (IE1 and IE2) of HCMV were evaluated for antiviral activity in a 96-well immunoassay with primary human dermal fibroblasts as host cells. Ol...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.37.9.1945

    authors: Azad RF,Driver VB,Tanaka K,Crooke RM,Anderson KP

    更新日期:1993-09-01 00:00:00

  • Comparative effect of protein binding on the killing activities of teicoplanin and vancomycin.

    abstract::The effect of protein binding on the activity of teicoplanin against Staphylococcus aureus was evaluated. Bactericidal rates of teicoplanin in cation-supplemented Mueller-Hinton broth (SMHB) and in a 1:1 mixture of pooled human serum and cation-supplemented Mueller-Hinton broth (PHS-SMHB) were compared with those of v...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1128/aac.35.6.1089

    authors: Bailey EM,Rybak MJ,Kaatz GW

    更新日期:1991-06-01 00:00:00

  • Relationship of carbapenem restriction in 22 university teaching hospitals to carbapenem use and carbapenem-resistant Pseudomonas aeruginosa.

    abstract::Many hospital antimicrobial stewardship programs restrict the availability of selected drugs by requiring prior approval. Carbapenems may be among the restricted drugs, but it is unclear if hospitals that restrict availability actually use fewer carbapenems than hospitals that do not restrict use. Nor is it clear if r...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章,多中心研究

    doi:10.1128/AAC.01535-08

    authors: Pakyz AL,Oinonen M,Polk RE

    更新日期:2009-05-01 00:00:00

  • Biliary concentrations of piperacillin in patients undergoing cholecystectomy.

    abstract::Piperacillin is a new semisynthetic, expanded-spectrum penicillin with marked activity against Pseudomonas aeruginosa. The biliary excretion of piperacillin was studied in patients undergoing cholecystectomy. Concentrations of piperacillin in common duct bile at 35 to 90 min postinfusion of 1-g doses ranged from 31 to...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.19.2.309

    authors: Giron JA,Meyers BR,Hirschman SZ

    更新日期:1981-02-01 00:00:00

  • Use of adjuvants for enhancement of rectal absorption of cefoxitin in humans.

    abstract::The biological availability of cefoxitin administered rectally in the form of suppositories was examined in six human subjects by a cross-over design. Four different suppository systems containing adjuvants expected to enhance the absorption of the drug were studied. The presence of sodium salicylate and a nonionic su...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1128/aac.28.2.211

    authors: Davis SS,Burnham WR,Wilson P,O'Brien J

    更新日期:1985-08-01 00:00:00

  • Pharmacokinetics of clarithromycin and zidovudine in patients with AIDS.

    abstract::The interrelationships between the pharmacokinetics of zidovudine alone and of zidovudine plus clarithromycin were evaluated with 18 volunteers with AIDS who had no infection with Mycobacterium avium complex or clinical evidence of gastroenteritis. Patients received 200 mg of zidovudine orally every 8 h on days 1 to 4...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 临床试验,杂志文章

    doi:10.1128/aac.39.6.1355

    authors: Vance E,Watson-Bitar M,Gustavson L,Kazanjian P

    更新日期:1995-06-01 00:00:00

  • Comparative in vitro studies of nalidixic acid, oxolinic acid, and a new analog with thieno (2,3-b) pyridine structure.

    abstract::Bacterial susceptibility to a new organic acid related to nalidixic acid and oxolinic acid was tested. The in vitro susceptibility pattern of the new compound was found to be very similar to that of nalidixic acid. ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.13.3.533

    authors: Gilis PM,Haemers A,Pattyn SR

    更新日期:1978-03-01 00:00:00

  • In vitro assessment of the effect of clavulanic acid at concentrations achieved in human serum on the bactericidal activity of amoxicillin at physiological concentrations against Staphylococcus aureus: implications for dosage regimens.

    abstract::The effects on Staphylococcus aureus viability and beta-lactamase activity of concentrations that simulated those in human serum after a combined dose of 875 mg of amoxicillin and 125 mg of clavulanic acid were studied in an in vitro pharmacodynamic model. Six hours of preexposure to concentrations of the amoxicillin-...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.41.6.1403

    authors: Aguilar L,Martín M,Balcabao IP,Gómez-Lus ML,Dal-Ré R,Prieto J

    更新日期:1997-06-01 00:00:00

  • Tetracycline resistance and tetM in pathogenic urogenital bacteria.

    abstract::Clinical isolates of Gardnerella vaginalis, Streptococcus agalactiae, Bacteroides spp., and Mobiluncus spp. were screened for resistance to tetracycline and for the presence of the streptococcal tetM determinant. The S. agalactiae and G. vaginalis strains contained DNA sequences homologous to the tetM determinant, whi...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.30.5.810

    authors: Roberts MC,Hillier SL,Hale J,Holmes KK,Kenny GE

    更新日期:1986-11-01 00:00:00

  • International interlaboratory quality control program for measurement of antiretroviral drugs in plasma.

    abstract::An international interlaboratory quality control program for measurement of antiretroviral drugs was initiated. The first round was confined to protease inhibitors and showed large variability in the performance of participating laboratories. The results demonstrate the need for and utility of an ongoing quality contr...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.46.3.884-886.2002

    authors: Aarnoutse RE,Verweij-van Wissen CP,van Ewijk-Beneken Kolmer EW,Wuis EW,Koopmans PP,Hekster YA,Burger DM

    更新日期:2002-03-01 00:00:00

  • Identification of a Novel Gene Associated with High-Level β-Lactam Resistance in Heterogeneous Vancomycin-Intermediate Staphylococcus aureus Strain Mu3 and Methicillin-Resistant S. aureus Strain N315.

    abstract::β-Lactam resistance levels vary among methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates, mediated by chromosomal mutations and exogenous resistance gene mecA However, MRSA resistance mechanisms are incompletely understood. A P440L mutation in the RNA polymerase β' subunit (RpoC) in slow-vancomycin-i...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00712-18

    authors: Matsuo M,Yamamoto N,Hishinuma T,Hiramatsu K

    更新日期:2019-01-29 00:00:00

  • RmtF, a new member of the aminoglycoside resistance 16S rRNA N7 G1405 methyltransferase family.

    abstract::Multidrug-resistant clinical isolate Klebsiella pneumoniae BM4686 was highly resistant to 4,6-disubstituted 2-deoxystreptamines and to fortimicin. Resistance was due to the presence, on the 40-kb non-self-transferable plasmid pIP849, of the rmtF gene which was cotranscribed with the upstream aac(6')-Ib gene. The deduc...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00660-12

    authors: Galimand M,Courvalin P,Lambert T

    更新日期:2012-07-01 00:00:00