Document 0010
 DOCN  M9590010
 TI    Anticytomegaloviral activity and safety of cidofovir in patients with
       human immunodeficiency virus infection and cytomegalovirus viruria.
 DT    9509
 AU    Polis MA; Spooner KM; Baird BF; Manischewitz JF; Jaffe HS; Fisher PE;
       Falloon J; Davey RT Jr; Kovacs JA; Walker RE; et al; National Institute
       of Allergy and Infectious Diseases, National; Institutes of Health,
       Bethesda, Maryland 20892, USA.
 SO    Antimicrob Agents Chemother. 1995 Apr;39(4):882-6. Unique Identifier :
       AIDSLINE MED/95305544
 AB    Cidofovir (HPMPC; (S)-1-[3-hydroxy-2-(phosphonylmethoxy)propyl]cytosine)
       is a nucleotide analog with activity against human cytomegalovirus
       (CMV). A phase I/II dose escalation trial was conducted with
       asymptomatic human immunodeficiency virus (HIV)-infected patients with
       CMV viruria to determine its pharmacokinetics, maximally tolerated dose,
       and preliminary antiviral activity against CMV. Qualitative CMV blood
       and urine cultures were monitored weekly to assess anti-CMV activity.
       Twenty-one HIV-infected persons with CD4 counts from 0 to 389 cells per
       microliters (median, 39) were enrolled in six dose-ranging groups. The
       first five groups enrolled four patients each to receive cidofovir
       infusions either weekly or biweekly for 4 weeks or every 3 weeks for 12
       weeks. The sixth group enrolled one patient who received infusions of 5
       mg/kg of body weight every other week. Patients receiving 0.5 or 1.5
       mg/kg twice weekly experienced no serious toxicity. The first two
       patients who received 5 mg/kg twice weekly developed glycosuria and 2+
       proteinuria. Subsequent patients received concomitant probenecid to
       attempt to ameliorate renal toxicity. Seventeen patients experienced
       proteinuria on one or more occasions; 6 of them experienced at least 2+
       proteinuria. Four patients did not complete the study as planned because
       of renal toxicity. Positive CMV urine cultures reverted to negative in 2
       of 8 patients receiving doses of < or = 1.5 mg/kg twice weekly and 11 of
       13 patients receiving higher doses. Cidofovir has in vivo anti-CMV
       activity demonstrated by prolonged clearing of CMV viruria, although
       this observation is tempered by the fact that clearance of viremia could
       not be demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)
 DE    Adult  Antiviral Agents/*THERAPEUTIC USE  Cytomegalovirus
       Infections/*DRUG THERAPY  Cytosine/*ANALOGS &
       DERIVATIVES/PHARMACOKINETICS/THERAPEUTIC USE  Human  HIV
       Infections/*DRUG THERAPY  Male  Middle Age  Organophosphorus
       Compounds/PHARMACOKINETICS/*THERAPEUTIC USE  Urine/MICROBIOLOGY  JOURNAL
       ARTICLE

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