Phase I study of combination therapy with intravenous cidofovir and oral ganciclovir for cytomegalovirus retinitis in patients with AIDS.
Ganciclovir and cidofovir, two antiviral agents used in the treatment of cytomegalovirus (CMV) retinitis, have a synergistic effect inhibiting CMV replication in vitro. In a phase I study, seven patients with AIDS-related CMV retinitis were treated with cidofovir (5 mg/kg intravenously every 2 weeks) combined with ganciclovir (1 g orally three times a day). During a median of 5.5 months (range, 1-12 months) of combined therapy, only one patient had retinitis progression, and only two of 28 blood cultures (specimens of which were obtained on a monthly basis) yielded CMV. Dose-limiting adverse ocular effects (anterior uveitis [two patients] and hypotony [two patients]) occurred in three of seven patients. The results suggest that combination therapy with intravenous cidofovir and oral ganciclovir (a regimen that does not require indwelling central venous catheter access) might enhance clinical efficacy. Less frequent administration of cidofovir in combination with oral ganciclovir should be prospectively studied to determine if the incidence of treatment-associated toxicity might be reduced.
Jacobson
M A
MA
Department of Medicine AIDS Program, University of California at San Francisco, USA. mjacobson@sfaids.ucsf.edu
Wilson
S
S
Stanley
H
H
Holtzer
C
C
Cherrington
J
J
Safrin
S
S
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy*; D000328:Adult; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000077404:Cidofovir; D017726:Cytomegalovirus Retinitis / Q000188:drug therapy*; D003596:Cytosine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D015774:Ganciclovir / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D000998:Antiviral Agents; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D003596:Cytosine; D000077404:Cidofovir; D015774:Ganciclovir