LETTER
Cidofovir for Cytomegalovirus Retinitis
Stephen Kravcik, MD, FRCPC
15 September 1997 | Volume 127 Issue 6 | Page 490
TO THE EDITOR:
The demonstration of the effectiveness of cidofovir to treat cytomegalovirus (CMV) retinitis adds a welcome third drug to the list of anti-CMV therapies. However, it is most disturbing to find that the two clinical studies of this compound [1, 2] compared it with no treatment ("deferred therapy").
There is no doubt that the natural history of untreated CMV retinitis is one of relentless progression and that ganciclovir [3] and foscarnet [4] are both effective. Therefore, the withholding of proven therapy (even with close follow-up) in the context of a clinical trial to demonstrate the effectiveness of cidofovir is unacceptable. The rationalization that only patients with peripheral retinitis were enrolled is irrelevant and of questionable prudence because 4 of 23 patients in the no-treatment group developed sight-threatening retinitis and another patient developed extraocular CMV infection.
The provision of informed consent by the participants of these studies does not render the withholding of proven therapies for the purposes of demonstrating cidofovir's effectiveness any less unethical. I must admit that I was surprised that these studies were approved by the study institutions' ethics review boards. Similarly, regulatory requirements and the fact that previous studies of anti-CMV therapies have been compared with placebo provide no justification for the nontreatment of an opportunistic infection in an experimental protocol. We would not consider withholding therapy for Pneumocystis carinii pneumonia or cryptococcal meningitis to prove that a new compound is efficacious.
Surely, there must have been enough suspicion of the potential effectiveness of cidofovir to allow for a direct comparison with ganciclovir or foscarnet. This would have been far more ethically acceptable and would have gone far to delineate the potential role of cidofovir in the treatment of CMV retinitis.
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Author and Article Information
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Ottawa General Hospital; Ottawa, Ontario K1H 8L6, Canada
1. Lalezari JP, Stagg RJ, Kuppermann BD, Holland GN, Kramer F, Ives DV, et al. Intravenous cidofovir for peripheral cytomegalovirus retinitis in patients with AIDS. A randomized, controlled trial. Ann Intern Med. 1997; 126:257-63.
2. Studies of Ocular Complications of AIDS Research Group in Collaboration with the AIDS Clinical Trial Group. Parenteral cidofovir for cytomegalovirus retinitis in patients with AIDS: the HPMPC Peripheral Cytomegalovirus Retinitis Trial. A randomized, controlled trial. Ann Intern Med. 1997; 126:264-74.
3. Collaborative DHPG Study Group. Treatment of serious cytomegalovirus infections with 9-(1,3-dihydroxy-2-propoxymethyl) guanine in patients with AIDS and other immunodeficiencies. N Engl J Med. 1986; 314:801-5.
4. Studies of Ocular Complications of AIDS Research Group, in collaboration with the AIDS Clinical Trial Group. Mortality in patients with the acquired immunodeficiency syndrome treated with either ganciclovir or foscarnet for cytomegalovirus retinitis. N Engl J Med. 1992; 326:213-20.[Abstract]
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