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Titolo:
PHASE-I STUDY OF HIGH-DOSE, INTRAVENOUS RSCD4 IN SUBJECTS WITH ADVANCED HIV-1 INFECTION
Autore:
SCHACKER T; COLLIER AC; COOMBS R; UNADKAT JD; FOX I; ALAM J; WANG JP; EGGERT E; COREY L;
Indirizzi:
UNIV WASHINGTON,DEPT MED,MAIL STOP ZA22,325 9TH ST SEATTLE WA 98104 UNIV WASHINGTON,DEPT LAB MED SEATTLE WA 98195 UNIV WASHINGTON,DEPT MICROBIOL SEATTLE WA 98195 UNIV WASHINGTON,DEPT PHARMACEUT SEATTLE WA 98195 BIOGEN INC BOSTON MA 00000
Titolo Testata:
Journal of acquired immune deficiency syndromes and human retrovirology
fascicolo: 2, volume: 9, anno: 1995,
pagine: 145 - 152
SICI:
1077-9450(1995)9:2<145:PSOHIR>2.0.ZU;2-O
Fonte:
ISI
Lingua:
ENG
Soggetto:
RECOMBINANT SOLUBLE CD4; AIDS-RELATED COMPLEX; IMMUNODEFICIENCY-SYNDROME AIDS; NEUTRALIZATION; THERAPY; VIRIONS; VIREMIA; GP120;
Keywords:
RSCD4; HIV; VIREMIA; PHARMACOKINETICS; PHASE I STUDY; IC50; IC90;
Tipo documento:
Article
Natura:
Periodico
Citazioni:
18
Recensione:
Indirizzi per estratti:
Citazione:
T. Schacker et al., "PHASE-I STUDY OF HIGH-DOSE, INTRAVENOUS RSCD4 IN SUBJECTS WITH ADVANCED HIV-1 INFECTION", Journal of acquired immune deficiency syndromes and human retrovirology, 9(2), 1995, pp. 145-152

Abstract

In vitro, recombinant soluble CD4 (rsCD4) attaches to and inactivateshuman immunodeficiency virus (HIV). To determine if prolonged therapywith high-dose intravenous rsCD4 provides an in vivo benefit, we gavethree HIV-l-infected patients with AIDS, whose isolates were susceptible in vitro to rsCD4, 10 mg/kg of rsCD4 for 4 weeks, 5 mg/kg for 4 weeks, and 1 mg/kg for 2 weeks. Single-dose pharmacokinetic studies performed prior to this showed transient in vivo decreases of HIV-1 plasmaviremia in all three subjects. Surrogate markers of HIV activity, clinical status, HIV-I p24 antigen, plasma HIV-I titers, and peripheral blood mononuclear cell (PBMC) intracellular titers of virus were measured at entry, and every other week after onset of therapy, All subjectsdemonstrated rsCD4 concentration-dependent reduction in plasma viremia, with two subjects having complete neutralization of cell-free virus. The third subject's isolate was relatively resistant to the in vivo effects of rsCD4 and only partial reduction in plasma virus titers wasobtained, even at the highest dose of 10 mg/kg. There was no change in the PBMC intracellular viral titer or surrogate markers of HIV-1 activity (including CD4 cell count and beta(2)-microglobulin). There was subjective improvement in clinical symptoms, and all subjects gained weight with the highest doses of rsCD4. rsCD4 exhibited linear pharmacokinetics over the dose range studied. We conclude that high-dose intravenous rsCD4 can be safely given for up to 10 weeks and that it has a stable pharmacokinetic profile. Subjects with uniquely susceptible isolates show a consistent, dose-dependent reduction of infectious HIV-1 titer for up to 8 hours. However, two or three times per day dosing may be required to demonstrate a prolonged effect on HIV-1 replication. It appears that sustained high levels of rsCD4 are safe and offer the potential of achieving significant antiviral effects.

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Documento generato il 04/12/20 alle ore 16:25:47