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STEP Perspective


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 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.


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&QUOT; 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
  2. Diminished interest or pleasure in all or most activities.
  3. Increased or decreased sleep nearly every day.
  4. Fatigue or loss of energy nearly every day.
  5. Loss of appetite or weight.
  6. Insomnia or increased sleep.
  7. Feelings of worthlessness or excessive or inappropriate guilt.
  8. Decreased ability to concentrate.
  9. Agitation.
  10. Recurrent thoughts of death, suicidal thoughts or suicide attempt.
  11. 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
Headache, fever, depression
HIV Associated Dementia Memory loss, social withdrawal, personality change
Lymphoma, PML Withdrawal, depression, focal neurologic changes

Treatment Options


Combination Therapy

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
  1. Rule out causes of medical illness that may present as depressive symptoms
  2. Review all currently prescribed medications. Evaluate for any possible drug-drug interactions
  3. Address issues of alcohol and substance abuse/dependence
  4. Consider how the individual currently tolerates medications (e.g. sensitivity to side effects)
  5. 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)
  6. The presence of depression and weight loss may indicate use of mirtazapine (Remeron) which both stimulates appetite and increases weight
  7. The presence of depression and neuropathy may indicate the use of TCAs, as these may augment neuropathic symptoms
  8. In advanced HIV infection, as in other chronic illnesses, stimulants may improve mood, energy, an alertness and cognitive ability
  9. Additionally, for those people with low testosterone levels, testosterone replacement may improve depressive symptoms
  10. Educate the client about the course of depression, treatment response and side effects
  11. 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

  1. Markowitz JC, Klerman GL, et al.: Individual psychotherapies for depressed HIV-positive patients. Am J Psychiatry. 1995; 152:1504-1509.
  2. 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.
  3. 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.
  4. Vitello B, Stover ES: Psychopharmacology in HIV-positive patients: research perspective. Psychopharmacol Bull 1996; 32:293-297.
  5. Markowitz JC, Rabkin JG, Perry SW: Treating depression in HIV-positive patients. AIDS 1994; 8:403-412.
  6. 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.


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.


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.


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.


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.

2 eggs/1 slice of toast with butter/herb tea or juice
cheese and crackers/1 cup juice
2 cup juice/pop/Peanut butter and jelly sandwich/4 Fig Bars
Candy bar/2 cups juice
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.


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.


Immune Modulation Therapy with IL-2 and IL-12

by Lisa Boonprakong





Interleukin -2












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:

AcupunctureEarly InterventionOpportunistic Infections (OIs)Trials (Seattle)
AcyclovirErythropoietinOral Alpha InterferonTuberculosis
AIDS Dementia ComplexEssiac TeaOral ManifestationsVaccines
Aloe VeraEvaluating TreatmentsOzone TherapyViral Load Tracker
AstragulusFatigueOral GancyclovirVitamins and Minerals
AZT(Zidovudine)Fungal InfectionsPCM-4Wasting Syndrome
AZT ResistanceGanciclovir(Foscarnet)Pneumocystis CariniiWomen and HIV
Bitter MelonIL.2/IL.3Pneumonia (PCP)
Buyers ClubsG.I. ManifestationsProgressive Multifocal Leukoencephalopathy (PML)In Spanish
Central LinesGene TherapyProtease Inhibitors Candidiasis
Cervical DysplasiaHerpesSelecting a Physician CMV
Cimeditine (Tagamet)HypericinShark cartilage Criptosporidiosis Y La
Colloidal SilverImmune SystemSinusitis Microsporidiosis
Combination TherapiesKarposi's SarcomaSiberian GinsengHeptasis A
Compund QLab Test ResultsSkin Manifestations Herpes
CryptosporidiosisLicorice RootSTEP Purpose MAC
CytoMegalovirus(CMV)Long Term Survival Steroids Sarcoma de Kaposi (SK)
DDC (HIVID)MarinolT Cell Tracker Toxo
DDI (VIBEX)Mycobacterium Avium Complex(MAC/MAI)3TC Tuberculosis
D4tNAC (N-Acetyl Cysteine)Traditional Chinese Medicine
DXCBNeuropathyTreatment 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
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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.)


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


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

The HIV Research Division at Swedish
Medical Center

Open enrollment for the following trials:
  • Amphotericin B/gm-csf - A10 week study of treatment for fluconazole-resistant oral thrush.
  • Amphotericin B/Ambisome - A 10 week study of treatment for cryptococcal meningitis.
New studies will open periodically.
Call Janice Price, R.N. for information
(206) 386-2523

University of Washington AIDS Clinical Trials Unit

1001 Broadway, Suite 218, Seattle, WA 98122-4304
List of Studies - Spring 1997

Patients are being sought for the following studies. Screening tests, study medications, and laboratory and clinical monitoring that are performed as a part of our studies are free of charge for potential participants. The adult unit does not assume the role of primary care provider for study participants, but coordinates with each patient's primary care provider. Physicians or potential enrollees can call Karen Novak or Andrea York at 206-731-3184 for additional information or appointments.

Study Drug
or Topic
Study Overview

Antiretroviral/Immunological Studies:
CD4>=200/mm3 Long-term Treatment Strategies (Study #343) A randomized double-blind trial of three "maintenance" regimens for HIV infected patients receiving 6 mos "induction" therapy with AZT, 3TC, and indianavir who have HIV RNA that becomes "undetectable&quo t;: a small subset may stop therapy at 18-36 months. Frequent real time HIV RNA after 6 mos. Three substudies (immunology, virology, pharmocokinetics.
Starting Nucleoside Antiretroviral Therapy Hearing Loss with AZT or ddI (Study #047) Patients starting zidovudine (AZT) and/or didanosine (ddI) will have a hearing test before starting therapy, and at 16 and 32 weeks after starting therapy. Patients receive $20 compensation for each hearing test.
CD4 200-700/mm3 Use of Hydroxyurea (Study #307) A 24 week comparative study of 2 doses of hydroxyurea (HU) alone vs. ddI alone or in combination, followed by combination therapy (HU/ddI).
CD4 200-500/mm3 Delavirdine (Study #021) A 24 month randomized, double-blind study of delavirdine in combination with AZT and 3TC vs. delavirdine and AZT vs. AZT and 3TC. Patients must have had< 6 months prior AZT and no previous d4T, ddI, ddC, or 3TC.
CD4 200-500/mm3 Merck Protease Inhibitor (Study #054) A 36 week study comparing a triple regimen of zidovudine (ZDV), lamivudine (3TC) and indianavir, comparing the IDV taken twice a day vs. three times a day. Requires 16 weeks prior ZDV and no prior 3TC.
CD4 -50/mm3
(part 1)
Interleukin 12 (IL-12) (Study #325) A 4 week study of Interleukin 12 (IL-12) vs. Placebo (3/4 of patients will receive IL-12). Patients must be on at least two antiretroviral drugs and must stay on those during the study. Patients with CMV or MAC or not eligible. Patients will receive $200 compensation for the study.

Study Drug
or Topic
Study Overview
Opportunistic Infections:
Oropharyngeal Candidiasis
Fluconazole (Study #323) Open-label study of fluconazole in two long-term management strategies comparing chronic suppressive therapy versus episodic therapy for oropharyngeal candidiasis. For patients with CD4 - 150; to be followed for 24 months.
Cryptosporidiosis Nitazoxanide (Study #336) Nitazoxanide vs. placebo for 21 days, followed by open-label nitazoxanide for 20 days for patients with cryptosporidiosis. Responders will be offered maintenance therapy for up to 24 weeks.
Flucanazole Resistant
Oral Amphotericin Suspension (Study #295) A 2-4 week open-label study of amphotericin suspension for thrush refractory to high-dose flucanozole. Six-month maintenance phase available to patients who respond.
MAC Treatment
Clarithromycin + Ethambutol and/or Rifabutin (Study #223) A 48 week, randomized, open-label study comparing efficacy of 3 clarithromycin containing drug regimens for disseminated MAC disease.

Other Conditions:
Drug Interactions in CD 4+ >200/mm3 TMP/SMX,
(in various combinations)
(Study #283)
An 8-week, open-label study of varying combinations of medications commonly used in late HIV, to study their interactions. Excludes patients who clinically need study Rxs. Patients receive $400 in reimbursement.
Painful Peripheral Neuropathy Recombinant Human Nerve Growth Factor (Study #291) A 23 week, randomized, double-blind study of Human Nerve Growth Factor vs. Placebo for treatment of painful peripheral neuropathy. NGF is given by subcutaneous injection twice a week.
Cervical Dysplasia 5-FU A 6 month, open-label study comparing bi-weekly applications of 5-FU cream with observation alone, following standard treatment. Pregnant women will be excluded. Contact Dr. Heather Watts at 543-5555 or Connie McLellan RN, MN at 731-3476.
1st RBC Transfusion in HIV Filtered vs. routine RBCs Prospective randomized study of filtered vs. routinely prepared RBC in persons with HIV getting their first clinically indicated RBC transfusion. Contact Dee Townsend-McCall at 680-2612 (pager) or Dr. Ann Collier at 731-3293.
Known or Suspected Kaposi's Sarcoma HHV-8 Study of newly discovered virus (HHV-8) which may cause Kaposi's Sarcoma. Study includes 1 visit for history, physical and specimen collection and is conducted at the UV Viral Disease Clinic. Skin biopsy requested but not mandatory. Compensation up to $72. Call Peter Tretheway, PA, at 720-4340.

Study Drug
or Topic
Study Overview

Natural History Studies:
HIV < 6 months Acute Primary HIV Prospective, longitudinal studies about acute HIV infection (documented to be <6 months in duration). Issues being addressed include natural history of HIV infection (virulence, site of infection, route of infection) and relationship of time of infection to viral isolation in CSF and GU tract. Contact Theresa Shea, PA-C, at 667-5300.

ACTU Web Page: http://weber.u.washington.edu/~actu

ACTU Email:actu@u.washinton.edu

