sorivudine and AIDS-Related-Opportunistic-Infections

The present randomized, double-blind, placebo-controlled, multicenter clinical trial was designed to compare the efficacy and tolerability of sorivudine [1-beta-D-arabinofuranosyl-E-(2-bromovinyl)uracil] and acyclovir for the treatment of dermatomal herpes zoster in human immunodeficiency virus (HIV)-seropositive patients. A total of 170 HIV-seropositive adults presenting with herpes zoster (confirmed by direct fluorescent-antigen testing and/or viral culture) were enrolled and randomized to receive a 10-day course of orally administered sorivudine (40 mg once daily plus acyclovir placebos) or acyclovir (800 mg five times daily plus sorivudine placebo). Patients were monitored daily to document the events of cutaneous healing, pain, zoster-related complications, and drug-related adverse events. Patients were reassessed on days 21 and 28 and then once monthly for 1 year. The primary efficacy endpoint was time to the cessation of new vesicle formation. Secondary efficacy endpoints included times to other events of cutaneous healing, resolution of pain, and frequency of dissemination and zoster recurrence. In a multivariate analysis, sorivudine was superior to acyclovir for reducing the times to the cessation of new vesicle formation (relative risk [RR] = 1.54, 95% confidence interval [CI] = 1.00 to 2.36; P = 0.049) and total lesion crusting (RR = 1.48, 95% CI = 1.07 to 2.04; P = 0.017). In a univariate analysis, there was a trend favoring sorivudine for the cessation of new vesicle formation (median of 3 versus 4 days; P = 0.07) and a significant advantage for time to total lesion crusting (median of 7 versus 8 days; P = 0.02). The time to the resolution of zoster-associated pain, the frequency of dissemination, and the frequency of zoster recurrence were not different between the two treatment groups. Both drugs were well tolerated. Sorivudine is an effective drug for the treatment of herpes zoster in HIV-infected patients and results in accelerated cutaneous healing when compared with acyclovir therapy.

Topics: Acyclovir; Adolescent; Adult; Aged; AIDS-Related Opportunistic Infections; Antiviral Agents; Arabinofuranosyluracil; Double-Blind Method; Female; Herpes Zoster; Humans; Male; Middle Aged; Quality of Life; Recurrence; Treatment Outcome

We report on the case of a 23-year-old female who presented with ocular signs of progressive outer retinal necrosis (PORN) syndrome and who failed to respond to acyclovir, ganciclovir, foscarnet and oral sorivudine.. The patient was treated with the antiviral drugs acyclovir, ganciclovir, foscarnet and oral sorivudine.. The patient failed to respond to a combination of antiviral drugs. Unfortunately, progression of the retintis occurred, which led to blindness.. Despite new drugs, the prognosis of PORN is poor and recurrence is common.

Topics: Adult; AIDS-Related Opportunistic Infections; Antibodies, Viral; Antiviral Agents; Arabinofuranosyluracil; Blindness; DNA, Viral; Drug Therapy, Combination; Female; Follow-Up Studies; Herpes Zoster Ophthalmicus; Herpesvirus 3, Human; Humans; Recurrence; Retinal Necrosis Syndrome, Acute; Treatment Failure

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Arabinofuranosyluracil; Chickenpox; Drug Resistance, Microbial; Female; Ganciclovir; Herpesvirus 3, Human; Humans; Retinal Necrosis Syndrome, Acute

Topics: Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Arabinofuranosyluracil; Chickenpox; Drug Resistance; Herpesvirus 3, Human; Humans; Male

We examined a patient with progressive outer retinal necrosis, which is presumably caused by the varicella-zoster virus in patients with the acquired immunodeficiency syndrome.. The patient was successfully treated with a combination of intravitreal ganciclovir and oral sorivudine. Treatment for progressive outer retinal necrosis has been disappointing; both acyclovir and ganciclovir have had only limited success. Sorivudine, a new antiviral medication with activity against varicella-zoster virus, may represent an effective alternative treatment for retinal necrosis.

Topics: AIDS-Related Opportunistic Infections; Antiviral Agents; Arabinofuranosyluracil; Drug Therapy, Combination; Ganciclovir; Herpes Zoster Ophthalmicus; Humans; Male; Middle Aged; Retinal Necrosis Syndrome, Acute

Patients with AIDS often experience recurrent infections with varicella-zoster virus (VZV) requiring repeated or prolonged treatment with acyclovir (ACV), which may lead to the development of ACV resistance. The ACV resistance of isolates recovered from such patients is associated with diminished VZV thymidine kinase (TK) function. We determined the nucleotide sequences of the TK genes of 12 ACV-resistant VZV strains purified from nine patients with AIDS. Five VZV strains contained nucleotide deletions in their TK genes, introducing a premature termination codon which is expected to result in the production of a truncated protein. No detectable full-length TK protein could be immunoprecipitated from extracts of cells infected with these virus strains. These TK-deficient strains were cross resistant to the TK-dependent antiviral agents ACV, 9-(4-hydroxy-3-hydroxymethylbutyl-yl)guanine (penciclovir), and 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl) uracil (BVaraU). The remaining seven strains each contained a nucleotide change that resulted in an amino acid substitution in the TK protein. These substitutions occurred throughout the TK protein, namely, in the ATP-binding site, the nucleoside-binding site, between the two binding sites, and at the carboxy terminus of the protein. We determined the effects of these mutations on the stability of TK protein expression in virus-infected cells and on the sensitivity of mutants to the TK-dependent antiviral agents ACV, BVaraU, and penciclovir.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; AIDS-Related Opportunistic Infections; Amino Acid Sequence; Antiviral Agents; Arabinofuranosyluracil; Base Sequence; Drug Resistance, Microbial; Genes, Viral; Genetic Variation; Guanine; Herpesviridae Infections; Herpesvirus 3, Human; Humans; Molecular Sequence Data; Mutagenesis; Precipitin Tests; Sequence Analysis; Sequence Homology, Amino Acid; Thymidine Kinase; Viral Plaque Assay