MEDICAL UPDATE: What's Behind the Headlines About Acyclovir?

MEDICAL UPDATE: What's Behind the Headlines About Acyclovir?

Being Alive; February 1992
Mark Katz, MD, reported by Warren Jones and Walt Senterfitt

Over the holidays, London newspapers headlined: "AIDS Deaths Cut in Half by New Drug." It would be wonderful if this were true, but it's not. The study referred to acyclovir, which of course is not a new drug. The news stories reported the premature termination of a study in the United Kingdom, Germany and Australia. Several hundred people with T-cell counts over 150 were randomized to receive either AZT plus a placebo or AZT plus high-dose acyclovir (3200 milligrams a day). The study was intended to see if high-dose acyclovir can prevent CMV retinitis. While the study had not shown any difference in the incidence of retinitis, it did show an apparent survival advantage for the combination over AZT alone. After one year, there had been 30 deaths out of 150 patients in the AZT-only group compared to only 15 deaths out of 150 taking AZT plus acyclovir. Therefore, analogously to the AZT vs. DDC study, it was considered ethically untenable to continue and everyone was offered the combination.

This development is more difficult to interpret, however, at least on the basis of sensational news reports rather than an article or detailed summary of the findings. For instance, what did cause the deaths in the study? Were there, for example, fewer CMV-related deaths?

There have been previous studies of combination therapy with acyclovir and AZT, with conflicting results. Dr. David Cooper of Sydney, Australia, has reported significantly better outcomes in several of his combination therapies. Several studies in this country have failed to replicate these results.

Acyclovir is used as a rather effective and relatively non-toxic drug against herpes virus infection. Since other infections may well be cofactors promoting more rapid progression of HIV disease, anyone with a history of herpes simplex infection would quite likely benefit from its suppression with acyclovir. Some think it may also have action against CMV, which is a member of the family of herpes viruses. Suppressing CMV would, of course, be a good thing, in itself and to remove another possible cofactor with HIV. The problem is that most laboratory and clinical evidence shows that acyclovir is NOT particularly effective against CMV.

Though this interrupted study does not answer these questions, it does bring the role of acyclovir into the spotlight again. One reasonable conclusion is that if the drug does have a CMV-suppressing or life-extending effect, it is probably in higher doses (3200 mg a day as in this study) than usually given.
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