High dose oral ganciclovir treatment for cytomegalovirus retinitis.

Abstract

BACKGROUND:

The oral formulation of ganciclovir is approved at a dose of 3.0 g/day for maintenance treatment of cytomegalovirus (CMV) retinitis following an initial induction course of intravenous (IV) anti-CMV therapy. Median time to progression of CMV retinitis is 12-20 days shorter with oral compared to IV ganciclovir maintenance, likely due to the limited oral bioavailability of ganciclovir.

OBJECTIVES:

We hypothesized that higher systemic drug exposures associated with increased doses of oral ganciclovir would be associated with increased efficacy.

STUDY DESIGN:

Maintenance treatment of CMV retinitis with higher than standard doses of oral ganciclovir (>3.0 g/day) was studied in 281 AIDS patients with previously treated, stable retinitis randomized to 3.0, 4.5 or 6.0 g/day oral, or 5 m/kg/day IV ganciclovir. Graders unaware of treatment assignments determined retinitis progression using fundus photographs. Vision, other ophthalmic measures and safety were assessed open-label.

RESULTS:

Median days to photographic progression were 41, 50, 57 and 70, respectively (P=0.052; 3.0 g vs. IV). Hazard ratios for progression relative to IV were 1.66, 1.28 and 1.19 (P=0.016 for 3.0 g). NONMEM-modeled estimates of average serum ganciclovir concentration area under the curve (AUC(0-24)) correlated best with time to progression (P=0.0019). Six grams per day oral ganciclovir was most similar in efficacy to IV, although broad confidence intervals prevented a conclusive comparison. Patients receiving oral ganciclovir had a lower frequency of sepsis and IV catheter events.

CONCLUSIONS:

This study suggests that the efficacy of ganciclovir for the maintenance treatment of CMV retinitis improves with increasing total drug exposure (measured as average serum concentration AUC(0-24)). All four regimens of ganciclovir were reasonably well tolerated, with safety profiles similar to what has been reported in prior work.

• Authors: Jacob P Lalezari, Dorothy N Friedberg, Jack Bissett, Michael F Giordano, W David Hardy, W Lawrence Drew, Larry D Hubbard, William C Buhles, Mary Jean Stempien, Panos Georgiou, Donald T Jung, Charles A Robinson, Roche Cooperative Oral Ganciclovir Study Group
• Journal: Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology (J Clin Virol) Vol. 24 Issue 1-2 Pg. 67-77 (Feb 2002) ISSN: 1386-6532 [Print] Netherlands
• PMID: 11744430 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• Ganciclovir

Topics

• AIDS-Related Opportunistic Infections (complications, drug therapy)
• Acquired Immunodeficiency Syndrome (complications)
• Administration, Oral
• Adult
• Antiviral Agents (therapeutic use)
• Cytomegalovirus Retinitis (complications, drug therapy, metabolism)
• Disease Progression
• Female
• Ganciclovir (adverse effects, therapeutic use)
• Humans
• Injections, Intravenous
• Male
• Survival Analysis
• Treatment Outcome
• Visual Acuity