TreatmentUpdate60; Volume 7, No. 6 - June 1995
Sean Hosein

All 16 subjects in this study were adults (15 males, 1 female) with AIDS, and had 'active' CMV infection in the eye despite treatment with intravenous ganciclovir and/or foscarnet. Some potential subjects with complications including eye inflammation, infection of the eye with other microbes or detached retinae were not allowed to enter the study. There were 2 stages in this study. In the first part doctors enrolled 9 subjects and used them to look for toxic effects from the eye injections while giving them intravenous ganciclovir. In the 2nd part of the study, doctors were trying to find out about the anti-CMV effects of cidofovir.

As with the studies of intravenous HPMPC, most subjects in this trial received 2 g of probenecid 3 hours before having their eye injections and later, "1 g orally each at 2 and 8 hours after cidofovir injections." To inject the drug doctors used a "30 gauge needle attached to a tuberculin syringe."

* RESULTS-PART 1

In the first part of the study, 9 subjects received various doses of cidofovir ranging from 10 to 100 microgrammes. Half of these subjects were monitored for about 76 days and doctors examined their eyes weekly. Three subjects had complications-"[inflamed eyes, changes of the pressure inside the eyeball]". By the end of the study, over 90% of untreated eyes had worsening damage from CMV despite continued intravenous ganciclovir.

* RESULTS-PART 2

For this experiment doctors injected cidofovir into 8 eyes. About half of subjects receiving an injection of cidofovir 20 pg (microgrammes) had worsening eye damage from CMV 64 days later. No serious complications as a result of the injections occurred.

* RECOMMENDED DOSE AND WARNINGS

The researchers stated that in "every [subject] treated with cidofovir alone", eye damage by CMV was blocked. They "recommend and use a dose of 20 pg cidofovir" when treating their patients with CMV retinitis. They are not sure that probenecid provided any protection against eye damage caused by cidofovir. As well, while complications from eye injections were few, the researchers warn that:

"[complications from eye injections] may not be entirely preventable despite [very careful and skillfill] technique, [the risk of this happening] must be [carefully explained] to any patient [thinking about eye injection] therapy for CMV retinitis."

* PROBLEMS GETTING HPMPC

Although originally found in plants, chemists can now make HPMPC in their labs. In the USA the company Gilead Sciences (Foster City, California) is developing cidofovir as an intravenous therapy for CMV. The HPMPC used in this study was made by researchers in Belgium because Gilead refused to supply it for the experiments with eye injections. An investigation by Jon Cohen for the journal Science suggests that Gilead refused to supply the drug because "...it wouldn't make much profit from the small, infrequent doses used in the [eye injections]." One American treatment activist said that "[a]ny effort to move forward on intravitreal treatment has been completely stonewalled by the company." A senior staff person at Gilead denies that this is the case. Gilead hopes that the FDA will approve the use of IV cidofovir for the treatment of CMV infection. The company also plans to conduct a study of injecting HPMPC into the eyes of subjects to confirm the data from this independent study.

ACKNOWLEDGEMENTS:

1. We thank B. Goldberg for rapid access to this research.

REFERENCES:

1. Kisch LS, Arevalo JF, De Clercq E, et al. Phase I/II study of intraviteal cidofovir for the treatment of cytomegalovirus retinitis in patients with the Acquired Immunodeficiency Syndrome. American Journal of Ophthalmology 1995;119(4):466-476.

2. Cohen J. AIDS drug: experiencing local delays. Science 1995;268:369.

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Copyright © 1995 - TreatmentUpdate. Reproduced with permission. Reproduction of this article (other than one copy for personal reference) must be cleared through the Editor, The Canadian AIDS Treatment Information Exchange, 555 Richmond St. West, Suite 505, Box 1104, Toronto, ON, M5V 3B1 • Phone: 416-203-7122 • Toll Free: 1-800-263-1638 • Fax: 416-203-8284  http://www.catie.ca