CMV UPDATE

AIDS TREATMENT NEWS #94 carried of brief report on the latest developments in the treatment of herpes and CMV infections. Recently we spoke with knowledgeable people who had additional information.

Our article had suggested that ganciclovir, approved last year by the FDA, may be at least as good a treatment as Foscarnet, which remains experimental. But some people cannot use ganciclovir because of its toxicity -- especially those who are also using AZT, which has similar toxicities -- and therefore they should have access to Foscarnet.

Dale Henderly, M. D., who practices ophthalmology at Northwestern University and has treated many people with CMV retinitis, suggested some other approaches for these patients. He pointed out that the new anti-HIV drug ddI can be administered simultaneously with ganciclovir in many patients, since the drugs have different toxicities. He also feels that if neutrophil counts are within normal limits during treatment with ganciclovir, the patients may be able to tolerate the newly lowered dose of AZT, 500 mg a day.

If ganciclovir cannot be used with either ddI or AZT, then theoretically no obstacles would prevent access to Foscarnet, through a clinical trial or compassionate use. But Dr. Henderly urged people newly diagnosed with CMV to seek the care of a physician experienced with AIDS treatment, so that all the options for dealing with both HIV and the opportunistic infection will be explored. One example is the possibility of entering a clinical trial of granulocyte macrophage-colony stimulating factor (GM- CSF), an agent which looks promising as a control for bone-marrow suppression induced by AZT or ganciclovir.

An experimental use of ganciclovir which may avoid the systemic toxicities involves intraocular administration of the drug. This method uses a small needle to inject the ganciclovir directly into the eye, which delivers the treatment to the
specific site of the infection. Although this mode appears to be successful for stabilizing the retinitis, it is not especially practical or safe, as the injections must be repeated twice a week indefinitely, and they risk introducing other eye infections. However, intraocular injections remain a potential "salvage" option if other attempts to treat CMV fail.

Dr. Henderly also told us that laser therapy should not be construed as a treatment for retinitis. Rather, lasers have been used to correct a complication of treating retinitis -- the detachment of a retina which has become thin and fragile because of prolonged treatment. Even in this context, lasers have been only moderately useful, and only for detachments which were not severe. Dr. Henderly added that lasers have also been tried as attempts at "sealing off" the retina to prevent detachment, but results were unconvincing.

For retinal detachments which are too severe to correct with laser surgery, Dr. Henderly suggests the use of silicone oil to replace the vitreous interior of the eye; this treatment usually works to hold the retina in place again. The silicone oil, like laser treatment, has no therapeutic effect on the CMV infection.

Future Possibilities

The antiviral HPMPC is looking especially promising in animal studies for treating CMV and perhaps other herpesvirus infections. But as far as we know, it has never yet been tried in humans; therefore it is too early to know whether it will ever be a useful drug. An early report on animal studies was published as an abstract at the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), September 17-20, 1989, abstract number 751; for other background see AIDS TREATMENT NEWS #76, March 24, 1989.

Other potentially important CMV treatments are FIAC and oral ganciclovir, both now in small-scale clinical trials. For more information on FIAC, see AIDS TREATMENT NEWS # 94. We do not know how well this drug is working. For more information on oral ganciclovir trials, see "San Francisco, San Diego: Oral Ganciclovir Study Seeks Volunteers," below in this issue; also see AIDS TREATMENT NEWS #89. Oral ganciclovir has the same toxicity as the approved intravenous treatment; its advantage is avoiding the need for intravenous infusion.

AIDS TREATMENT NEWS believes that the most important action to improve treatment for CMV and other herpesviruses would be to speed the development of HPMPC. Apparently this potential drug works very well in the well-established "animal model" for CMV infection; if it passes standard toxicity tests, there would be no shortage of volunteers willing to try it as a therapy. When a new drug is potentially so important to so many people, its development should be treated as an emergency, not business as usual.