AIDS TREATMENT NEWS Issue #189, December 17, 1993 phone 800/TREAT-1-2, or 415/255-0588 CONTENTS: HIV and Psychiatric Treatments: Interview with J. Kevin Rist, M.D. IL-12: Potential Treatment Restores Immune Response in Laboratory Test Advanced AIDS: Alert for CMV Polyradiculopathy. Interview with Lawrence Drew, M.D., Ph.D. Voicemail Announcement System for Coordination at Conferences, Elsewhere AIDS TREATMENT NEWS Selected Index, Through 1993 ***** HIV and Psychiatric Treatments: Interview with J. Kevin Rist, M.D. by Denny Smith The debilitations of HIV are not always physical. Many people with HIV infection experience mental and emotional troubles that may contribute to the decline of their physical health, and yet be missed by physicians who are trained to focus on tangible illness. Like physical disease, however, psychiatric symptoms are often treatable. People who face ongoing depression or anxiety often find therapy or counseling valuable, and many community-based agencies can offer such therapy to people with HIV. Sometimes, however, a counselor or social worker will suggest a consultation with an HIV-experienced psychiatrist, who can offer pharmacological treatment when helpful. We interviewed J. Kevin Rist, M.D., to gain some insight into the psychiatric facets of HIV disease. Dr. Rist is an attending psychiatrist in the HIV Services department at St. Mary's Hospital and Medical Center in San Francisco. He also cares for a number of HIV-infected clients in his private practice. * * * DS: Is your treatment approach to HIV-infected patients significantly different from your treatment for other patients? KR: It's not very different from treating other patients who are also dealing concurrently with physical illness. For example, physical illness often means that these individuals are in fragile health and are already on a number of nonpsychiatric drugs. So you have to be aware of drug side effects, and interactions. Most of all, people come to us hurting or suffering, or needing something. It's not always comfortable for human beings to need something from, or to be dependent on, someone else. It's a vulnerable situation. I think it's particularly common for patients facing a life- threatening illness to get depressed, to feel anxious, to have sleep disturbances. DS: What would you say to primary care physicians who are not accustomed to assessing or treating psychiatric symptoms in their patients? KR: Physicians in other specialties are often very preoccupied, quite legitimately, with other things. But I think it's generally true that depression and anxiety are underdiagnosed in people with HIV, and if an internist can gain familiarity with treating psychiatric symptoms in their patients, that's good. Unfortunately, what I see a lot of, in patients referred to me by primary care providers, is the misprescription of benzodiazepine drugs: lorazepam (Ativan), diazepam (Valium), alprazolam (Xanax), flurazepam (Dalmane), temazepam (Restoril), triazolam (Halcion). I think that people perceive those drugs to be safe, but actually they are very addictive. You quickly build up a tolerance for them, and need more to obtain a therapeutic effect. Then both the patient and the doctor may find themselves in a quiet struggle over the issue, with the patient feeling guilty for wanting more and the physician feeling guilty for prescribing more, and the whole issue unnecessarily becoming an interpersonal one. If, instead, the physician were a little more savvy, and noticed some anxiety symptoms or trouble sleeping at night, he or she might ask more questions and realize these are really manifestations of depression, and treat them with the proper antidepressant medication, or refer them to someone who will treat accordingly. That way the patient will get better symptomatic relief, be more motivated to trust the doctor and work with the doctor, and avoid getting into a self-destructive cycle of being dependent on something that only their doctor can give them. DS: So the benzodiazepines are not antidepressants? KR: No, they are approved and marketed for various other indications, such as immediate anxiety. They are not appropriate for long-term therapy. Using them to treat depression is a little like treating a serious fever with aspirin, without delving further into the underlying cause of the fever. If someone is extremely troubled, I may offer a benzodiazepine like lorazepam along with an antidepressant like imipramine, and taper off the lorazepam as the antidepressant takes effect, which can take several weeks. I've seen patients who were actually on two different benzodiazepines-one for anxiety and one for sleeplessness. That kind of combination can cause cognitive impairment and even be dangerous, especially when mixed with alcohol. So rather than treating every symptom with a different medicine, I like to see people on simplified, clean regimens of psychiatric medications. DS: On a related note, a lot of people with HIV have a history of recreational drug use, and a lot of people with a history of chemical dependency are now HIV-infected. And yet we are perhaps finally emerging from the Reagan/Bush approach to drugs, now considered essentially a nonproductive social policy. What is a productive attitude in the 90s? KR: I want patients to feel safe to talk about drug use. If someone is now using drugs, I talk to them about what they want to do with their life. You can be clear that you don't approve of something that's not in their best interest, and still maintain a mutually respected position with each other. You can express disapproval of a behavior rather than a person. With a punitive or a "just say no" approach, you're just going to lose the patient; you have no chance of helping someone who leaves your care. So the first question I ask on this issue is "Are drugs or alcohol a problem for you--have they ever caused you any negative consequences?" If the answer is "No," and I don't perceive any problems, like elevated liver enzymes, then the issue is set aside. If the answer is "Yes," or "Sometimes," then I ask "Why do you continue using them--would you like me to help you with this?" It is not productive to be judgmental. If you want someone to be capable directing their own life, then on some level you have to be comfortable with them directing their own care. DS: Which psychiatric drugs are appropriate in the context of HIV care? KR: Except for the benzodiazepines, I'll rely on the traditional antidepressants, such as the tricyclics-- amitriptyline (Elavil), imipramine (Tofranil), nortriptyline (Pamelor)--as well as the newer generation, such as fluoxetine (Prozac) and sertraline (Zoloft). Although these are specifically indicated for treating depression, by extension they can also relieve anxiety and problems sleeping. I think that low-dose antipsychotics, such as perphenazine (Trilofon), are good for treating overwhelming anxiety, or psychotic depression, especially in patients who have not responded to the other drugs. DS: How do you distinguish depression and anxiety from the early symptoms of dementia? [For a larger discussion of cognitive and motor deficits, see AIDS TREATMENT NEWS issue number 171, March 19,1993.] KR: It's important to remember that most cognitive impairment is not dementia. First, of course, you are obligated to look for any life-threatening opportunistic diseases, using whatever neurologic tests are appropriate--MRI [magnetic resonance imaging] or LP [lumbar puncture], etc. Then you ask if drugs are a factor, either prescribed or recreational drugs. Then you try to rule out psychiatric symptoms, such as depression. HIV-associated dementia is the remaining diagnosis to make in the situation. DS: For a number of years, the dominant mental health model of "how to be" a person with AIDS was basically a death and dying model. It was not a monolithic model, but the aggressive treatment approach largely took a back seat to the acceptance of death. There are still health care providers who routinely refer to HIV infection as a terminal illness, rather than a life-threatening disease. How is it possible to view HIV as something to survive, or at least to live with? KR: Having HIV now should be seen as dealing with a chronic illness. I have at least two patients who are long-term survivors. Neither of them ever expected to remain healthy or even to be around this long, and they have had to find the strength to survive the losses all around them. One of them was once told that he had only six months left to live. That was ten years ago, and people like him now present the psychiatric community with a whole new set of issues, including how to live when you didn't expect to, how not to die. ***** IL-12: Potential Treatment Restores Immune Response in Laboratory Test by John S. James IL-12, a newly-discovered substance which is naturally present in the body in small amounts, has been found to restore certain immune responses which are diminished or lost in HIV infection.(1) This result, recently published by researchers at the U.S. National Cancer Institute, was found in cells of HIV-positive donors. IL-12 was administered to these cells in a laboratory test. IL-12 has not yet been tested in humans, but clinical trials are expected in 1994. [Note: Do not confuse IL-12 with IL-2, another immune modulator which is also being tested as a potential AIDS treatment.] Two of the researchers on this study, Mario Clerici, M.D., and Gene M. Shearer, Ph.D., proposed a theory earlier this year of a "TH1-to-TH2 switch" -- a change in immune function which occurs in HIV infection, and may cause the disease to progress faster.(2) According to this theory -- which is accepted by many but not all researchers -- in early HIV infection, the body first defends itself effectively against the virus by one kind of response (called the TH1 response; 'TH' stands for T-helper); this response consists mainly of cellular immunity, i.e. certain cells which destroy infected cells. But then, while the patient is still asymptomatic, the immune system switches to a TH2 response, which mainly produces antibodies, which appear to be less effective than cellular immunity in controlling HIV infection. Each kind of response tends to suppress the other; so when the switch to a TH2 response occurs, the protective TH1 response is largely lost. IL-12 may reverse this switch and restore cellular immunity against HIV and other pathogens. Two teams, Genetics Institute, Inc., Cambridge, Massachusetts, working with the Wistar Institute, Philadelphia, Pennsylvania, and Hoffmann-La Roche, Inc., Nutley, New Jersey, each independently discovered IL-12. Genetics Institute and Wistar initially named their discovery Natural Killer-cell Stimulatory Factor (NKSF). Roche named its discovery Cytotoxic Lymphocyte Maturation Factor (CLMF). Genetics Institute and Roche have agreed to cross-license each other so that each company may proceed independently in the further development of IL-12. A December 10 news release from the National Cancer Institute explained the new IL-12 study. It is the best description for non-scientists, so we reproduce it in full: "National Cancer Institute (NCI) scientists have succeeded in restoring normal immune responses to cultured cells from HIV- infected donors. The scientists used a natural blood substance, interleukin-12 (IL-12), which will be tested in asymptomatic HIV-positive individuals within the next several months. HIV is the virus responsible for AIDS. "T lymphocytes from many HIV-infected people do not show normal immune reactions when they are exposed to antigens such as influenza virus. By adding the immune regulator IL-12 to cultures of these cells, the NCI scientists and their colleagues