Imuthiol Plus Acyclovir: One Physician's Experience

We spoke with Michael Lange, M. D., of St. Luke's-Roosevelt Hospital Center at Columbia University, who has 15 patients who have used Imuthiol, plus six acyclovir tablets per day, for at least two years; most did not use AZT. These 15 started with T- helper counts between 100 and 275. While the number of patients is small and the results are based on clinical experience and not a controlled trial, Dr. Lange believes that the outcome with these patients is clearly better than would have been expected with other treatments, and that it is important for this information to be known.

Dr. Lange's experience with Imuthiol began in 1987, when one of his patients went to France and enrolled in a trial there. Because the protocol called for blood tests every two months and the patient did not want to return to France every time, Dr. Lange agreed to perform the tests according to the study protocol; he also added other blood work, including acid- labile alpha interferon, a research test which indicates poor prognosis when the substance is found in the blood. Subsequently, other patients enrolled in the French study and made the same arrangements to be tested in New York.

Dr. Lange does not favor AZT, and the patients who come to him are usually self-selected for not wanting to use it. He does use AZT in two situations, however. If the patient is already taking AZT, Dr. Lange continues it because of the possibility of a rebound effect if antivirals are stopped. Also, if acid-labile interferon is found in the blood, Dr. Lange prescribes AZT because his experience has shown that Imuthiol plus acyclovir by itself is not enough -- and because the acid-labile interferon tends to disappear after AZT treatment.

Most of the 15 patients are using few other treatments except for pneumocystis prophylaxis -- preferably Bactrim, or aerosol pentamidine for those who cannot tolerate Bactrim.

Results

At the June 1991 Seventh International Conference on AIDS in Florence, Dr. Lange presented a poster on predictors (other than T-helper count) of prolonged survival (abstract #W. A. 1224) The published abstract, based on experience with 20 patients, does not mention Imuthiol; its main conclusion is that the presence of acid-labile alpha interferon was correlated with unfavorable prognosis, with death after an average of about 30 months, whereas those with the same T- helper counts who did not have interferon remained essentially asymptomatic during the average of 33 months that they had been followed.

After the abstract had been submitted in January, Dr. Lange noticed that eight of the ten patients who remained largely asymptomatic for 18 months were using Imuthiol -- while none of the ten patients who died had used the drug, or at most they had used it for no more than two to three months. This observation was only suggestive, because the patients included were selected subjectively, but it led Dr. Lange to look more closely at those who had been taking Imuthiol for an extended time.

The experience with all his Imuthiol patients suggested that those who had not developed acid-labile alpha interferon in the blood when they started treatment with Imuthiol plus acyclovir -- and who did not have this blood marker at the time the second test was run (two months after start of treatment) -- seemed to remain stable, essentially asymptomatic and without major decline in T-helper counts, for the two years or more that they have been observed. All 15 who met these criteria did remain stable. Also, none of them developed high levels of p24 antigen; in the few who had any detectable amount, it was below 50. This small cohort of patients, who started with T-helper counts of 100-275, would not have been expected to have done nearly as well without the Imuthiol and acyclovir.

Dr. Lange emphasizes that it takes a long time to see the benefits of Imuthiol, because when it is started at T-helper counts of about 150, the hope is for stabilization rather than dramatic improvement. For this reason he was reluctant to speak publicly about his results until he had two years of data. And because a double-blind study was running in France, he decided to wait for its results, hoping they would confirm his observations. The disappointing preliminary results from that trial -- which first became known last week -- has left the status of Imuthiol confused; no one knows why they are different from Dr. Lange's observations, and different from previous controlled trials of the drug, which showed benefit. Dr. Lange has not seen the protocol of the European trial, and at this time he is unwilling to advise his patients to stop using Imuthiol. He also emphasizes that his regimen included the acyclovir, so it is not directly comparable with the trial, which used Imuthiol alone.

Why Add Acyclovir?

Dr. Lange added acyclovir to the regimen because of a series of discoveries by clinicians, many of them accidental.

First, physicians performing bone-marrow transplants (not AIDS related) had tried high-dose acyclovir as prophylaxis against herpes simplex infections, which can be fatal in these patients. The physicians not only found less herpes, but also, quite unexpectedly, less CMV pneumonitis, a major cause of death in these patients. At least two studies have been published showing successful CMV prophylaxis with acyclovir in non-HIV immunosuppressed patients.

Then Craig Metroka, M. D., of St. Luke's-Roosevelt Hospital, tried high-dose acyclovir (4 tablets five times a day) for prevention of CMV, in patients with a median T-helper count of 64. Only two of the 120 who received the treatment developed invasive CMV, whereas five of the 14 who refused treatment did. None of the treated patients developed herpes simplex or herpes zoster, and hairy leukoplakia cleared in all 16 who presented with it. Of five whose doses were reduced by half, three developed invasive CMV. This result was published with the abstracts of the Sixth International Conference on AIDS, San Francisco, June 1990 (abstract #2111).

Dr. Lange heard of Dr. Metroka's work long before publication and started his patients on acyclovir in May 1989. His patients were at less risk of CMV, however, and he was reluctant to put them on so high a high dose indefinitely, so he selected a smaller dose.

Other information which contributed to the rationale for using acyclovir included laboratory findings suggesting that herpetic viruses might stimulate growth of HIV.