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Therapeutics

Foscarnet decreased the rate of progression of cytomegalovirus retinitis in patients with AIDS

ACP J Club. 1992 Mar-April;116:51. doi:10.7326/ACPJC-1992-116-2-051


Source Citation

Palestine AG, Polis MA, De Smet MD, et al. A randomized, controlled trial of foscarnet in the treatment of cytomegalovirus retinitis in patients with AIDS. Ann Intern Med. 1991 Nov 1;115:665-73.


Abstract

Objective

To evaluate the efficacy of foscarnet in slowing the progression of previously untreated cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome (AIDS).

Design

Randomized controlled trial, comparing immediate induction followed by maintenance therapy with delayed treatment with the same regimen.

Setting

Patients were referred by internists and ophthalmologists to the National Institutes of Health.

Patients

Eligibility criteria included human immunodeficiency virus (HIV) infection; cytomegalovirus retinitis (characterized by retinal infiltrates with or without hemorrhage) that was not immediately sight threatening; no previous therapy with foscarnet or ganciclovir; serum creatinine < 176.8 µmol/L; absolute neutrophil count > 500/3; platelet count > 25 × 109/L; and Karnofsky score ≥ 60.

Intervention

The 13 patients assigned to immediate treatment were hospitalized and received 60 mg/kg body weight intravenous foscarnet every 8 h over 1 h for 21 d. Patients received continuous intravenous hydration. Therapy was continued after discharge from the hospital as single daily 2-h infusions at a dose of 90 mg/kg. Control patients (n = 11) received the same treatment after they had reached a study end point. Patients were permitted zidovudine or dideoxydinosine but not systemic acyclovir therapy.

Main outcome measures

The primary study end point was progression of retinitis, defined as the movement of a retinal lesion by ≥ 750 mm across a 750-mm front into previously normal retina, or the development of a new lesion ≥ 1/16 of the disc area. Weekly stereoscopic photographs were compared in masked fashion with those from week 1. Changes in visual acuity were measured.

Main results

The mean time to progression of retinitis was 3.2 weeks (range 1 to 6 wk) for the control group compared with 13.3 weeks (range 3 to > 52 wk, P < 0.001). There was little change from a mean visual acuity of 20/25 for either group of patients. The groups did not differ in CD4+ counts. Adverse effects of therapy included nephrotoxicity (serum creatinine > 176.8 mmol/L in 23% of patients), mild bone marrow suppression, 2 instances of seizures, and a 50% rate of nausea.

Conclusion

Treatment with foscarnet reduced the rate of progression of cytomegalovirus retinitis in patients with AIDS.

Source of funding: Not stated.

Address for article reprint: Dr. H.C. Lane, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 10, Room 11B-13, Bethesda, MD 20892, USA.


Commentary

This small trial shows that foscarnet possesses some efficacy at slowing progression of early retinitis caused by cytomegalovirus in patients with AIDS. The authors speculate that foscarnet might also contribute some survival benefit because of its known anti-HIV effects. Indeed, this has been substantiated results of the much larger Studies of the Ocular Complications of AIDS (SOCA) trial comparing foscarnet and ganciclovir in patients with AIDS and newly diagnosed cytomegalovirus retinitis (1). In the SOCA trial, the drugs showed equivalent efficacy at delaying progression of retinitis, but patients with normal renal function randomized to receive foscarnet survived longer (mean survival, 12 mo vs 8 mo). The survival benefit has been attributed, in part, to the antiretroviral effect of foscarnet and to its lesser myelosuppression, which allows more patients to remain on other antiretroviral agents. This finding lends support for use of foscarnet as first-line therapy in some patients with cytomegalovirus retinitis and normal renal function.

Nowhere is quality of life a more important consideration than in a potentially blinding condition with a mean survival of 8 months. In many centers, foscarnet maintenance is delivered by pump over a 2-h period, necessitating a daily outpatient stay of several hours. For some patients, the inconvenience may outweigh the survival benefit, particularly where ganciclovir maintenance (which requires shorter infusions) is available through home antibiotic programs. Unfortunately, both these drugs have considerable toxicity. Therapeutic decision making by patients and physicians must involve not simply quantity but also quality of life considerations. Several oral agents are now under study that offer the possibility of improvements in quality of life (2). Cytomegalovirus retinitis remains an important source of morbidity for patients with AIDS and a formidable therapeutic challenge. The search for better, less toxic, and more convenient regimens is clearly imperative.

Martin T. Schechter, MD, PhD
University of British ColumbiaVancouver, British Columbia, Canada

Martin T. Schechter, MD, PhD
University of British Columbia
Vancouver, British Columbia, Canada


References

1. Mortality in patients with the acquired immunodeficiency syndrome treated with either foscarnet or ganciclovir for cytomegalovirus retinitis. Studies of Ocular Complications of AIDS Research Group, in collaboration with the AIDS Clinical Trials Group. N Engl J Med. 1992;326:213-20.

2. Spector, SA McKinley GF, Lalezari JP, et al. Oral ganciclovir for the prevention of cytomegalovirus disease in persons with AIDS. N Engl J Med. 1996;334:1491-7.