Important note: Information in this article was accurate in 1993. The state of the art may have changed since the publication date.
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TREATMENT ISSUES: The Gay Men's Health Crisis Newsletter of Experimental AIDS Therapies - Volume 7, Number 6 -- July 1993
Barclay Dunne
New Oral Formulations of both ganciclovir and foscarnet are under investigation for CMV treatment and prophylaxis. Although the oral forms of both drugs are not absorbed well, the companies remain confident that blood levels sufficient to inhibit CMV can be achieved. Oral ganciclovir is further along than foscarnet.
Introvitreal implants (Chiron Intraoptics) are small pellets surgically sewn to the inside wall of the eye which release drug directly to the site of infection. The procedure is done in twenty to thirty minutes on an out-patient basis under local anesthesia. The implants release drug directly into the eye for four or eight months. At the end of that period, the old device is removed and a new one implanted. Possible drawbacks include unknown safety risks and no drug delivered to other parts of the body where CMV may be a problem, like the colon and esophagus. Several compounds may be appropriate to use in the implants, particularly ganciclovir and HPMPC.
New CMV Prophylaxis: In addition to oral ganciclovir, valacyclovir (BW256; Burroughs-Wellcome) is in studies which examine its ability to prevent the development of CMV. BW256 is metabolized into acyclovir in the body,reaching drug levels higher than could be achieved by taking acyclovir directly. Trials are under way to determine BW256's potential as a CMV prophylaxis.
HPMPC (GS 504; Gilead Sciences) is a nucleotide analog, a new class of antiviral compounds distinct from the familiar nucleoside analogs. HPMPC has broad antiviral activity, especially against CMV. The drug is being developed in both sub-cutaneous and IV forms. Although HPMPC may ultimately be an IV drug, Gilead scientists hope HPMPC will require only once-a-week, or perhaps even once-every-other-week dosing, removing the need for a catheter. Preliminary results from Phase I safety studies indicate that the drug causes significant kidney toxicities which might be reduced with probenicid. Phase Il/III efficacy studies are in development.
Cyclobut G (BMS 180-194; Bristol-Meyers Squibb) is an oral antiviral drug nearing completion in a 40 patient Phase I bioavailability study at Johns Hopkins. Preliminary results from this study are expected within a few weeks.
Monoclonal Antibodies: MSL-109 is a monoclonal anti-CMV antibody. Although monoclonal antibodies were originally dismissed for AIDS-related uses, a phase I study presented at the Berlin AIDS Conference suggested that MSL-109, when combined with either ganciclovir or foscarnet, may delay progression to CMV disease.
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