&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& J O H N J A M E S writes on A I D S &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& Copyright 1993 by John S. James; permission granted for non-commercial use. AIDS TREATMENT NEWS Issue #171, March 19, 1993 phone 800/TREAT-1-2, or 415/255-0588 CONTENTS: [items are separated by "*****" for this display] Understanding Dementia and Neurologic Disorders: Interview with Elyse Singer, M. D. Eyesight, Hearing, Speech: Potential for Rehabilitation Often Ignored When Treating AIDS Notes: Alpha-APA Derivative R89493: Technical Article Published Searchlight, March/April 1993 ***** Understanding Dementia and Neurologic Disorders: Interview, Elyse Singer, M. D. by Denny Smith Of all the physical and emotional difficulties which HIV disease can present, those involving the nervous system may be the most troubling and least understood. Many neurologic problems are broadly associated with opportunistic illnesses, or with the side effects of certain drugs. However, HIV itself can have a number of effects on the nervous system, ranging from subtle disorders to serious ones. It is important to know that many of these respond to treatment. Direct HIV involvement can impair cognitive (thinking) or motor (coordinated movement) abilities, but it should be distinguished from neurologic symptoms of infections and malignancies that can appear in the wake of immune suppression, such as toxoplasmosis, CMV or herpes encephalitis, cryptococcal meningitis, progressive multifocal leukoencephalopathy (PML), neurosyphilis and lymphoma. A fairly reliable diagnosis and treatment "pathway" has been established for most of these. Other problems of the nervous system can be "iatrogenic" in nature, meaning they are the unintentional and sometimes unavoidable effects of medical treatment. Examples are the peripheral neuropathy that can result from the use of ddI, ddC or vincristine, or myopathy (muscle damage) that can follow the long-term use of AZT, or delirium sometimes associated with ddI or ganciclovir. Some neurologic symptoms are easy to confuse with depression and sleep disorders, which can be a natural response to the stresses of living with HIV. But chronic, immobilizing depression or sleeplessness warrant treatment with appropriate therapy or drugs. Since opportunistic illnesses, drug toxicities, or depression are often either urgent or easy to treat, they are likely to be considered first when someone goes to their doctor with a neurologic symptom. In contrast, cognitive or motor disorders caused directly by HIV may be the least urgent, clinically speaking, and the last treated of nervous system diseases. HIV may colonize the brain, nerves, and muscles early in the infection, but this process is clinically "silent" in most people until they are immune suppressed. Fortunately, the virus does not directly infect neurons, which are the circuits of consciousness and memory. Nevertheless, for reasons explored below, even non-neuronal HIV neurologic activity can lead to serious deficits in cognitive and motor functions in some people. At one time, all neurologic deficits caused directly by HIV were ominously described as "AIDS dementia complex." That has given way to the more accurate, if more clumsy, "HIV-associated cognitive and motor complex." Dementia can be part of this complex, but it is only a late development in a spectrum of cognitive or motor deficits. Limited research so far suggests that these deficits can respond to treatment. In other words, HIV can impair the way people think and move, but that impairment may be reversible given the preservation of neurons and intervention with effective therapies. We asked HIV neurologist Elyse Singer, MD, to share her experience and expertise with HIV neurologic disease. Dr. Singer is an Assistant Professor of Neurology at the University of California Los Angeles Medical School, and a research physician at West Los Angeles Veterans Administration Medical Center. [Editor's note: This article, published for both patients and medical professionals, includes some medical terminology which would usually be avoided or explained in AIDS TREATMENT NEWS. In some cases, especially when words are used only as examples and are not necessary for understanding the main points of the article, we felt that a definition or explanation would be an unnecessary distraction. Readers should realize that they do not need to know every word in order to understand this interview.] * * * DS: How extensive are nervous system problems in HIV disease, and what is their relationship to HIV dementia? ES: The new classification, of course, for these is HIV- associated cognitive and motor complex. This includes what we once called AIDS dementia, AIDS encephalopathy (brain disorder), and AIDS myelopathy (spinal cord disorder). In the past, there was a tendency to lump together all HIV-associated involvement of the central nervous system as dementia. But in fact, many of these people did not meet the criteria for dementia that would be applied to other diseases, such as Alzheimer's. Dementia is a persistent, disabling loss of cognitive function, and may be caused by damage to the brain from a number of diseases. Some people with HIV neurologic impairment have mostly motor symptoms, and some patients have minor, rather than major, cognitive problems. So it is inappropriate to call them demented. Minor involvement means that someone is slightly below their baseline in terms of their ability to think or use their motor skills. Dementia would involve a persistent cognitive deficit that disables a person from doing their work or activities of daily living. If people are so disabled, they may be given a diagnosis of dementia. In perhaps one-third to two-thirds of people with dementia, there is an associated problem with the spinal cord called vacuolar myelopathy. The symptoms of this are difficulty walking and trouble with bowel and bladder control. Infrequently, you might see this myelopathy without dementia. Dementia is a term that has very important medical and legal implications, and it carries a lot of social stigma for people. It should not be applied indiscriminately. DS: For those reasons and others, a lot of people are very afraid of developing dementia. ES: Yes. I think that along with the fear of pain, people are really afraid of becoming demented. The term dementia has been overused and sometimes misused in an insulting fashion. This frightens some people from either admitting that they have symptoms of cognitive disorders, or getting treatment for those symptoms. I think it's important to impress upon people that there are now treatment strategies available for many cognitive problems, and that early treatment improves the chances for recovery. DS: Could you help with some definitions? I think a lot of people are confused about the difference between myopathy and myelopathy, and between the central and peripheral nervous systems. ES: Central nervous system refers to the brain and spinal cord, and peripheral nervous system refers to nerves and muscles. Meningitis, encephalitis, myelopathy, cognitive disorders and infections like toxoplasmosis are diseases of the central nervous system; neuropathy and myopathy are diseases of the peripheral nervous system. It would be nice to have another word for myelopathy, which is spinal cord disease involving myelin, to distinguish it from myopathy, which is a disease of the muscles. DS: To make matters more complicated, myelin is a component of both the central and peripheral nervous systems, right? ES: Precisely. It's a covering around the nerve cell. One of the functions of myelin is to speed up transmission of nervous impulses. Demyelination can cause these impulses to slow or even stop. DS: Deciphering all these possibilities reminds me of the movie "Lorenzo's Oil." The medical and political dilemmas of Lorenzo's parents are amazingly parallel to what is posed by HIV. Some cognitive and motor lapses seem to be hard to distinguish from simple tiredness or preoccupation. How do you know when to be concerned? What are the clinical signs of HIV neurologic disorders that physicians and their patients should watch for? ES: It can be very helpful to first assess the stage of an individual's HIV disease. People with very high CD4 levels rarely get severe cognitive problems. They may have other neurologic problems, perhaps some unrelated to their HIV infection. Among the possibilities early in HIV disease are aseptic meningitis and some of the auto-immune neuropathies, like Guillain-Barr type neuropathy. Less frequently, we see some of the muscle diseases. Significant cognitive dysfunction is not frequently seen before the appearance of other signs and symptoms of AIDS, or before the CD4s (T-helper cell counts) fall significantly. But everyone should be aware of the signs of neurologic problems that prompt evaluation. Problems that develop slowly but daily are those such as balance difficulties, weakness or loss of feeling in the arms or legs, any loss of vision or the ability to communicate, a persistent loss or change in memory, concentration or attention. Someone having unexpected difficulty balancing their checkbook or remembering a frequently-dialed telephone number, or getting lost in familiar places, are examples of deficits that should be evaluated. Severe, persistent headaches should take you to an emergency room fast, especially if they are associated with fever, stiff neck, nausea or vomiting, or any visual symptoms. DS: Are the more gradual symptoms something that the affected person would notice? ES: Generally, yes. But in the case of behavioral or cognitive problems, it's often the affected individual's partner or family that notices changes. These can be somewhat difficult to differentiate from depression, or from some of the side effects of drugs, either prescription or street drugs. When people think of dementia, they may conjure up an image of someone like "Dr. Demento," or they may think of their grandmother who had Alzheimer's disease. People with AIDS dementia rarely look like this, especially in the early stages. First of all, people do not become demented overnight. It's a process that develops over weeks, if not months or years, and often will begin very subtly. Of course, early on is the best time to diagnose and treat it. The first thing many people start to notice is a persistent problem with memory, like retrieving words or names or associations. This suggests a subcortical problem, which primarily affects the inner part of the brain. It is very different from the situation with Alzheimer's, in which the cerebral cortex, the outer part, is impaired. In subcortical deficits, people can respond to cueing. In other words, if someone offers the person a hint, they can retrieve what they want to remember. Someone with Alzheimer's will not respond to cueing. HIV cognitive problems usually begin with a general slowing down -- not so much being different from your normal self. Reading, writing and understanding other people are not generally affected, until late in the disease. I compare early HIV cognitive problems to a record that's played at too few RPMs, whereas Alzheimer's is more like a record that starts skipping badly right at the beginning. DS: So HIV is not associated with the erratic behavior that people usually connect to the word "dementia?" ES: For the most part, no. In fact, it might have been easier to get funding for HIV neurologic research if people only displayed erratic and frightening behavior. Usually, people experience HIV-associated cognitive difficulties rather quietly. In most cases, especially in early stages, people rarely display grossly impaired judgment or odd behavior. It's really quite subtle, and can be overlooked by everyone, including the patient's doctor. It's very easy to attribute memory problems to depression, or medication, or having a bad day. There is a subset of patients who present with a more psychiatric picture of AIDS dementia. I emphasize that this is a relatively small group. We don't know what makes these individuals different from those with the more common picture of just slowing down. These people will present with psychiatric symptoms like mania, or with a delirium, in which they become acutely confused, wander around, do unusual and bizarre things. These people get identified very fast because they are troublesome to other people. But they hardly represent the majority of people with AIDS-related central nervous system disease. And of course, before you decided that this was dementia, you would want to know if they were doing any recreational drugs, or if they had an opportunistic brain infection, or if they had a history of psychiatric disease that was reactivated under stress. DS: Does dementia ever overlap with mental illness unrelated to HIV infection? I've known of people with a history of bipolar disorder [manic-depressive illness] which seemed to be exacerbated by HIV. ES: Yes. Many times people with a history of depression will have a new episode when they find out they're positive. And there's some research from Johns Hopkins University suggesting that bipolar patients are a bit overrepresented in AIDS clinics. There may be two types of problems here. There are those people with a history of bipolar illness, which then got a little more out of control with HIV. These situations are pretty easily controlled with medication. Then there are people with no personal or family history of mania or bipolar disease, who have very low CD4 cells, and who present with a manic-type picture. Often the mania responds to drugs, but then an underlying dementia reveals itself. This is usually seen in very sick patients, and it is not as common as persons with a single diagnosis of either manic-depressive illness or AIDS-related dementia. The average person with HIV cognitive problems does not usually get identified until they are quite advanced because they are not out there making problems for people. They are just slowing down, doing more poorly as time goes on. Often they are ill enough physically that they have already stopped working. I see a lot of people who have a minor cognitive or motor disorder. They are still working, often in professional jobs, often people who are quite bright, who are very quick to pick up on their cognitive dysfunction. They want to continue to participate in the mainstream of life as long as possible; they want any cognitive problems treated as early and aggressively as possible. DS: I understand that some important cells of the nervous system -- neurons in particular -- are not infected by HIV. So where does neurologic damage originate? ES: It would appear that in most adults HIV enters the nervous system at the time of initial infection. Usually there are no symptoms -- the virus is there but it doesn't do very much. We don't know exactly how HIV penetrates the nervous system, but we think one way it may get in is by hitching a ride on cells called monocytes, or macrophages, which can pass through the blood/brain barrier. Once inside, they infect other cells. The cells eventually infected are those that are not actually brain tissue. There are a lot of cells in your head that are not brain cells, per se. The cells like neurons, that do your thinking for you, and the oligodendrocytes, that make the myelin that surrounds the axons of neurons and help them conduct messages, do not appear to get infected with HIV, as far as we know. However, a lot of the supporting cells and scavenger cells in the brain -- macrophages, monocytes and microglia -- can be infected with HIV, and can actually live a long time with this infection. During this time, they can infect more cells, and can serve as a reservoir for HIV production. DS: If neurons and oligodendrocytes are saved from infection, what is it that can impair cognition? ES: We are still in the process of answering that question. We do know of several ways that the virus can indirectly injure those brain cells; in other words, affect them without infecting them. This is a new idea in neurology, and holds broad implications for treatment of other neurologic diseases. First of all, some of the individual component proteins of HIV, like gp120, appear to be toxic to neurons. These proteins can damage the neurons in a variety of ways. One of these is by opening up calcium channels, which neurons usually control to maintain a very specific balance. As calcium pours in, a process is initiated that, over a very long time, ends in cell death. The tat protein produced by HIV can also act as a neurotoxin. A second mechanism by which damage can occur is actually initiated by your own defenses. Your body's immune system responds to the presence of the virus by making cytokines. These are chemicals that immunologically activate cells and cell messengers, such as tumor necrosis factor, the interleukins and interferons. In fact we sometimes use cytokines as treatments for certain diseases. However, chronically high levels may cause cell damage. Tumor necrosis factor, for example, has been associated with damage to oligodendrocytes, the cells that make myelin. So having too much tumor necrosis factor may initiate demyelination. A third pathway for indirect damage to brain cells arises when the metabolism of normal compounds in the brain is disturbed by HIV infection. An example can be found in the transfer of amino acids from food digestion into the brain for the manufacture of neurotransmitters. These are substances that allow brain cells to communicate with one another. Without the right kind of balance of neurotransmitters, you see disturbances of mood, of thinking, of motor ability and sleep patterns, and so on. In HIV infection, several cytokines, including gamma interferon and tumor necrosis factor, can divert the metabolism of amino acids like tryptophan to make toxins like quinolinic acid. So there are at least three routes through which HIV can hurt neurons: toxic viral byproducts, excessive cytokine production, and derailed metabolism. All of these, separately and combined, can functionally damage neurons. In fact, quinolinic acid is actually synergistic with gp120. And in addition to all of that, there may be other substances that result from the HIV infectious process, like nitric oxide, prostaglandins, and leukotrienes -- basically the products of immune inflammation -- that could cause cell damage. DS: The next question, of course, is whether there are treatments to counter this damage. ES: Yes, the good side is that since neurons themselves are not infected, we can look for drugs, some of which are already available, to block some of the indirect injuries. There is even an assay, a way of screening drugs, to see if they have some potential to be effective in treating these problems. For example, we can grow certain kinds of brain-cell cultures, and add gp120, and add a drug, and see if the drug protects the cells. One of these drugs is nimodipine, which is a calcium- channel blocker, which blocks gp120-mediated calcium channel damage. Another is pentoxifylline, which may suppress the production of tumor necrosis factor. This may be a way of suppressing demyelination in the brain. A third drug is memantine, available now in Europe to treat Parkinson's disease. In test-tube cultures, memantine blocks the effects of quinolinic acid. Trials of nimodipine are already in process, and trials of pentoxifylline are set to begin soon. Memantine studies are still in the discussion stage. DS: What you said about cytokines reminds me of something Dr. Larry Waites has always maintained -- that AIDS is not an immune deficiency so much as a dysfunction of immune responses. ES: Correct -- I agree with that. I think that we had a very oversimplified view of AIDS in the beginning. We thought that HIV simply depleted the immune system, and if you could stop that process, the war would be over. In point of fact, one of the things that goes wrong in HIV disease is an overactivation, an inappropriate activation, of certain immune responses. So you have excess cytokines and inflammatory processes causing fevers, exaggerated allergic reactions, disturbed sleep, and wasting. DS: Would anti-inflammatory agents like aspirin be helpful? What about some of the other drugs discussed as treatments for cognitive disorders -- antiretrovirals, the amphetamines, the B vitamins, the "smart drugs?" ES: I'm not sure if anti-inflammatories are helpful. Concerning the antiretrovirals, AZT and ddI may have a protective effect against dementia. Two controlled studies, one of which will be published this spring, demonstrate that high-dose AZT, 1000 mg a day or more, can reverse many of the neuropsychiatric abnormalities in AIDS dementia patients. However, one problem is that only a fraction of the current antiretroviral drugs can cross the blood-brain barrier, and so very high doses must be sent through the bloodstream to obtain a positive neurological effect. You may end up bombing the village in order to save it, to borrow an image from the Vietnam War. Another avenue is to treat the symptoms. Some motor slowing can be reversed temporarily by the use of ritalin and other stimulant drugs. But this would be a poor choice of drug to give someone who was already manic. And these drugs do not make you smarter, they just make you faster and more functional. This is OK for getting to the bathroom, but not so much for driving a car. They will not improve your judgment. DS: So there is no therapeutic activity from amphetamines on the underlying problem, just improved function of the neurons that are already functioning. ES: Right. It's symptomatic treatment. DS: Why are B vitamins relevant? ES: In terms of B12, we clearly know that people with HIV frequently develop B12 deficiencies. These deficiencies, and others, may indeed play a role in demyelination. Unfortunately, you may have normal blood levels of B12 and other nutrients but not be getting enough to the brain because of a problem with the transport protein responsible for getting it there. DS: So it's possible that you could hammer someone with high-dose B12, and still not address the neuro deficiency because of this transport problem? ES: That is possible; the studies just haven't been done to prove or disprove it. DS: Speaking of metabolic pathways, what about the endocrine connection? It is known that certain hormones can function as neurotransmitters. I've long thought that the endocrine system and the nervous system were the great understudied areas of HIV research; maybe in fact they are a single area. ES: Absolutely ...the message of psychoneuroimmunology. It's very well-documented that in HIV infection, the hypothalamic/pituitary/adrenal axis is disturbed, and this may lead to very high levels of cortisol in the blood. We found that these levels are also high in the brain, and we know from research into other diseases that this may be bad for your brain cells. Cortisol may also exacerbate the damage caused by other neurotoxins. It's another instance of having too much of something that is usually a good thing. We found that when compared to people with HIV who were asymptomatic, people with AIDS dementia and other neurologic symptoms have high levels of cortisol and low levels of certain neurotransmitters in the spinal fluid. Imbalances of the neurohormones and neurotransmitters can be associated with dysfunctions of thought and mood and memory. This is an area that remains underexplored. In other diseases, we may not fix the original problem, but we control the symptoms. We don't know the precise cause of Parkinson's disease, for example. But we do know that there is a loss of a neurotransmitter, dopamine. So even though we can't cure Parkinson's, we have improved the life of people who have the disease by giving them drugs that will replace the dopamine in various ways. It may be that if we can identify some of the specific pathways or hormones or transmitters that are disturbed by HIV, and that contribute to neurologic disease, we can target drugs to relieve these symptoms. This could help people to remain functional and comfortable. DS: Can you identify an early cognitive deficit and treat it before it becomes disabling? ES: I have a patient who is ordinarily a very high functioning individual, someone who uses his brain a lot in a very productive job, and now he's having some cognitive problems. He certainly does not have dementia, but he has the potential to get there. At first the symptoms were controlled with high-dose AZT, and he had a great year and a half. Then we had to slow down the dose to 400 mg a day because he developed some medical problems from so much AZT. As soon as we did that, his neurological functions got worse again. We're going to try other antiretrovirals, or nimodipine. But the point is, he is really upset and feeling like he's the only person in the world in his situation. I think there has been a lack of attention to the needs of these people. Perhaps this stems from the social misconceptualization of dementia, of drooling people rummaging through garbage cans. But my patient is more representative of people with cognitive disorders: people who are functioning below their baseline, who are worried about getting worse because they want very badly to keep working. There hasn't been much of a push from the scientific community or the activist community for practical, clinical treatments for cognitive problems, except for peptide T. The ACTG trials have run into a lot of red tape and trouble with funding. And I think there is a lot of embarrassment and confusion in the community about cognitive problems in HIV disease. This may be a response to the reactionaries out there who suggest that everyone with AIDS is demented, which is not true, or that all people with cognitive difficulties cannot take charge of their own lives, which is not true. So in reaction, you end up with other people saying that the problem doesn't occur, or it doesn't occur very much, or it only happens to people who are about to die. In the middle of these extreme positions, meanwhile, are patients who have cognitive symptoms but don't have much support from either their community or the medical establishment. I feel very frustrated that there are agents out there which might help my patients, but have not been tested. The incidence of people whose first AIDS diagnosis is dementia may be only 7%. But that goes up another 7% a year in people who have had some other AIDS-index diagnosis. So this is going to become a bigger issue as people live longer. I'll put a question to you: why do you think dementia has been an underserved and ignored area? DS: Well, I think you're right about the "embarrassment" of dementia, and about mental status problems generally. If you address them, then you allow for their existence, which allows for their potential to target you. I also think that the specter of "losing your mind," however inflated, is really draining to face for people who already face the loss of their physical health, and who in the past have come perilously close to losing legal and civil rights. I do know people in ACT UP New York and ACT UP Golden Gate who have seriously tried to get more research attention for dementia. [For coverage of activist efforts, see AIDS TREATMENT NEWS issue number 156, August 7, 1992.] If more people did make waves for HIV cognitive research, and if Hillary Clinton gave you half a zillion dollars for this research, where would you start? ES: First of all, that kind of money should be distributed to research for everyone at risk for dementia. People with money and education usually tend to get better care, and poor people tend to get neglected. Also, neurologic diseases are more common at the extremes of life, which is also where people get ignored a lot. You're more likely to experience neurologic disease if you are very young, or older. I would like to see more money for clinical trials of symptomatic treatment of neurologic disease -- not just dementia, but also neuropathy, pain, headaches, depression and sleep disorders. I'd like to see a balance between basic molecular biology and meeting the immediate needs of my patients. DS: But those interests should converge! ES: They should, but right now they're not. I'd also like to have some better methods of drug delivery -- how to get enough drug into the brain without flooding the rest of the body. DS: What about intrathecal administration [injecting drugs directly into the cerebrospinal fluid], or liposomal preparations [drugs encapsulated in liposomes]? ES: The intrathecal route has been tried, but it's fraught with medical complications, and it's expensive. It may be a solution for a very few people, but this is not a problem that applies to just a few people. I don't know enough about liposomal drugs. It worked for amphotericin, so it's an interesting question. We need to get the funding to answer those kinds of questions. DS: Or even to get the questions asked. ES: Yes. And one of the most important questions concerns the very direction of HIV drug research. You could come up with the best antiretroviral for the body, but if it doesn't effectively penetrate the blood/brain barrier, you're going to end up with the brain as a safe reservoir for viral replication, a constant source of reinfection. Also, we should ask why some people with HIV develop neurologic problems, and not others. The answers to these questions can't all be with the virus. Some of the answers are in the host, in people living with HIV. Note: Dr. Singer will speak at St. Mary's Hospital in San Francisco on April 7, 5:30 p. m., at Morrissey Hall, 450 Stanyan St. (near Hayes), at the AIDS Grand Rounds of the Community Consortium. ***** Eyesight, Hearing, Speech: Potential for Rehabilitation Often Ignored When Treating AIDS by Dave Gilden CMV retinitis damages the eyesight of about a quarter of the people with advanced AIDS. Several studies have found that up to half the people with AIDS experience at least slight hearing loss. A wide range of conditions, many stemming from medical treatments, also can interfere with the ability to speak. Yet scant attention is paid to the personal consequences of losing connection with the outside world. Physicians tend to focus on treating their AIDS clients' diseases and know little about teaching them to cope when disabilities nevertheless occur. A large network of organizations serving disabled individuals has tremendous expertise on the subject of rehabilitation, but it has had little contact with the AIDS community. A one-day conference on HIV-related speech, hearing, and vision loss last month at the University of California San Francisco sought to bridge this gap by bringing together the specialists who could restore quality of life and dignity to those surviving advanced AIDS. People confronting loss of vision, hearing or speech without help or preparation can sink into deep depression and lose their interest in living. Fortunately, a systematic approach to such problems can alleviate them. The attack is three-sided, involving treatment, education, and mechanical assistance when necessary. Rehabilitative approaches have to take into account not just specific diseases, but a patient's overall health, personality and past history. Sight CMV retinitis is the most common source of AIDS-associated sight loss. Brain tumors arising from lymphoma and KS lesions on the eye or eyelid also impair vision in people with AIDS. At the conference, San Francisco ophthalmologist Robert Neger, M. D., noted that due to medical advances, "the average life expectancy for someone with CMV used to be three months. Now people frequently live for two years and sometimes longer." The introduction of ganciclovir and foscarnet has considerably improved the treatment of CMV, but the two drugs only halt the advance of the disease. Recurrence is possible as survival time grows. In addition the drugs' side affects are severe, and their daily infusion through a permanently implanted catheter is onerous. According to Tom Gaughan of the Rose Resnick Center for the Blind and Visually Impaired, treatment issues are one important reason to join a peer support group for those with AIDS- associated sight loss. Treatment difficulties are just the first set of issues, though. Visual deprivation creates dependencies that can severely strain personal relationships. People have to develop new social as well as practical skills to ensure that their needs are met. At the same time, visually impaired individuals with AIDS generally have reduced mental and physical stamina. They may not have the strength by themselves to both cope with their loss and develop the skills needed to use the wide variety of devices available to assist those with low vision. Such devices range from specialized eyeglasses and large screen computers to canes and guide dogs. David Custead, who completely lost his sight almost three years ago as a result of CMV said, "I've been through five life-threatening diseases. Eyesight is now a minor part of my life, but it would have been good to get help ahead of time." It takes a particular sensitivity and knowledge to assist people with AIDS who are losing vision. Tom Gaughan has offered to assist people in finding such help. His telephone number is 415/441-1980. Hearing Most of the hearing loss arising from AIDS-associated ear infections is reversible, especially if treated promptly. (Note that if not treated promptly, microbes like pseudomonas and aspergillus can spread to the skull base, damaging cranial nerves with possibly fatal results). In contrast, hearing loss may also be an irreversible consequence of some antibiotics, such as amikacin and clarithromycin (both used for treating MAC). Other sources of permanent hearing loss include neurosyphilis, HIV- associated damage to the auditory nerve, and brain tumors. Our visually oriented society tends to belittle the importance of hearing, and frequently ascribes hearing complaints to psychological origins. The problems are serious, though. "Losing your hearing as an adult is like losing a close friend. You go through a grieving period," commented Robert Arden, a person with AIDS who became deaf two and a half years ago. Arden lost his hearing in one ear two years before his second ear abruptly stopped functioning. Yet he had no preparation for deafness because his doctor told him complete hearing deprivation was unlikely. Obviously, it is strongly desirable to start communication training ahead of time. Hearing aids are available for those with only limited difficulty, and there are speech reading and sign language classes at local centers for the deaf for those with the health and energy to participate in them. Once again, support groups can make a major contribution to resolving psychosocial issues. The location of resources for those with AIDS-related hearing loss may be obtained from Karen Rachel at the San Francisco Hearing Society (415/863-4710, TDD: 863-2550, fax: 863-2715) or Florrie Burke at the University of California Center on Deafness (415/476-4980, TDD: 476-7600, fax: 476-7113). Speech Impairment Speech is such a complicated physical/mental process that many conditions can obstruct it. These include strokes, oral and esophageal lesions, respiratory weakness, and lack of muscle coordination caused by thorazine and related tranquilizers. Also, feeding tubes and respirators will block speech. There are many speech therapists who can advise clients of long term and temporary measures that at least ameliorate speaking disturbances. Exercises are helpful for certain problems, especially those involving swallowing disorders. Mechanical devices, such as electronic larynxes and hand-held printers, can benefit even patients requiring respirators or tracheotomies to breath. These devices are rather crude and fatiguing, though. A pen and pad of paper often is still the cutting-edge technology. Training caregivers to assume more of the burden of communication is a necessity when people have speech difficulties. Bridging the communications gap is vital for discovering people's needs when they are sick. As people with AIDS live longer due to improved medical management, more will enter that confusing and frightening world of communications and sensory impairment. The conference at the University of California, the first of its kind in the nation, was an initial step in preparing care providers (and payers) for the steps needed to maintain patients' capabilities. ***** Notes ** Alpha-APA Derivative R89493: Technical Article Published In September 1992 AIDS TREATMENT NEWS published a short report about a new class of drugs called Alpha-APA derivatives, developed by the Rega Institute for Medical Research and the Janssen Research Foundation, both in Belgium. We reported that one member of this class, R89439, had been tested in a few people and had been selected for phase I/II trials. R89459 is a non-nucleoside RT (reverse transcriptase) inhibitor. Other experimental drugs with a similar mechanism of action are nevirapine (BI-RG-587), and pyridinone (L-661) [see "Convergent Combination Therapy," AIDS TREATMENT NEWS #170, March 5, 1993]. These drugs are unlikely to work alone, because viral resistance can develop rapidly; but they may be useful in combination therapies. And, contrary to some earlier beliefs, the different drugs of this class are not equivalent in terms of resistance; viruses which are resistant to one can be still be susceptible to another. Therefore, it is important that different drugs of this type be tested. One potential advantage of alpha-APA is that it could be manufactured inexpensively enough to be affordable in any part of the world. ("Underground" drug could be dangerous, however, as at least one of the starting ingredients, sodium cyanide, is very poisonous.) Until recently, only short conference abstracts on alpha-APA have been published. A longer paper appeared in the current (March 1993) Proceedings of the National Academy of Sciences, USA [Rudi Pauwels and others, "Potent and Highly Selective Human Immunodeficiency Virus Type 1 (HIV-1) Inhibition by a Series of Alpha-Anilinophenylacetamide Derivatives Targeted at HIV-1 Reverse Transcriptase," pages 1711-1715]. ** Searchlight, March/April 1993 The March/April issue of Searchlight (the newsletter of SEARCH Alliance, a community-based research organization in Los Angeles) has several useful articles -- especially one on nutrition, and one on the scientific background of ribozymes (a kind of high-tech antiviral, called "molecular scissors" in the newspapers a few weeks ago). The nutrition articles, based on the presentations of several experts who spoke at a January symposium in Los Angeles, focus on the importance of early nutritional and other intervention to prevent the loss of body mass. The presentation includes phone contacts and other suggestions for finding more information. Other articles concern shark cartilage ("does not look promising"), CD8 expansion, trials run or being planned by SEARCH Alliance, and "treatment briefs" on experimental therapies in the news. Searchlight is available without charge from SEARCH Alliance, 7461 Beverly Blvd., Suite 304, Los Angeles, CA 90036; you can obtain a copy by calling 800/64-SEARCH, or 213/930-8820. Searchlight is also available online by computer; call SEARCH Alliance for more details. ***** AIDS TREATMENT NEWS Published twice monthly Subscription and Editorial Office: P. O. Box 411256 San Francisco, CA 94141 800/TREAT-1-2 toll-free U. S. and Canada 415/255-0588 regular office number 415/255-4659 fax Editor and Publisher: John S. James Medical Reporters: Jason Heyman John S. James Nancy Solomon Reader Services and Business: David Keith Thom Fontaine Tadd Tobias Rae Trewartha Statement of Purpose: AIDS TREATMENT NEWS reports on experimental and standard treatments, especially those available now. We interview physicians, scientists, other health professionals, and persons with AIDS or HIV; we also collect information from meetings and conferences, medical journals, and computer databases. Long-term survivors have usually tried many different treatments, and found combinations which work for them. AIDS Treatment News does not recommend particular therapies, but seeks to increase the options available. Subscription Information: Call 800/TREAT-1-2 Businesses, Institutions, Professionals: $230/year. Nonprofit organizations: $115/year. Individuals: $100/year, or $60 for six months. Special discount for persons with financial difficulties: $45/year, or $24 for six months. If you cannot afford a subscription, please write or call. Outside North, Central, or South America, add air mail postage: $20/year, $10 for six months. Back issues available. Fax subscriptions, bulk rates, and multiple subscriptions are available; contact our office for details. Please send U. S. funds: personal check or bank draft, international postal money order, or travelers checks. VISA, Mastercard, and purchase orders also accepted. ISSN # 1052-4207 Copyright 1993 by John S. James. Permission granted for noncommercial reproduction, provided that our address and phone number are included if more than short quotations are used. &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& End of display -- ben@maggadu.QueerNet.ORG AIDS Info BBS 415)_626-1246 free since July 25, 1985