THE DIFFICULTY IN PERFECTING ANTIVIRAL DRUGS
It would be nice to entitle this chapter “How to Cure Herpes.” Perhaps some future book on herpes will have such a chapter. For now we must be content to treat the disease as best we can, given the medical knowledge of the 19805. Big strides are now being made. In fact, if this book had been written less than a year earlier, there would have been no treatment at all to share with you.
Viruses, unlike bacteria, enter a latent period in the human host. During this period of dormancy they maintain what might be referred to as an equilibrium with the host. As long as the person is healthy and the immune system strong the virus maintains a status quo. No damage is done. It remains quietly in the sacral or trigeminal ganglia. Should the host become run down or the immune system be compromised for any of the reasons we have discussed in this article the virus is quite capable of traveling down the nerve pathways to cause pain and do its damage.
The virus does its damage by taking control of the human cell and instructing it to make other viruses. In the process the cell is destroyed. Bacteria, on the other hand, enter the body and do their damage outside the human cell. They do not need to commandeer a cell in order to wreak havoc. As a consequence, treating bacteria somewhat less difficult and not as dangerous. If an undesirable organism can be attacked with drugs while it is outside the cell there is less chance of doing damage to the delicate cell. Virus, on the other hand, is difficult to attack pharmacologically, because a drug must enter the cell before it can reach the virus. Once the drug reaches the inside of the cell and gets to the virus there is the danger that it may act on the cell. Ideally a drug will attack the virus without harming any portion of the cell and without changing the chemical balance of the cell.
The solution for the problem is even more complicated when you consider the other criteria. The antiviral drug must be able to pick out the cells containing the virus and leave normal cells alone. The drug must also be potent enough to destroy the entire virus particle without leaving any fragments that may cause problems later on. This is not easy to do. One inherent danger in sending a drug to alter the inside of a cell is the danger of altering the chemical makeup of the cell itself. As we learned in Chapter Seven, an altered or abnormal cell has the potential to become cancerous. Consequently, any antiviral drug must be a technical marvel capable of carrying out tasks beneficial to the cell at the same time it leaves the surrounding area free of undesirable change. In other words, the viral cycle must be broken without damaging normal cells.
Antiviral compounds are a new addition to the world of science. Not until the 1970s was a compound developed that proved effective. One of the first available was an antiviral drug used in treating herpes keratitis, Idoxuridine (IDU). It was found to be effective in preventing blindness in cases of herpes keratitis. It was tried on other types of herpes, including topical application to herpes lesions, but without success. When tried systemically in the treatment of herpes encephalitis, IDU interfered with the replicative cycle of normal cells. It was therefore judged unsafe for internal use.
Despite their limitations, antiviral drugs are being actively researched and in the years to come treatments that seem impossible today will be available. Antiviral drug scientists are attacking viruses on several fronts, mostly trying to disrupt the viral manufacture of genes that can endanger healthy cells. Even as successful compounds are developed, they will be more a treatment than a cure. When a person takes an antibiotic to kill bacteria, all bacteria sensitive to that antibiotic are destroyed, assuming the proper dosage was administered. An antiviral drug works on the virus only during periods of active infection, while the virus is undergoing replication. Until an antiviral drug can attack viruses in their latent state, a cure is unlikely.
While a cure may not be just around the corner, antiviral drugs are useful in decreasing the production of viruses. This is important because the less the production, the less severe the infection. Also, a recurrence is less likely with a lower number of viruses available in the body from which to draw.
In spite of research and progress directed toward antiviral drugs, a recent statement in the British Medical Journal (July 16, 1983) supports that “for established recurrent herpes, a simple saline bath and talcum powder are as effective and much cheaper than any available antiviral drugs, particularly since recurrent attacks are much milder and of shorter duration and heal more quickly, and in most cases the intervals between attacks are longer.”‘ This is mentioned’ more to add another mode of treatment to aid in comfort during recurrence rather than to discount the effectiveness of acyclovir.
INTERFERON—THE NATURAL APPROACH
In 1957 Drs. Alick Isaacs and Jean Linden discovered that the body manufactures its own antiviral drug, interferon. You may have read much about this substance and the medical community has great hopes for it. Interferon not only appears to work against all viruses but it seems to have low toxicity. Interferon can inhibit the replication of numerous viruses without affecting normal cell structure. You probably know from extensive media coverage that interferon is enormously expensive. In fact, due to its expense, it cannot be made widely available at this time. This problem led researchers to try to “trick” the body into manufacturing more interferon than it normally would. First attempts at this resulted in undesirable side effects, but research continues in this all- important field. The potential of this substance is as great as the hope we all have for its success.
ACYCLOVIR—TREATMENT AVAILABLE NOW
Acyclovir was discovered in 1974 by Howard Schaeffer and Lilia Beauchamp of the Burroughs Welcome Company. Studies showed that acyclovir killed herpes viruses without damaging healthy cells. Acyclovir interferes with the herpes virus’s DNA synthesis, prohibiting the virus from replicating to the extent it normally would. Approval by the FDA of this drug was based not only on experiments in test tubes but on animal research for several years. Clinical trials in the late 1970s and early 1980s proved effective against genital herpes. Most clinical tests were conducted at the University of Seattle, Emory University in Atlanta and the University of Vermont. The clinical trials demonstrated that acyclovir speeded the healing of initial genital herpes infections, reduced viral shedding (the length of time that live herpes viruses are present in sores and able to be transferred from person to person through sexual contact) and sometimes reduced pain from initial infections. Another trial tested acyclovir’s effectiveness against localized HSV-1 and HSV-2 infections on the surface of the bodies of immunosuppressed patients. Extensive testing is still taking place and it is hoped that acyclovir will prove to have benefits heretofore undiscovered.
Clinical investigation centered around acyclovir has shown oral administration to be an effective modality of treatment in HSV infections. Studies have been carried out where patients were allowed to begin oral therapy (200 mg, five times daily) upon the recognition of prodromal signs of an infection. According to Dr. Richard C. Reichman, et al., with this self-initiated therapy, results provided “definitive evidence that administration of an antiviral drug can shorten the duration of recurrent nucocutaneous HSV infections.” However, additional approaches are required to prevent recurrences of genital HSV infections. Evidence substantiates the ability of prophylactic therapy to suppress recurrences while the drug is being taken, but when the treatment is stopped the disease relapses?