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Reviews of Infectious Diseases 1990Treatment of cytomegalovirus (CMV) disease met with limited success until the development of ganciclovir. Favorable clinical responses to ganciclovir have been reported... (Review)
Review
Treatment of cytomegalovirus (CMV) disease met with limited success until the development of ganciclovir. Favorable clinical responses to ganciclovir have been reported in approximately 80% of immunocompromised patients with CMV retinitis or gastrointestinal disease. CMV pneumonia is more difficult to treat, with therapy benefiting 10%-72% of patients. Ganciclovir must be given parenterally; the dose-limiting adverse event is neutropenia. Patients with AIDS frequently experience relapse and require maintenance therapy. Foscarnet is an attractive anti-CMV drug but must be given parenterally and is completely dependent on renal clearance for elimination. Prevention of CMV disease with antiviral drugs may be possible. Five weeks of intravenous acyclovir (500 mg/m2 three times a day) significantly reduced the risk of CMV infection and disease in seropositive allogeneic bone marrow transplant recipients. The prophylactic benefit of acyclovir has recently been confirmed and extended by a placebo-controlled trial in renal allograft recipients at the University of Minnesota. A 12-week course of high doses of oral acyclovir (3,200 mg/d) was safe and significantly reduced the incidence of CMV infection and disease.
Topics: Acyclovir; Antiviral Agents; Cytomegalovirus Infections; Foscarnet; Ganciclovir; Humans; Phosphonoacetic Acid; Pyrimidine Nucleosides; Vidarabine
PubMed: 2173114
DOI: 10.1093/clinids/12.supplement_7.s849 -
The American Journal of Nursing Oct 1991
Clinical Trial Randomized Controlled Trial
Topics: Acquired Immunodeficiency Syndrome; Antiviral Agents; Cytomegalovirus Infections; Foscarnet; Ganciclovir; Humans; Phosphonoacetic Acid; Retinitis
PubMed: 1654745
DOI: 10.1097/00000446-199110000-00005 -
Journal of Chromatography Mar 1989
Topics: Chromatography, Ion Exchange; Organophosphorus Compounds; Phosphonoacetic Acid; Technetium
PubMed: 2745635
DOI: 10.1016/s0378-4347(00)82970-9 -
Lancet (London, England) May 1985
Topics: Adult; Cytomegalovirus Infections; Foscarnet; Humans; Male; Organophosphorus Compounds; Phosphonoacetic Acid; Pneumonia, Viral
PubMed: 2860348
DOI: 10.1016/s0140-6736(85)92447-x -
Lancet (London, England) Jan 1989
Topics: Acquired Immunodeficiency Syndrome; Adult; Antiviral Agents; Cytomegalovirus Infections; Drug Administration Schedule; Foscarnet; Home Care Services; Humans; Infusions, Intravenous; Male; Organophosphorus Compounds; Phosphonoacetic Acid; Retinitis
PubMed: 2563066
DOI: 10.1016/s0140-6736(89)91167-7 -
Journal of the American Chemical Society Jan 2003Phosphonoacetate and thiophosphonoacetate oligodeoxynucleotides were prepared via a solid-phase synthesis strategy. Under Reformatsky reaction conditions, novel...
Phosphonoacetate and thiophosphonoacetate oligodeoxynucleotides were prepared via a solid-phase synthesis strategy. Under Reformatsky reaction conditions, novel esterified acetic acid phosphinodiamidites were synthesized and condensed with appropriately protected 5'-O-(4, 4'-dimethoxytrityl)-2'-deoxynucleosides to yield 3'-O-phosphinoamidite reactive monomers. These synthons when activated with tetrazole were used with an automated DNA synthesizer to prepare phosphonoacetic acid modified internucleotide linkages on controlled pore glass. The phosphinoacetate coupling products were quantitatively oxidized at each step with (1S)-(+)-(10-camphorsulfonyl)oxaziridine or 3H-1,2-benzodithiol-3-one-1,1-dioxide to produce mixed sequence phosphonoacetate and thiophosphonoacetate oligodeoxynucleotides with an average per cycle coupling efficiency of greater than 97%. Completely deprotected, modified oligodeoxynucleotides were purified by reverse-phase HPLC and characterized by ion exchange HPLC, (31)P NMR, and MALDI/TOF mass spectroscopy. Both analogues were stable toward hydrolysis with snake venom phosphodiesterase and stimulated RNase H1 activity.
Topics: Chromatography, High Pressure Liquid; Chromatography, Ion Exchange; Nuclear Magnetic Resonance, Biomolecular; Oligonucleotides; Organothiophosphates; Phosphonoacetic Acid; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
PubMed: 12537492
DOI: 10.1021/ja027983f -
International Ophthalmology Clinics 1989
Review
Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Cytomegalovirus Infections; Diabetic Retinopathy; Diagnosis, Differential; Foscarnet; Ganciclovir; Humans; Phosphonoacetic Acid; Pneumonia, Pneumocystis; Prognosis; Retinal Diseases; Retinitis; Zidovudine
PubMed: 2541095
DOI: 10.1097/00004397-198902920-00008 -
Reviews of Infectious Diseases 1988Retinitis is the commonest clinical manifestation of cytomegalovirus (CMV) infection in patients with AIDS. Untreated patients generally experience progressive... (Review)
Review
Retinitis is the commonest clinical manifestation of cytomegalovirus (CMV) infection in patients with AIDS. Untreated patients generally experience progressive involvement of the retina, which may result in blindness. Attempts to treat this condition with vidarabine and interferon-alpha have been uniformly unsuccessful. Therapy with ganciclovir (9[(1,3-dihydroxy-2-propoxy)methyl]guanine) (7.5-15 mg/[kg./d] given intravenously in two or three divided doses) has been shown to halt progression of retinitis and may result in limited healing in some cases; viremia and shedding of virus from other sites (such as the urine) are halted or reduced. However, reactivation of infection and retinitis usually occurs when ganciclovir therapy is discontinued. For that reason, most patients have received continued therapy with the drug, most commonly at a dosage of 5-6 mg/(kg.d) administered as a single intravenous infusion 5-7 days per week. Both retrospective and prospective, randomized trials have shown that maintenance therapy delays (but does not prevent) reactivation of infection. Much more limited studies with foscarnet (trisodium phosphonoformate) suggest that this drug will also be useful for treatment of CMV retinitis in AIDS patients. Further research is needed, however, since existing agents have a low therapeutic ratio and cannot be given orally to patients requiring long-term maintenance therapy.
Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Antiviral Agents; Cytomegalovirus Infections; Foscarnet; Ganciclovir; Humans; Phosphonoacetic Acid; Retinitis
PubMed: 2847289
DOI: 10.1093/clinids/10.supplement_3.s522 -
Journal of Acquired Immune Deficiency... 1991Both ganciclovir, a nucleoside analogue, and foscarnet, a pyrophosphate analogue, specifically bind cytomegalovirus (CMV) DNA polymerase and inhibit CMV replication at... (Review)
Review
Both ganciclovir, a nucleoside analogue, and foscarnet, a pyrophosphate analogue, specifically bind cytomegalovirus (CMV) DNA polymerase and inhibit CMV replication at plasma concentrations achievable with intravenous administration. The agents have similar plasma half-lives, and both are cleared solely by the kidneys. Foscarnet has a low solubility and a high degree of ionization at physiologic pH, requiring it to be administered in higher doses and larger volumes. Both drugs are administered as an initial induction regimen followed by a long-term maintenance regimen. Among patients with the acquired immune deficiency syndrome (AIDS) who have CMV retinitis, the efficacy of long-term maintenance therapy, as measured by median time to retinitis progression, appears to be similar for the two drugs. The major toxicity of ganciclovir is myelosuppression, with dose-limiting neutropenia occurring in approximately 16% and thrombocytopenia in 5% of AIDS patients. The major toxicity of foscarnet is nephrotoxicity, with dose-limiting toxicity occurring in approximately 10-23% of patients; other effects of foscarnet include hypocalcemia, which may be associated with seizure and arrhythmia. Studies in vitro indicate an additive or synergistic inhibitory effect on CMV when these two drugs are combined, suggesting that lower-dose combination regimens or higher-dose alternating regimens may result in greater efficacy with less toxicity than with either drug alone.
Topics: Antiviral Agents; Cytomegalovirus Infections; Drug Therapy, Combination; Eye Infections, Viral; Foscarnet; Ganciclovir; HIV Infections; Humans; Opportunistic Infections; Phosphonoacetic Acid; Retinitis
PubMed: 1848616
DOI: No ID Found -
Clinics in Dermatology 1989
Review
Topics: Acyclovir; Administration, Oral; Antiviral Agents; Female; Foscarnet; Herpes Genitalis; Humans; Interferons; Male; Papilloma; Phosphonoacetic Acid; Recurrence
PubMed: 2478279
DOI: 10.1016/0738-081x(89)90009-6