Contents

• Depression and HIV: Assessment and Treatment
• Food, Fitness and HIV: The Connection
• Immune Modulation Therapy with IL-2 and IL-12
• Notes From the 4th National Conference on Retroviruses and Opportunistic Infections
• Helpful STEP Fact Sheets Available!
• Free Classes: Learn HIV Survival Strategies
• AIDS Survival Progress
• Clinical Trials and Studies Seeking Patients

Depression and HIV: Assessment and Treatment by Andrew Elliot, MD Madison Clinic at Harborview Medical Center University of Washington Department of Psychiatry and Behavioral Sciences

With the advent of protease inhibitors for the treatment of HIV infection, the media has asked, "How will the AIDS culture...deal with...a chronic manageable disease?" Is it a chronic manageable disease? Certainly, the presence and availability of protease inhibitors has and will change the face of HIV infection now and in the next few years. Thus, changes in the treatment of HIV/AIDS can affect one's outlook and life perspective. With respect to these new treatments, one faces many questions. Should I take them, and at what point in the course of infection? Are they available to me? What will they do to my life? Will I feel better, and what happens if I feel much better? Should I go off disability? Or will I be unable to tolerate them and then...feel worse? While these are only a few questions that may arise with new treatments, they may evoke a myriad of feelings including helplessness, loss of control, rejection, hopelessness, isolation, withdrawal, anger, sadness and fear. These feelings may precede or become what is known as depression, or in clinical terms, a major depressive episode. With changes in treatment, many people may experience these feelings with the multiple losses of control that occur in the context of HIV infection. One might naturally assume that HIV-infected individuals would 'naturally' become depressed upon learning of their infection or upon the realization that they are unable to tolerate a protease inhibitor. Studies have investigated this, and although there have been no large-scale epidemiological studies, as with many chronic illnesses, this is not the case. What is Depression? The diagnosis of depression is based on a minimal duration of certain groups of symptoms. A major depressive disorder is diagnosed when one has several of the symptoms in Table 1 (see end of article) which last for at least 2 weeks and include the presence of 1 or 2 symptoms (or both). An untreated episode typically remits within 6-12 months. Chronic mood depression (for most of the day, more days than not) that persists for at least two years and is accompanied by the symptoms above is diagnosed as dysthymia. Some individuals have chronic depression (dysthymia) with episodes of depression superimposed on top of it. This is called "double" depression. Depression and HIV Infection Cross-sectional and prospective studies in both HIV+ and at-risk HIV populations estimate lifetime prevalence of depressive disorders to range from 22.1 - 61.0% with 6 - 12 month (current) prevalence ranging from 0 - 18.4% in HIV positive and 0 - 9.1% in HIV seronegative populations. These rates are all elevated when compared to estimates of lifetime (5% and 17%) and current (3% and 10%) diagnoses of major depression in community samples. Depression appears to be the most common psychiatric disorder found among HIV-infected individuals. Depression has a significant effect on quality of life, progression of disability and ability to receive good medical care. With the advent of protease inhibitors, which have the potential to control HIV infection and prolong life, treatment of a major depressive disorder is even more critical, since untreated depression could both compromise medication adherence and potentiate the disabling effects of the illness. Preliminary evidence also suggest that chronic depressive symptoms may be associated with increased mortality in HIV positive patients. It has been suggested that HIV itself causes depression, that HIV associated neurocognitive changes (now referred to as Minor Cognitive Motor Disorder and HIV Associated Dementia) may be a cause of depression, or that HIV associated medications (including AZT) may cause mood changes. There are a few case reports which address these issues, but there is little evidence to support these hypotheses. Many depressive symptoms are difficult to assess in HIV/AIDS population. This is often related to clusters of physical symptoms that are associated with HIV-related medical illness or psychological symptoms such as anxiety or loss of interest in activities when the person has been bedridden, housebound, or unable to participate in social and recreational activities. In early stages of HIV infection, these symptoms rarely coexist with depression. However, as HIV infection progresses, physical symptoms can be clearly attributable to HIV itself, thus making it difficult to separate from a depressive disorder. In these cases, it is important to rule out causes of physical illness. The provider should then review the symptoms present, rule out other causes, and consider the prominent symptoms. When other causes have been ruled out, depressed mood is most often the prominent symptom. Treatment of Depression in HIV infection Many treatment options are available. Individuals who are experiencing any or some of the symptoms listed in Table 1 should consider seeking further evaluation and treatment via their primary care provider. Two recent studies looked at depressive symptoms over time and noted an association with progression of illness. This has yet to be substantiated, but suggests that treatment of depressive symptoms may affect survival. The most effective methods of treating depression include a combination of counseling (psychotherapy) and medication. Psychiatrists, psychologists, nurse practitioners, and social workers all provide different forms of treatment for depressive disorders. Psychotherapy Psychotherapy or counseling in HIV+individuals has been approached from several models including supportive, cognitive behavioral therapy (CBT), interpersonal therapy (IPT) and group therapy. Common themes for clients during therapy are loss of relationships and autonomy, employment, physical well-being and appearance, fear of neurologic problems, spirituality as well as stigma and discrimination. All forms of therapy involve supportive elements that play a role in the success of the therapies, but supportive and insight-oriented therapy define support as paramount. Not only is the supportive relationship between therapist and client a vehicle for exchange of information between client and therapist, but the relationship itself is of therapeutic benefit in a variety of ways. IPT has been studied in outpatient HIV+ individuals with Major Depression. In these people, it helped relate changes in mood to changes in their environment or in role changes. The therapist engages the client in their emotional life issues, conceptualizing difficulties within one of four interpersonal problem areas: grief, role dispute, role transition, or interpersonal deficits. The therapist then uses specific strategies to deal with the problem areas, focusing on the here and now, on what the client wants to achieve, and on what options exist to achieve it. In contrast, CBT is based on the philosophy that depressed people distort reality in a particularly negative way. CBT involves setting goals, defining target symptoms, problem solving, investigating relationships between thoughts and emotions and their underlying assumptions. As well, in the context of CBT, self-defeating behaviors and interpersonal and coping skills are often addressed. For example, a CBT therapist would challenge a HIV+ person's view that their life is hopeless, believing that people have the capacity to construct a positive sense of the future. The CBT therapist would engage the client in an effort to identify hypotheses which would support or reject their beliefs. Group therapy has been used extensively with HIV+ individuals in a variety of contexts and is highly efficient. It provides psychoeducation, confrontation regarding mispercetions about the illness, and shared experiences, all of which help to improve peoples' mood and quality of life. Pharmacotherapy The approach to pharmacotherapy for HIV+ individuals with a major depressive disorder may be slightly different than for the general adult population. HIV+ individuals often respond differently to medications, often being more sensitive, and may need a "start low and go slow" approach. As well, individuals with advanced HIV infection are often on multiple medications which increase the probability of drug-drug interactions. Additionally, side effects may occur differently, with some being helpful and some aggravating current symptoms of HIV infection itself or HIV-related illnesses. There are few controlled studies which have evaluated the efficacy of antidepressant medications in HIV+ individuals. Several open trials have looked at efficacy of a few other antidepressant medications, however, their data is confounded by the complicating effects of medical illness as well as separation of drug-placebo differences. And, more recent studies have alluded to the important relationship between tolerability and efficacy in this population. Major depressive disorder in people with HIV infection has been effectively treated in open trials with fluoxetine, imipramine, sertraline, fluvoxamine, methylphenidate, desipramine and testosterone. Of these, only two (imipramine and paroxetine) have been investigated in randomized placebo-controlled trials. Imipramine demonstrated an effective antidepressant response that was similar to that seen in medically healthy depressed people and unrelated to the severity of immunosuppression. A high rate of imipramine discontinuation in this trial, coupled with open trial reports of mild and infrequent side effects for fluoxetine and sertraline (although not fluvoxamine) was found in depressed HIV positive people. This suggests that fluoxetine and sertraline (both known as selective serotonin re-uptake inhibitors), although not more efficacious, may be more tolerable and have increased overall effectiveness in this population (a higher proportion of treated who benefit). Paroxetine was subsequently compared to imipramine in a double-blind placebo-controlled trial and found to validate what was previously hypothesized: SSRIs (fluoxetine, paroxetine, sertraline) are more tolerable with fewer side effects and thus may be more tolerable leading to an increased overall effectiveness. Testosterone replacement has been shown to improve depressive symptoms in individuals with low testosterone levels, especially for those with decreased libido or sexual dysfunction. Before administered, a clients' testosterone levels should be checked. Additionally, stimulants have been shown to improve mood, energy and alertness and to be effective in medically ill populations. There have been several open trials which used stimulants and have suggested that people benefit from stimulants with decrease in depression and cognitive deficits. It is important to note that stimulants have side effects which include insomnia, agitation, weight loss, and paranoid ideation. In addition, tolerance may develop after initial benefit. There have yet to be significant randomized, placebo-controlled trials which more thoroughly evaluate stimulants against other antidepressants with respect to tolerability and overall efficacy. Side effects and tolerability are important aspects to treatment in the HIV+ client. People may have many concerns including loss of control, the focus on identifying somatic symptoms which may indicate physical illness and sexual dysfunction which all effect how they tolerate a medication. The provider initiating antidepressant treatment should consider their client's HIV-related symptoms when selecting an antidepressant. TCAs may be more sedating, and may be helpful for insomnia. Their anticholinergic side effects may be effective for managing chronic diarrhea. On the other hand, TCAs may be more effective in managing a person with concurrent HIV neuropathy to treat neuropathic pain in association with depression. SSRI antidepressants are not usually sedating and can cause nausea and exacerbate chronic diarrhea or may have sexual side effects, but may alleviate chronic constipation. Stimulants may increase cognitive processing, but can cause agitation and weight loss. The newer antidepressants including, venlafaxine, nefazodone, and mirtazapine have yet to be investigated in open or randomized, double-blind trials. They have different side effect profiles than both the TCA's and SSRIs and may be especially helpful in patients attempting to avoid specific side effects or combat physical symptoms of HIV or HIV-related illnesses. Venlafaxine has properties of both TCAs and SSRIs and may be useful if these side effects are avoided with low doses. Nefazodone has no reported sexual side effects and although it is known to cause dry mouth and dizziness upon initiation of therapy, these are often easily tolerated. Mirtazapine may be useful in people who are experiencing insomnia and could benefit from weight gain, in that it both stimulates appetite and increases weight. These, as with both the TCAs and SSRIS, all need to be evaluated in the context of the individual's current HIV-related symptoms and how they are affecting their quality of life. SSRI and newer antidepressant medications have several advantages over TCAs for people with HIV illness. They are likely to be better tolerated with fewer side effects, leading to a lower incidence of side effect related dropout and increased compliance with treatment. As a result they are likely to be more effective in treating depression. They are not sedating and lack the anticholinergic side effects seen in TCAs. Therapeutic dosing is easier and often allows management by the primary care provider. Clients should be educated about the length of time it takes for antidepressant response (often 3-4 weeks) and about common side effects one might experience with a particular antidepressant including how this may affect their HIV illness. Finally, it is especially important to reinforce compliance by arranging contact with the client within a brief time after initiation of therapy in order to evaluate side effects, treatment effect, and patient expectations. Table 1. Symptoms of a Major Depression Depressed mood most of the day, nearly every day. Diminished interest or pleasure in all or most activities. Increased or decreased sleep nearly every day. Fatigue or loss of energy nearly every day. Loss of appetite or weight. Insomnia or increased sleep. Feelings of worthlessness or excessive or inappropriate guilt. Decreased ability to concentrate. Agitation. Recurrent thoughts of death, suicidal thoughts or suicide attempt. Feelings of hopelessness. Adapted from the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), 4th edition. Washington, DC: American Psychiatric Press 1994:327. Risk factors for Major Depression in HIV+ or At-Risk Populations Previous depression or family history of depression Alcohol, IV drug or other substance use Loss of social supports Multiple losses Common Conditions Mimicking Depression Pneumocystis Shortness of breath, lethargy, fever, cough Toxoplasmosis Headache, depression, social withdrawal Cryptococcal Meningitis Headache, fever, depression HIV Associated Dementia Memory loss, social withdrawal, personality change Lymphoma, PML Withdrawal, depression, focal neurologic changes Treatment Options Psychotherapy Supportive Interpersonal Cognitive-Behavioral Group Pharmacotherapy Antidepressants Stimulants Testosterone Combination Therapy Psychotherapy+Medications Types/Classes of Antidepressant Medications Tricyclics Amitriptyline, Nortriptyline, Desipramine, Imipramine Bicyclic Venlafaxine SSRI's Paroxetine, Sertraline, Prozac MAOI's Parnate, Nardil Other Wellbutrin, Nefazodone, Mirtazapine, Trazadone Approach to Pharmacotherapy with Anti-Depressants in HIV+ Infection Rule out causes of medical illness that may present as depressive symptoms Review all currently prescribed medications. Evaluate for any possible drug-drug interactions Address issues of alcohol and substance abuse/dependence Consider how the individual currently tolerates medications (e.g. sensitivity to side effects) Selective sertonin reuptake inhibitors (SSRI's) or newer generation antidepressants (nefazodone) with fewer side effects may provide equal efficacy and increased tolerability as compared to tricyclic antidepressants (TCA) The presence of depression and weight loss may indicate use of mirtazapine (Remeron) which both stimulates appetite and increases weight The presence of depression and neuropathy may indicate the use of TCAs, as these may augment neuropathic symptoms In advanced HIV infection, as in other chronic illnesses, stimulants may improve mood, energy, an alertness and cognitive ability Additionally, for those people with low testosterone levels, testosterone replacement may improve depressive symptoms Educate the client about the course of depression, treatment response and side effects History of previous depression and treatment resistance may suggest maintenance therapy Sidebar: Protease Inhibitors & Antidepressants Of the FDA approved protease inhibitors, ritonivir (Norvir) may be the most potent inhibitor of the drug metabolizing system referred to as the cytochrome P-450 system. It is a collection of enzymes which metabolize many of the natural chemicals and medications in your body. Many HIV-related medications inhibit these enzymes, including ketoconozole and the protease inhibitors. The protease inhibitors are known to inhibit specific groups of enzymes referred to as the 3A group. While ritonivir and indinavir are known to potently inhibit the 3A system, not all protease inhibitors have the same specificity for these systems. Several antidepressants are metabolized through one or more of the cytochrome P-450 enzymes including fluoxetine, fluvoxamine, paroxetine, nefazodone, and tricyclic antidepressants. Levels of those antidepressants which are metabolized by the 3A system may be increased when protease inhibitors are administered concurrently, which in turn are experienced by the client as side effects and may be misinterpreted as a change in medical illness state leading to medical evaluation or hospitalization. People at increased risk of drug interactions include: those who are on multiple medications, and have multiple medical illnesses; those with deficiencies in one or more cytochrome P-450 enzyme system; people with renal and hepatic disease; those who are elderly and or physically debilitated; or those people who are on single potent enzyme inhibitors such as the protease inhibitors. Prescribing providers should carefully evaluate clients on protease inhibitors for possible drug interactions and side effects. Selected References Markowitz JC, Klerman GL, et al.: Individual psychotherapies for depressed HIV-positive patients. Am J Psychiatry. 1995; 152:1504-1509. Mayne TJ, Vittinghoff E, Chesney MA, Barrett DC, Coates TJ: Depressive affect and survival among gay and bisexual men infected with HIV. Arch Intern Med 1996; 156:2233-2238. Wagner GJ, Rabkin JG, Rabkin R: A comparative analysis of standard and alternative antidepressants in the treatment of human immunodeficiency virus patients. Comp Psychiatry 1996; 37:402-408. Vitello B, Stover ES: Psychopharmacology in HIV-positive patients: research perspective. Psychopharmacol Bull 1996; 32:293-297. Markowitz JC, Rabkin JG, Perry SW: Treating depression in HIV-positive patients. AIDS 1994; 8:403-412. Nemeroff CB, DeVane CL, Pollock BG: Newer antidepressants and the cytochrome P450 system. Am J Psychiatry. 1995; 153:311-320.

Food, Fitness and HIV: The Connection by Sabina Beesley, MS, RD Chicken Soup Brigade and Joanne Maurice, MS, RD Madison Clinic, Harborview Medical Center

Once diagnosed with HIV, the fear of wasting away becomes very real. Wasting means losing a lot of muscle which makes you weaker and sicker. If you know how to avoid it, you can stop it. This article will let you know what to do. By avoiding losing muscle and weight, you will give yourself the best chance to respond to all the new treatments fighting the HIV virus. There are two steps you can do today to avoid muscle wasting: Eating and exercising. Eating enough food will maintain your muscles and weight, while exercise builds more muscle. It is that simple. STEP 1: Eat Enough Food Small Frequent Meals: Eat throughout the day. Small frequent meals are the way to go. Most people find eating 3 meals and 2 snacks each day fits well into their schedules. Eat by the clock; don't wait to get hungry to eat. High Calorie and High Protein Foods: Eat mostly high calorie, high protein foods which will fuel your muscles and help you stay strong. The HIV virus makes you burn a lot of energy, so you can pig out without feeling guilty as long as you pig out with healthy foods. Here's how. Eat from all the food groups below to make sure you are getting all the energy, protein, vitamins and minerals you need. Starches Bread, rice, pasta, cereal, potatoes, grains. Eat 4 or more servings daily. Each serving is 2 slices of bread or 1 cup of pasta, rice, cereal, potatoes, etc. These foods give you energy. Proteins Meat, fish, chicken, tofu, eggs and beans. Eat 2 or more servings per day. If you are a vegetarian, eat 4 servings of protein each day. Each serving is a 1/2 cup or 3 ounces of meat (half the size of your palm). Protein give your muscles fuel. You can use protein powders as a supplement to your diet but don't rely on them as your only source of protein since they are not absorbed into your system as well. Dairy products/ Dairy substitutes Milk, yogurt, pudding, ice cream, cottage cheese, Enriched rice or soy milk, TUMS or calcium supplements. Eat 2 or more servings daily. Each serving is 1 cup, 1 ounce cheese (size of your thumb) or 2 TUMS or other calcium supplements per day. Dairy products or enriched dairy substitutes give you calcium which your muscles, brain and nerves need to work. Fruit/vegetables Apples, oranges, tomatoes, broccoli, greens, etc. Eat at least 3 times a day. Each serving is 1 piece of fruit or 1/2 cup of vegetables. Fruits and vegetables give you vitamins to help fight off infections. Fats and sweets Oil, butter, gravies, mayo, sugar, candy, cakes, chocolate. You can eat as much as you like as long as you eat enough from the other food groups and you are not over weight ( Do not eat a lot of fats and sweets if you are more than 40 pounds over weight). Fats and sweets give you concentrated energy. Beverages Water, juice, pop, nectars, herb teas. Drink at least 8 cups a day. Coffee and tea are fine as long as you don't drink more than 4 cups a day. Coffee and tea do not count as a beverage since they dehydrate you. Don't drink any alcohol if you are on medications since it can severely damage your liver. When your liver doesn't work neither do medications. You may feel that this is more food than you can handle each day but if you space it out through the day with 3 meals and 2 snacks per day it can be done easily. The trick is to eat several times a day and never get too full at one time. See sample menu below. BREAKFAST 2 eggs/1 slice of toast with butter/herb tea or juice SNACK cheese and crackers/1 cup juice LUNCH 2 cup juice/pop/Peanut butter and jelly sandwich/4 Fig Bars SNACK Candy bar/2 cups juice DINNER Turkey Sandwich/1 cup Cream of Mushroom soup/Pudding/2 cups juice Bottom line Whether you are living with HIV or AIDS, you have an unlimited amount of options of what you can eat. From a nutritionist's standpoint you can eat whatever you want as long as you eat enough calories, protein, vitamins and minerals. What you specifically eat is not that important. The next step to avoid wasting is to exercise, follow the guidelines below. Step 2: Exercise You say that you don't have a butt any more? Have your muscles started to shrink right before your eyes? DON'T PANIC! It will take a little work on your part in the form of exercising, but you can look good again. Why should you consider exercising at all? First and most importantly, there are several studies that show exercise has a positive effect on the immune system and quality of life for people with HIV. Studies have shown that CD4 counts go up when people do simple, consistent exercise. Also, exercise will give you more energy and perk up your appetite and sense of will being. This lets you eat more and avoid wasting. If you start working on it now, by the time it is shorts weather you should be looking buff again. There are two parts to bulking up: 1) eat the right amount of calories and protein to help build muscle and 2) do the right type of exercises to increase those all important muscle groups. If you have been a die hard couch potato, start slowly, or your muscles will ache from overexertion. If any kind of exercise routine is new to you, start by doing some simple stretches while on the couch or before you get out of bed. Start with a whole body stretch by extending your arms over your head, s-t-r-e-t-c-h as you exhale. Next, bring your knees toward the chest with the hands grasping your legs just below the knees. Lengthen your neck and look straight up, breathe deep in and out a few times holding that position. You can alternate the legs, hugging one a time to your chest. With any stretching routine that you do, exhale as you stretch and inhale as you move into a new position. Stretch until you feel tension, then hold the position for 10 to 30 seconds. Don't jerk or bounce through any movements. For some simple muscle building exercises try these ideas. Push-ups- yes good old-fashioned push-ups are wonderful for bulking up those arms. If it has been awhile since you have done a military press, start by doing push-ups against a wall, or by placing your hands on a counter. Start with doing 15 to 20 push-ups, keep adding a few more each day until you have reached 100 or more. To work the abs, do some crunches. Start with 10 or 15, remember to just raise your shoulders off the ground. Work up to doing several repetitions of 40 - 50 each. To work the thighs, place your back against a wall with your feet about 15 inches out from the wall, move down until you are in a sitting position. Keep your back pressed against the wall. Hold that for 30 seconds and work up until you can do several minutes. This series of 3 exercises initially will take you about 10 to 15 minutes a day. Being creative with this will make it fun. Exercise with a friend, do it to your favorite music, do it while you watch TV, but just get off that couch and do it! There are several good books at the library or bookstore on how to exercise to build muscles or lose weight. Full Circle Fitness by Rebecca Eastman is very basic with simple illustrations and guidelines for exercise routines to follow. There are multitudes of videos you can buy or check out. Make sure that you find one on strength training, not aerobic exercise which is meant to help you lose weight, not add muscle. Summary Eating enough and exercising for at least 15 minutes each day is a great immune booster. Food, exercise and medicines all support your body's fight against HIV. You can't rely on just one or two, they work best as a team. MAKE A COMMITMENT TO YOURSELF FOR HEALTH!

Immune Modulation Therapy with IL-2 and IL-12 by Lisa Boonprakong

From examining the human immune system, scientists have characterized a number of chemical " messengers. " These messengers play a fundamental role in directing a variety of necessary paths in the body's natural response to the invasion of organisms and pathogens which include HIV. In particular, one group of chemical messengers more definitively defined as cytokines, are hormone-like proteins which govern cells of the immune response. Naturally produced in the body by certain white blood cells of the immune system (such as T-helper/CD4 cells), cytokines are an essential link in the communication between cells of the immune system and of the rest of the body. A number of cytokines have been identified and characterized; however, not all of their effects are known. Yet it is apparent that an increase and/or decrease in the amount of particular cytokines is correlated with certain states of disease. HIV disease causes a decrease in the function of immunity most apparent by an increase in the amount of HIV in the body and a subsequent decline in the number of T-helper/CD4 cells. As activated T-helper cells decrease in number, cytokines that are secreted by them also decline. Therefore, it appears that yet another factor related to this deficiency in immunity is the apparent absence and incapacity of particular cytokines to stimulate the further proliferation of T-cells. As immunologists have become more aware of the identities and effects of various cytokines, AIDS researchers have become more cognizant of the great significance that these chemical messengers play in natural immunity. In particular, two cytokines that have been identified as Interleukin-12 (IL-12) and Interleukin-2 (IL-2) are found to play central roles in one type of central immune reaction called the cell-mediated response. After being invaded by foreign virus or bacteria, the body's response is for particular white blood cells (notably the T-helper/CD4 cells) to prompt one of two distinct immune responses (cell-mediated response vs. humoral antibody response). However, it appears that in the case of HIV infection, balance between these two forms of immune responses becomes gradually upset. As HIV disease progression occurs, there is ultimately a decrease in the cell-mediated response and the humoral response becomes more dominant. Apparently, it is the cell-mediated immune response which appears to be most influential in the control of HIV infection. With the naturally enhancing effects that IL-12 and IL-2 present, there is an increasing interest in the potential for these cytokines to play a part in manipulating the immune system in order to treat HIV and AIDS. Apparently, there is a direct correlation between the levels of IL-12, IL-2 and cellular immunity as the activity of these cytokines stimulates the cell-mediated response. Since there is an evident decline in the production of these cytokines due to a decrease in the cell-mediated immune response, the notion of perhaps countering this suppression by treatment with a recombinant (genetically engineered) form of the lacking cytokine has become more veritable. By treating with IL-12 or IL-2, researchers are encouraged that the weakened human immune response to HIV may be empowered and gradually decrease or stop the pace of disease development. The immunomodulatory qualities of IL-12 and IL-2 have provided us with another hope for perhaps combating HIV infection and AIDS. Their natural abilities to stimulate the number of T-cells (CD4 and CD8) allow for the possibility to replete deficiencies found in the immune systems of HIV-positive persons. Present and future clinical trials involving the administration of recombinant forms of IL-12 or IL-2 examine this premise of maintaining, increasing or stimulating the cell-mediated immune response in HIV-infected individuals. IL-12 was first discovered in the late 1980's, and by 1991 it was identified by scientists at Hoffman-LaRoche and Wistar Institutes. IL-2 was also extensively studied during the 1980's, but it was first distinguished in 1976 and later cloned in 1983. Originally termed the T-cell growth factor, IL-2 has been studied to date for use in the fields of both cancer and HIV treatment for several years. IL-12 is a chemical messenger which enhances the production and activity of various cells of the immune system such as T-cells, B-cells (which in turn promote antibody production) and natural killer cells (NK cells). Activated natural killer cells are known to have the ability to destroy HIV infected T-cells. IL-2 also has the capability to stimulate NK cells, but additionally enhances the degree of " secondary " cytokines found in the body. Recombinant forms of IL-12 and IL-2 have been developed as hopeful treatments for cancer, HIV and other infectious diseases. IL-2 is currently approved by the FDA as a form of cancer treatment that physicians have already begun to use in their practice. Yet aside from past use in the management of cancer, recombinant forms of IL-12 and IL-2 are also being studied to examine their safety and efficacy in the treatment of HIV: especially when administered in conjunction with standard antiretroviral treatment. Working alongside the effects of antiretroviral therapy, the immunomodulatory enhancements of IL-12 and IL-2 may promote the efficacy of drugs such as protease inhibitors or AZT. Interleukin -2 For over ten years, IL-2 has been studied in Phase I and II AIDS clinical trials for the management of HIV infection and AIDS. The general notion that HIV disease progresses due to a caused decline in T-cells, and a subsequent reduction in the amount of IL-2, has allowed researchers to examine the possibility that perhaps the immune system can be enhanced by active administration of IL-2. In exploring the use of IL-2 as treatment for HIV and AIDS, two forms of this interleukin have been studied. The first, Proleukin, is a recombinant human form of IL-2 that was manufactured using DNA technology. The second, IL-2 fusion toxin, is formulated to transfer toxin to cells infected with HIV. However, in the attempt to find a simple solution of treating HIV through the known effects of IL-2, further investigative steps have not withheld future questions and difficulties. Looking at past AIDS clinical trials examining IL-2 treatment, there is the apparent absence of any clear-cut evidence of IL-2's benefit for treating HIV infection - partially due to developing evidence that IL-2 may also simultaneously induce more HIV. While it has been known that IL-2 stimulates the development of more T-cells, it also increases the number of those that are already infected with HIV; therefore there is a heightened concentration of HIV as cells continue to divide. In addition, IL-2 enhances the expression of secondary cytokines, one of them being Tumor Necrosis Factor Alpha (TNF-alpha) which has also been known to magnify the concentration of HIV. Therefore, with higher doses of IL-2, growth of the system of T-cells (including infected T-cells) and the number of TNF-alpha is stimulated, and subsequently an increase in the levels of HIV occurs. In light of this impeding outcome of high dose IL-2 therapy, IL-2 trials have required concomitant treatment with an antiretroviral, usually AZT. In addition, because the higher quantity of administered IL-2 apparently promotes increased HIV replication, this has caused researchers to utilize lesser amounts of IL-2 to achieve more humble goals. These more moderate objectives desired with lower IL-2 dosages include an enhancement of T-cell capacity, stimulated NK cell activity, and heightened sensitivity of IL-2 without increasing T-cell numbers. However, in light of the difficult questions which arise in the experimental study of IL-2 administration towards reestablishing a normal immune system, the occurrence of toxicities is also another limitation that presents itself in vivo. In comparison to IL-12, IL-2 is naturally released by T-cells at a later stage in the progression of the immune response. In attempts to reconstitute towards a normal immune system, researchers have discovered that dose-limiting toxicities can occur. In order to achieve relatively more heightened levels of CD4/Helper T-cells in the body, investigators observed that the higher dosage of required IL-2 also led to a range of side-effects which include flu-like indications, fever, swollen lymph nodes, and nausea to pneumonia. In addition, researchers have also realized that in order for treatment to be effectual in producing substantially increased CD4 T-cell counts, IL-2 must be administered in several doses over a longer period of time, due to the short half-life of IL-2 itself. One small trial which incorporated high doses of IL-2 administration through "intermittent continuous" infusion led to promising results for those with relatively higher CD4 cell counts at study entry. Six out of ten patients with CD4 > 200 at baseline maintained CD4 cell increases of greater than 50% when given five day infusions of IL-2 every eight weeks. Two out of 12 patients, with CD4 < 200 at study entry showed some T-cell increase from this particular scheme of drug administration. And with individuals with an entry CD4 cell count of less than 100, no enhanced immunological activity occurred. (Kovacs and Lane) Another trial, conducted by the National Insitute of Health, also brought about greater clarity to the nature of treating with IL-2 in combination with ARV therapy. In particular, it prompted the development of a scheme of dose and dose-reductions of administered IL-2 in order to have a positive balance between the apparent treatment advantages and the toxicities that may occur in the human immune system. In addition, a number of trials across the country have examined different dosages and dose schedules due to the foreseen natural fluctuation of IL-2 production in the body. These questions are being asked since the results of clinical trials involving IL-2 vary upon the frequency of administration. Overall, however, present studies of IL-2 treatment with HIV-positive patients now utilize reduced measurements of the drug compared to those dosages previously administered in the treatment of particular cancers such as kidney cancer. Another study of intermittent infusions of IL-2 with AZT and/or ddI which was presented at the 1993 International AIDS Conference in Berlin gave encouraging conclusions. From this trial, the researchers concluded that by giving a series of multiple infusions of IL-2 in combination with either AZT and/or ddI, the cooperative efforts of both elements of treatment notably heightened the number of CD4 cells and the expression of IL-2 receptors. Multiple 5-day infusions of 12-18 million IU/day of IL-2 in combination with AZT and/or ddI proved safe for HIV-positive individuals. In addition, an apparent difference in administering treatment either intravenously or by subcutaneous injection was noted. Intravenous administration allows for greatest intake of IL-2; however, this in turn leads to not only a more significant level in the number of Helper T-cells, but also a subsequent risk for increased toxicity. On the other hand, subcutaneous injection of IL-2 allows for a relatively decreased risk of hostile side effects, but with less efficacy in absorption of the drug and stimulation of T-cell levels. Yet despite these questions that have arisen from years of study on the logistics of IL-2 treatment for HIV disease, the potential theoretical benefits that IL-2 presents at this stage allows it to endure as a principal form of possible treatment in reinstating the immune system. Specifically, overall conclusions have indicated that treatment of HIV with IL-2 may be most beneficial in HIV-infected individuals whose CD4 cell counts are between 100 and 300 cells/mm3 and decreasing. However, for those with a CD4 count below 100, the evident benefits of therapy with IL-2 may not be an overall advantage against the possible toxicities that may occur. Drawing from the results of a recent Phase II study on IL-2 by Italian researchers in 1992, individuals afflicted with HIV disease and lymphoma and treated with IL-2 and AZT demonstrated improvement in their cell-mediated immunity. More noticeably, this "empowerment" of the immune system appeared to occur proportionally greater in those with higher CD4 cell counts. The combination treatment of IL-2 with AZT did not allow for further progression of HIV disease in these patients. Interleukin-12 Like IL-2, IL-12 is also a stimulating factor in the activation of certain cells of the immune system. In particular, as IL-12 incites the proliferation of T-cells, antibody-producing B-cells, and natural killer cells, this may result in yet another plausible source of treatment by which HIV may also be controlled. In fact, it appears that in comparison to IL-2, IL-12 may be less accountable for toxicities as it normally stimulates specific immune cells early in the development of the immune response. In light of this relatively lower degree of toxicity, IL-12 has become a proposed drug of great potential for enhancing immunocompromised systems. In addition, where there have been noted side effects from IL-2, adverse reactions in humans caused by IL-12 are unknown. However, in experimental lab situations, IL-12 has been shown to increase IL-2 production. This, in turn, could lead to the development of flu-like symptoms. Yet IL-12 apparently also has the capability to stay active in the body for lengthier periods of time, which makes it an even more praiseworthy option in human clinical trials. In addition, recent experiments at the National Cancer Institute on IL-12 have shown that this drug reinstated cell-mediated immunity in certain damaged cells of HIV-positive individuals, and also did not present any increase in the level of HIV as T-cell populations increased again. IL-12's ability to counteract immune dysregulation in individuals with HIV has great implications in the search for control of the disease. In June, 1994, small trials of IL-12 involving asymptomatic HIV-positive persons were instigated. These trials were attempting to examine the safety of IL-12 at different dosages and its effectiveness when administered with AZT. Theoretically, trials involving IL-12 hold great promise as there is the possibility that concomitant treatment with IL-12 and ARVs may ultimately amend the immunodeficiencies and problems brought about by HIV. The safety issue of recombinant IL-12 administration in humans is being studied under Phase I trials of HIV-positive individuals with T-cells between 100 and 500 cells/mm3. IL-12^Òs potential for therapeutic effects will be examined in future studies. In clinical trials, the recombinant human form of IL-12 (rhIL-12) is administered by injection. In 1994, the biotechnology firm, Genetics Institute, Inc., in accordance with Hoffman-LaRoche, developed rhIL-12 as possible therapy for HIV and cancer, along with other infectious diseases. Based upon in vitro demonstrations of IL-12's effects on the defense capacity of immune cells, it appeared that immunodeficiency could be countered by the addition of IL-12. In the lab, cultures of white blood cells from HIV-positive asymptomatic persons gained their capacity to fight HIV when treated with IL-12. It is hopeful that comparable effects may be achieved in humans. In addition to IL-12's stimulating effects upon such immune cells as T-cells, B-cells, and NK cells, IL-12 also has an apparent ability to activate cellular production of a natural substance in the body called interferon-gamma. Interferon-gamma is a type of biological response modifier (BRM) which is able to expand the defensive killing capability of immune cells. In other words, interferon-gamma is another mediating target upon which IL-12 places its enhancing effects in order to heighten the cell-mediated immune response. This is yet another pathway of attempting to reverse immune dysregulation and achieve a therapeutic advantage. By manipulating the impaired immune response with the treatment tools of IL-12 and/or IL-2 in conjunction with an antiretroviral, researchers are hoping to regain the natural balance between cell-mediated and humoral immune responses in order to halt HIV disease progression and reestablish a healthy immune system. HIV/AIDS researchers are investigating the potential value of accompanying antiretroviral treatment which disassembles further HIV replication, with IL-2 and/or IL-12 which reconstructs the dismembered immune system. Gaining further knowledge about the potential effects and optimum employment of these cytokines as immunomodulatory treatment for HIV is a continuing journey of questioning trials and greater understanding. There are still uncertainties which surround the logistics of IL-2 and IL-12 use in terms of dosage and frequency; however, great potential awaits for this form of treatment in the struggle against HIV disease. As advancement in the field of immunomodulatory therapy with IL-2 and IL-12 progresses, researchers are looking more strongly at the goal of manipulating the immune response and enhancing T-cell cytotoxicity against HIV. Lisa Boonprakong is a Research Study Assistant at the University of Washington, AIDS Clinical Trials Unit.

Notes From the 4th National Conference on Retroviruses and Opprtunistic Infections By Brian Coppedge

I arrived in Washington D.C. with high exceptions, remembering it was at this conference the year before that much of the good news around Protease Inhibitors had been presented. It quickly became apparent that this year's conference would not be a watershed event. Primarily, additional data was presented about ongoing trials and a few new antiretrovirals were discussed. In this article I am going to give brief reviews of some of the more interesting developments in antiretroviral therapies and discuss some the general themes covered at the conference. Starting on January 22 shortly before Dr. Ho's opening presentations, several activists and people living with AIDS (PLWA) tried to register for the conference. Organizers had limited enrollment at this year's conference turning away hundreds of doctors and PLWAs during the initial enrollment period. It was explained to the community members seeking enrollment that they would not be allowed to register, as that would not be fair to the hundreds of other people who had been denied enrollment during the official enrollment period. After lengthy discussions and negotiations it was agreed that community members would not attend the opening presentations, but if they returned in the morning they might be allowed to register for the remaining presentations. It was stressed several time by activists that they expected to be admitted the following day, and that seemed to be agreeable to the conference organizers. The following morning all of the community members seeking admission were denied entry. It seems that this conference once again forces community members and activists to address issues of access to and participation in the research process. Conference Highlights During the course of the conference several broad themes seemed to emerge. One of the most pressing questions in many peoples mind was how to prevent the development of resistance to therapies that include protease inhibitors. It seemed widely agreed that resistance occurs in two ways: failure of people to be compliant with their dosing routine, and the failure of the therapy to completely suppress viral replication. Several presenters discussed the importance of total viral suppression, stressing that if the virus is allowed to reproduce in the presence of drugs. Resistance will eventually occur. This follows the strong push for the "hit early, hit hard" theme that emerged from the Vancouver conference. Dr. Joep Lange presented a lively presentation on the future of drug trials. In his presentation Dr. Lange encouraged researchers to stop reproducing studies which have already been performed and addressed the issues of suboptimal therapy arms in trials. He stated that it is now longer acceptable to create a study that forces some participants to accept suboptimal therapy. He also chastised the pharmaceutical industry for its continued practice of only allowing their products to be tested in combinations with other drugs they manufacture. Hopefully GlaxoWellcome was listening. The most encouraging information presented revolved around various reports of the impact that the new antiretroviral therapies have had on quality of life. The City of New York released data showing a 30% decrease in the number of AIDS related deaths in 1996. In was generally agreed that introduction of the new therapies was the greatest reason for this decline. Several studies also discussed the decline in the number of illness that required hospitalization and in the duration of stay for those admitted. The obvious result of these declines was a reduction in cost to care for someone living with HIV/AIDS. Although the data was not presented at the conference, the CDC has released information supporting this decline in the death rate. Nationally there was a 13% decline in the AIDS related death rate for the first six months of 1996, but the CDC reported increases for women and people of color. The CDC data clearly points to the importance of guaranteeing access to these drugs for everyone living with HIV/AIDS. Updates on Existing Studies. In this section I want to present new data on combinations that are currently available. Many people are currently taking a combination of Saquinavir and Ritonavir, and we now have data from week 24 of this study. In the ongoing study, 71 people were randomized to arms using either 400 mg of ritonavir plus 400 mg of saquinavir, or 600 mg of ritonavir plus 600 mg of saquinavir twice daily. At 24 weeks the median viral load had seen a decrease of more than 99.9%, and CD4 increases of 114 cells. The double protease treatment suppressed the viral load to less than 200 copies for over 80% of the people in the trial. A second group of 70 people were randomized to receive the same dose, but three times a day instead of twice. After 20 weeks of treatment, median viral RNA had decreased by 99.8%, and the median CD4 had increased by 100 cells. One of the most important pieces of information reported in this study showed that the viral suppression seen at 12 weeks was very predictive of what happened at 24 weeks, which may help identify people who require more aggressive therapy. A University of Ottawa study found that the combination of saquinavir plus ritonavir may potentially help restore immune functions damaged by HIV. It analyzed 43 people who were part of another study, and determined that their blood cells had partial restoration of previously suppressed immune responsiveness. The last interesting piece on the two protease combinations involves the role the two drug therapy might play for people with advanced HIV infection who have failed other treatments. In evaluating 10 people who were treated for 1-10 months, investigators saw an increase in CD4 cells for nine of the ten people (the mean percentage increase was 275% from baseline). Five of the ten participants had viral loads that were undetectable (under 500 copies), sustained for three months or longer. During the study no opportunistic infections developed, and no adverse effects of the treatment were reported. It seems that many people are struggling to understand what role nevirapine might play in their antiretrorial therapy and some data presented might help provide some answers. The manufactures of nevirapine are stressing the importance of its ability to cross the blood brain barrier. The Institut Pasteur in Paris presented information suggesting that a decrease in plasma RNA might not coincide with a decrease of the virus in the Central Nervous System (CNS). The one person studied had very low CD4 counts (20/mm3) and a high viral load (5 log) when he began a triple combination that included Indinavir. On this therapy his CD4 count increased to 105 and his viral load in plasma was under 200 copies but his CSF viral load was 1,262,653 (6.1 log). This data adds strength to the argument that combination therapies need to include an agent with strong CNS penetration. A study conducted by Boehringer Ingelheim, the manufacturer of nevirapine showed that nevirapine was extremely effective at penetrating the blood brain barrier in vitro in both animals and in human CSF. Using an in vitro process, they were able to show that the levels of nevirapine that were detectable were twice as high as with the next closest antiretrovial (AZT). Also, information was presented to community members that suggested that nevirapine could be used in combination with protease inhibitors with certain restrictions, since nevirapine reduces the amount of saquinavir and indinavir that get absorbed into into the blood stream. It seems that any reduction in the amount of saquinavir in the plasma is risky but the reduction of Indinavir can be corrected with an increase in dosage. This article provides a brief review of only a small part of studies presented at the conference. Many new agents in development were discussed and we will continue to follow their development as significant data is presented. Brian Coppedge is the Treatment Information Specialist at STEP

Helpful STEP Fact Sheets Available!

The following Fact Sheets are available by calling our Treatment Hotline at 206-329-4857 or 1-800-869-STEP (in WA state) or dropping by our office:
Acupuncture	Early Intervention	Opportunistic Infections (OIs)	Trials (Seattle)
Acyclovir	Erythropoietin	Oral Alpha Interferon	Tuberculosis
AIDS Dementia Complex	Essiac Tea	Oral Manifestations	Vaccines
Aloe Vera	Evaluating Treatments	Ozone Therapy	Viral Load Tracker
Astragulus	Fatigue	Oral Gancyclovir	Vitamins and Minerals
AZT(Zidovudine)	Fungal Infections	PCM-4	Wasting Syndrome
AZT Resistance	Ganciclovir(Foscarnet)	Pneumocystis Carinii	Women and HIV
Bitter Melon	IL.2/IL.3	Pneumonia (PCP)
Buyers Clubs	G.I. Manifestations	Progressive Multifocal Leukoencephalopathy (PML)	In Spanish
Central Lines	Gene Therapy	Protease Inhibitors	Candidiasis
Cervical Dysplasia	Herpes	Selecting a Physician	CMV
Cimeditine (Tagamet)	Hypericin	Shark cartilage	Criptosporidiosis Y La
Colloidal Silver	Immune System	Sinusitis	Microsporidiosis
Combination Therapies	Karposi's Sarcoma	Siberian Ginseng	Heptasis A
Compund Q	Lab Test Results	Skin Manifestations	Herpes
Cryptosporidiosis	Licorice Root	STEP Purpose	MAC
CytoMegalovirus(CMV)	Long Term Survival	Steroids	Sarcoma de Kaposi (SK)
DDC (HIVID)	Marinol	T Cell Tracker	Toxo
DDI (VIBEX)	Mycobacterium Avium Complex(MAC/MAI)	3TC	Tuberculosis
Depression	Myopathy	Taxoplasmosis
D4t	NAC (N-Acetyl Cysteine)	Traditional Chinese Medicine
DXCB	Neuropathy	Treatment Strategy

Free Classes: Learn HIV Survival Strategies

HIV Health Management Series
Call STEP at 206-329-4857 to register.
Classes are from 7-9pm at the Swedish Medical Center, Seattle, Washington

May 7 Taking care of your Health Strategies for long term survival, choosing and working with a health care provider and how to understand and track your lab results.	May 28 Alternative and Naturopathic Treatments Learn about alternative treatments; herbs, vitamins and minerals that assist your immune system and where to buy them.
May 14 Understanding Antiviral Drug Options Discover where antivirals work, how to combat HIV using Conventional therapies, including new antivirals, protease inhibitors and non-nucleosides.	June 4 Nutrition Build your nutritional self defense by power packing your diet and what foods help your immune system.
May 12 Quality of Life Learn about how to manage some of side effects of HIV/AIDS by using alternative therapies such as Traditional Chinese Medicine, Acupuncture and Electrostim Therapy.	June 11 Opportunistic Infections Protect yourself against and treat opportunistic infections; new treatments that are becoming available. All classes are free. Come to as many as you like.

AIDS Survival Progress by Ken Fowler

Many people have invested millions of hours trying to find a cure for AIDS and it has been discouraging to find each step so difficult. Often the progress described in the scientific literature is masked in lingo and statistics that fail to encourage us as it should; perhaps a picture will help. Figure I is a bar chart of AIDS survival statistics for King County, Washington. It shows the percentage of those diagnosed in various years who have then survived for varying lengths of time. The presentation is not meant to be rigorous or to identify the mechanisms leading to improved survival. To create it, we counted individuals diagnosed in various years and recorded their status in subsequent years from databases maintained by the Health Department's HIV/AIDS Epidemiology Unit. In total 5089 cases are represented, although the 1983 data represent only eleven individuals. Calendar years - a somewhat gross sieve for estimating annual survival - are used. (Someone diagnosed in December and dying in January is thus counted as surviving a year - but another person diagnosed in January and dying in December of the following is also counted as surviving only one year. The count is long on some and short on others.) Discussion The figure shows that only 55% of those diagnosed in 1983 survived for a year or more while over 90% of those diagnosed ten years later now apparently do so. The number of those surviving three or more years beyond diagnosis has increased from about 10% - 60%. Perhaps most encouraging is the final jump in each series of bars. For example, 36% of those diagnosed in 1992 survived after five years compared with only 25% from the 1991 diagnosis class. These increases across the other bars are consistent with the dramatic drop in deaths in 1996 compared with previous years. This drop was 43% from 1995 for King County and was announced in February (Seattle-King County, 1997.) Similar significant drops were also announced at about the same time for New York. Protease inhibitors will hopefully prolong these trends although the recent drops in death rate had began last year before these new drugs became readily available. A number of other medical improvements over the years are significant factors leading to the results shown in Figure 1. Complicating factors in understanding AIDS survival include continually changing definitions of the disease itself. The survival literature attempts to explain some of these impacts. Lemp et al. (1990) reported a five year survival rate of only 3.4% of 4300 early San Fransisco cases and significantly improved survival especially in those diagnosed with PCP. They also found in the 1986-87 era that over 50% of those not receiving AZT as compared to ~80% of those receiving it survived beyond a year. Median survival for patients included in their study was only 12.5 months. Lafferty et al. (1991) reported similar median survival in the state of Washington but then found it to have risen to about 20 months by 1987-89. Blum et al. (1994) discussed survival in New York City after examining some 23,000 cases through mid 1989. They reported 55% for 12 months or longer and 23% survival for 36 months or longer. They suggested that the higher proportion of white MSM (men who have sex with men) cases in Western States may partly explain higher survival than was found in New York. They further tried to examine the effect of the late 1987 change in the definition of AIDS and found it to have reduced survival because only those meeting the new definition had a higher percentage of first diagnosis dementia or wasting, both of which have short survival and were not included in the prior definition. Osmond et al. (1994) studied a smaller group of San Francisco patients. They reported 55-68% survival for a year or more using the 1987 clinical diagnosis criteria but 90+% using a 200 CD4 count criterion^×with some variation but no clear trend over the years from 1983-93. For survival of three years or more they reported 7-15% using clinical criteria and 40-57% with the CD4 criterion. They concluded that the increased survival observed most likely results from PCP prophylaxis and treatment than from antiretroviral therapy. Vella et al. (1994) attempted to further examine the effect of the changing AIDS case definition considering 3500 Italian patients enrolled from 1987-91 in their study. They showed survival for a year or more to be about 73% using the earlier definition and about 88% with the later definition. Those surviving five or more years increased from approximately 25% to 50%. The new 1993 definition increased the number of AIDS cases in their population by 188%. Finally, Chaisson et al. (1995) sought survival differences among 1370 HIV+ patients treated at a single urban center, the Johns Hopkins HIV Clinic, from 1989-94. They found no survival differences due to sex, race, injection-drug use, or socio-economic status. Greater survival did result for those using PCP prophylaxis, those using AZT after enrollment (but not before), and those employed when they enrolled (thought to be in better health.) They believe that AZT use before enrollment had a negative effect on survival because of the limited duration of the efficacy of antiretroviral therapy and the fact that these patients had received the benefit before enrolling. Of the demographic variables examined, only age appeared related to survival (negatively), and they concluded that other demographic differences that have been observed in other papers are probably explained by access to adequate medical care. Of those enrolled with CD4 counts of less than 200, 70-85% survived for a year or more while 15-27% survived for three or more years. CD4 count was the most important predictor of survival in their study, as other studies have also found. For those entering the study with counts above 200, about 90-97% survived for a year or more while 75-90% survived for three or more years. All of these factors, and perhaps others not yet understood, affect the bars of the figure. Gross though it may be, it seems an interesting chart, and an optimistic view of the progress that has been made so far in the medical fight against AIDS. Ken Fowler, PhD., is a member of STEP's Scientific Review Committee References: Blum S. Tejinder PS, Gibbons J, Fordyce EJ, Lessner L, Chiasson MA, Weisfuse IB, Thomas PA. Trends in Survival among Persons with AIDS in New York City, Am J Epidemiology, 1994; 139 (4): 351-361. Chaisson RE, Keruly JC, Moore RD. Race, Sex, Drug Use, and Progression of HIV Disease, New England J of Medicine 1995; 333 (12): 751-755. Lafferty WE, Glidden D, Hopkins SG. Survival Trends of People with AIDS in Washington State, Am J Pub Health, 1991; 81 (2): 217-219. Lemp GF, Payne SF, Neal D, Temelsco T, Rutherford GW. Survival Trends for Patients with AIDS, JAMA 1990; 263: 402-406. Osmond D, Charlebois E, Lang W, Shiboski S, Moss A. Changes in AIDS Survival Time in Two San Francisco Cohorts of Homosexual Men, 1983 to 1993, JAMA 1994; 271 (14): 1083-1087. Seattle-King County Dept. of Public Health, AIDS Sentinel Newsletter, 1997; 8 (1): 1. Vella S, Chiesi A, Volpi A, Giuliano M, Florida M, Daily LG, Binkin N. Differential Survival of Patients with AIDS According to the 1987 and 1993 CDC Case Definitions, JAMA 1994; 271 (15): 1197-1199.

Clinical Trials and Studies Seeking Patients