'Long-Term Chronic Disease Management of HIV/AIDS'

Margaret Chesney, PhD, co-directs the Center for AIDS Prevention Studies at the University of California, San Francisco, where she is a professor of medicine and epidemiology. Her research focuses upon the use of behavioral and social factors in prevention and management of AIDS and other chronic conditions.

Q: How are we doing against HIV/AIDS?

A: From a global perspective, we are in serious trouble; 90 percent of the new infections occur in the developing world. In the United States, we cannot be complacent. Tens of thousands of people in the United States are infected. A subset has progressed enough to become very ill. The disease continues its all-out assault on our low-income subpopulations, particularly those who are drug users and men who have sex with other men.

Substance use comes into the picture with HIV a number of very important ways. First, we know that people are more likely to engage in risky behavior when they are under the influence of alcohol or drugs. This is true of both HIV-infected and uninfected people. HIV counselors and physicians need to be alert and either counsel patients about this risk or refer them to specialists. Second, one of the factors that emerges as a "risk factor" for non-adherence to HIV treatment regimens is alcohol and current drug use. Therefore, part of the care of HIV-infected persons needs to be discussion of substance use. These two factors can intersect for the HIV-infected person. Alcohol and substance use can lead to non-adherence, which increases the risk of the development of drug-resistant viruses, and at the same time, can lead to risky behavior. For these reasons, in the world of HIV prevention and treatment, alcohol and substance use need to be taken into account.

Q: What about all those medical breakthroughs we’ve read so much about?

A: There was a moment where we thought we were close to an answer. One magazine even ran a headline, "The Cure for AIDS." The promise has not come true. What is true is that we have more weapons to choose from. New problems emerged right along with them.[10]

Q: What are some of the new problems?

A: It used to be that when someone became infected with HIV, we had little to offer. We’d monitor them, wait for the disease to progress, and treat the complications or opportunistic infections. Hardly anyone received treatment until the disease progressed. Doctors waited until certain biological markers reached specific levels, and then they prescribed medication. There were few medications to prescribe, other than AZT (zidovudine). However, AZT has side effects, particularly fatigue. The path from infection to onset of AIDS averaged about 10 years. The process was predictable as well as inevitable.

Newer drugs have changed that. They target the fact that the virus must continually replicate itself in order to survive. At first it appeared that combinations of these drugs -- particularly the antiretrovirals and protease inhibitors -- could block the replication process. Eventually the level of live virus in the system would decline. The hope was that the decline would lead to eradication.

That hasn’t happened. This virus is cunning. The result is that the drugs work for awhile -- we can reduce the infection to the point where blood tests show no trace of it -- but eventually the virus "breaks out." It becomes resistant to the treatment and begins to replicate. When this happens, the treatment has to be changed to a new "salvage" regimen. The problem is that we don’t have an unlimited amount of treatment regimens.

Q: How does that change the patient’s situation?

A: While the individual may extend his or her life, the problem can be the quality of that life. Patients now face enormous uncertainty. Should you postpone treatment and hope for a few more years by taking daily medication and dealing with side effects? Or should you immediately attempt to kill the virus through medication? These regimens are supremely difficult to follow, and yet, once started, they require precise adherence.[6] We have no such thing as a 12-hour, timed-release capsule, as we do for headaches or colds. Antiretrovirals and protease inhibitors have a short period of effectiveness in the body. They must be reinforced every few hours. Many people take 18 pills daily. Some must be taken with food, some without. Side effects often accompany them. This situation defeats most patients, and they eventually forget or forego a cycle. The virus seizes the advantage, replicating and "breaking out" into the body. In its new form, the virus is even more of a threat than before, as now it can resist the drug to which it was exposed. Many patients are on their second or third set of salvage regimens.

Q: How can the health care system respond?

A: It can recognize HIV disease for what it is: a classic, long-term, chronic ailment that requires support from many sources to manage effectively.[4] Providers must forge real partnerships with their patients, much more than can be done in the traditional 15-minute setting with one doctor. Teams of providers must provide assistance in the areas of pharmacy, nutrition, counseling, and much more. Adequately supported by doctors, family members, partners, and friends, patients are much likelier to adhere to treatment programs. They feel better mentally, as well as physically.

Q: What are some strategies for better adherence to treatment programs?

A: I just met with a support group of women with HIV infection. They were talking about all their pills and how they hated to take them. One said she especially hated the pills because they reminded her of her disease. But another woman said she looked forward to taking them. She’d made a beautiful case for them, with plastic jewels on the sides. Pill-taking had become a comforting ritual, her time and place to do something solely for herself. That’s the kind of message that doctors must learn to convey. Not the usual medical terminology -- how many cell counts, etc. -- but a message tailored directly to these patients.

The same goes for prescriptions. Doctors and patients need to discuss all the treatment options, with the varying schedules and side effects. Together, they can select the regimen and side effects that will be the optimal match to the patient’s lifestyle. For example, if a patient is a bus driver, it would be best to not prescribe a medication that requires him or her to drink copious amounts of water each day.

Q: Collaborative approaches and psychosocial interventions often are perceived as costly and time-consuming. Why go to such effort?

A: An important answer is that it’s the humanitarian thing to do. However, there are more practical, pressing reasons in terms of reducing the spread of more virulent strains of HIV and AIDS. Patients who stick with their prescriptions can postpone costly medical problems for years, perhaps indefinitely. Though they are infected, they are able to remain active and engaged in productive meaningful lives for a longer period. At the same time, we need to recognize that as individuals with HIV/AIDS live longer, they are also more likely to resume their "normal" lives, even if it means drug use or sexual activity. If these patients have drug-resistance, the virus they transmit is more dangerous than the original one. We must prevent the development of these drug-resistant strains.

Similarly, two people who are HIV-infected may feel that engaging in unprotected sexual activity is safe because they both have the disease. However, each strain may be different, and some strains are resistant to some medications. Partners may infect each other with different strains of the disease. We need to impress upon them the importance of not engaging in these risky behaviors. Collaborative management can also teach people to care for themselves, as well as those around them.

There is a new focus in counseling HIV-infected patients about maintaining safe behavior. Physicians who see patients regularly play an important role in this counseling. They need to emphasize that the virus can be transmitted to others even when it is at very low levels in the blood. In particular, physicians should counsel patients who contract sexually transmitted diseases because this indicates that unsafe behavior is being practiced.

Interview #2:

'Adherence is Crucial'

Neil Schneiderman, PhD, is a professor of psychology, medicine, psychiatry, and biomedical engineering, at the University of Miami, Florida. He directs "Behavioral Management and Stress Responses in HIV/AIDS," a group of multidisciplinary, research projects sponsored by the National Institute of Mental Health.

Q: Why do you attach such importance to behavioral management and stress responses in HIV/AIDS patients?

A: The first AIDS cases were reported in 1981. HIV was identified as the cause in 1984. In the 16 years since, we have seen dramatic changes in the nature of treatment for this disease. New drugs introduced in 1995 were revolutionary in scope, changing everybody’s focus from palliative care to maintenance of health. Their benefits, however, depend entirely upon adherence to a complex regimen of pill-taking. In other words, behavior.

Q: But your interest in these matters goes back long before 1995.

A: That’s because of the chronic nature of this disease. There was no cure on the horizon -- still isn’t -- and so we wanted to learn how to keep people healthy as long as possible during the clinical latent period and improve their quality of life by reducing stress. In our earliest tests, we studied at-risk, gay men who wished to be tested anonymously for HIV. We found initially that the decision to enter the study was a source of stress. White blood cells and natural killer cells in both healthy and infected men were impaired. Upon learning their HIV status, however, the healthy men’s immune system returned toward normal. The infected men became more stressed and experienced further decreases in natural killer cell function. The more distress they exhibited at diagnosis, the greater the immune system decline. Two years later, this relationship continued. Psychological variables had predicted long-term immune changes and HIV progression.[16]

Q: What programs did you set up as a result of these findings?

A: We devised a cognitive-behavioral stress management approach (CBSM) to slow the course of HIV and improve quality of life. Relaxation skills training, cognitive restructuring, instruction in self-monitoring of environmental stressors, and social skills training were all part of it. It was done in a group setting so that participants could support one another. As it turned out, when infected participants were informed that they were HIV-positive, those who participated in the program experienced a buffering effect. Their physical and mental health withstood the shock much better than that of men who did not take part in the intervention. The same held true in research with men who had begun to experience disease symptoms. Most recently, we examined the effects of CBSM upon relationships among: anxiety, norepinephrine (a stress hormone), and the immune system. The buffering effect held true.[1] CBSM also helped infected men maintain normal levels of free testosterone, the absence of which leads to decreased muscle mass or wasting.[8] Relaxation exercises in group settings were associated with decreased cortisol levels and improved mood.[7]

Q: How has the development of antiretroviral medications and combination therapies changed your work?

A: As a behavioral scientist, I used to have to knock on doors to get medical doctors to give us access to their patients. Now doctors come to us and ask for help. They’ve encountered the dark side of the HIV treatment revolution. Success on a population level requires greater than 95 percent adherence to medication. When patients miss surprisingly few doses, the virus, which can produce as many as 10-to-the-tenth-power viral particles daily, overcomes the drugs. It becomes stronger and deadlier than before. In one study, 81 percent of subjects with greater than 95 percent adherence experienced complete viral suppression.[17] Of those who took medications properly from 90 to 95 percent of the time, 64 percent suppressed the virus. That result occurred in just half the people who adhered 80 to 90 percent of the time.

Q: How can we improve adherence?

A: First, it’s important to realize how much improvement is needed. Today’s HIV/AIDS patient is likely to be among our most difficult-to-reach populations. At the Miami Veterans Administration Center, we observed that few HIV patients refilled each of their prescriptions over a six-month period.[11] Most of these men were substance abusers and/or homeless. We provided special, multi-compartment pill containers, plus counseling from a doctorate-level pharmacist who explained how to fill the containers and led the men in role playing a day of their medication schedule. Compliance, measured in monthly refills for all medications, increased from 48 percent to 75 percent. Their actual adherence rate was almost certainly less. At least it was a start.

Q: So the research you conducted before the pharmaceutical revolution can be applied to current conditions?

A: Exactly. After more than 10 years of psychosocial interventions in HIV patients, we can adapt our CBSM findings to improve medication adherence and to promote safe sex practices. We target our work separately toward gay men and women. The gay community developed support groups long ago. Women, particularly African-Americans, appear to suffer more losses and psychological stressors. They tend to be poor and burdened with domestic responsibilities. Their issues differ greatly from gay men. Many women indicated that they risked physical abuse if they asked their partner to use a condom. Many face homelessness if people in their household learn of their condition. We often must support our patients without their families’ knowledge, much less assistance.

Q: Do you also have a program that specifically targets other at-risk groups such as individuals with substance abuse problems?

A: Recently, the National Institute on Drug Abuse supplemented our National Institute of Metal Health research program to allow us to conduct group-based CBSM studies in a Veterans Administration outpatient setting on HIV-infected individuals with a history of drug abuse. The intervention focuses upon medication adherence, harm reduction, and the improvement of quality of life within the context of relapse prevention and other issues pertinent to these patients. We have been attempting to integrate our intervention in relation to general primary care treatment by working with the patients’ other health care providers.

Q: What’s the next step?

A: If our behavioral studies demonstrate a clinically significant increase in medication adherence and harm-reduction across risk groups, then a large-scale multicenter trial should follow. Our studies are largely based in universities. They involve highly trained personnel and complex recruitment strategies. Eventually the studies must move into community health centers. There they will face real-world conditions.

Glossary:

The language of HIV/AIDS can be confusing. Here are some frequently used terms.[14]

AIDS (acquired immunodeficiency syndrome) -- A diagnosis that accompanies HIV infection and one or more of the following: a CD4+ cell count below 200 that occurs at least twice within six months, and/or an opportunistic infection.

Antiretroviral therapy -- Drugs that inhibit the replication of HIV or destroy it.

CD4+ cell -- Type of white blood cell that helps the body fight infections. Also known as T cell.

Combination therapy -- Multiple antiretroviral drugs taken together in order to fight HIV more effectively.

HIV (human immunodeficiency virus) -- The virus that leads to AIDS.

Protease inhibitors -- A class of antiretroviral drugs that block an HIV enzyme called protease.

Viral replication -- Process by which HIV makes more copies of itself.

Greater Need, Less Care:

Low income, minority populations have some of the highest rates of HIV infection. Nevertheless, these groups are among those least likely to receive proper care, a study of a nationally representative sample of HIV-infected people reveals.[18]

Blacks, Latinos, women, the uninsured, and Medicaid-insured all experienced less desirable patterns of care than other groups in 1996, 1997, and 1998, according to research conducted by RAND of Santa Monica, Calif., through a cooperative agreement with the Agency for Healthcare Research and Quality. Access to care improved during those years, but still the groups suffering most from HIV/AIDS received less care than white and/or privately insured patients.

Scientists conducted three interviews with each of more than 2,200 HIV-infected patients. The interviewees represented the nation’s 231,400 HIV-infected patients under care for their disease. Six indicators of quality of care were measured: receipt of any anti-retroviral therapy ever, use of protease inhibitors or non-nucleoside reverse transcriptase inhibitor AIDS drugs, use of drugs to prevent a form of pneumonia that is a major killer of HIV-weakened people, making at least two outpatient visits, not being hospitalized, and not visiting the emergency room for a problem that resulted in hospitalization.

Between 1996 and 1998, the percentage of patients in compliance with all indicators increased from 29 percent to 47 percent. The disparity between African-American and white patients in use of newly developed HIV medications decreased from 24 percent to 8 percent. The gulf between uninsured and the insured declined by half. Still, 15 percent of eligible patients had never received the new drug treatments. Members of disenfranchised groups remained less likely than others to have received these potentially life-saving medications. Gaps between male and female HIV patients remained essentially unchanged.

RAND project co-directors Martin Shapiro, MD, PhD, and Samuel Bozzette, MD, PhD, point out that any disparity in HIV treatment can be of life-or-death importance to members of the group experiencing inferior care. Treatments evolve rapidly. The challenge is to make sure the pattern of unequal access is not repeated when new drugs emerge.

Mothers With HIV Face Extra Barriers:

Mothers infected with HIV may face a large number of barriers in accessing health care and adhering to medical treatment. The majority of these women are poor, single-parent, blacks or Hispanics who eke out their lives in depressed urban areas. They are often overwhelmed by caregiving responsibilities for multiple children and family members. Many suffer from depression and anxiety disorders.[12] Substance abuse is prevalent. These risk factors all are associated with missed medical appointments and medications.

In a study of 126 mothers receiving HIV-related care at a New York City hospital, Claude Mellins, PhD, and colleagues found that 53 percent missed medication dosages in the past three months, and 20 percent missed doses within the past two days.[13] Those with psychiatric disorders were 10 times likelier than others to have missed one or more pills in the past two days, as were those who recently had abused alcohol or drugs. Nearly half had not disclosed their virus status to their children. "The results demonstrate the importance of understanding the context of mothers’ lives in predicting their access and adherence to HIV medication," says Mellins. "The integration of mental health, substance abuse, and medical services is critical to the health and well-being of HIV-infected mothers."

Steps to Collaborative Management of Chronic Conditions:

Once a chronic condition has been identified, patients do best if there is on-going commitment by patients, their families, and their health care providers to work together over time. There is strong evidence that the following simple steps taken by providers and patients can significantly improve health and well-being.

1. Define the problem jointly: Providers often define problems in terms of medical diagnoses and treatments, while patients define them in terms of the impact that symptoms have on their lives. Patients are more likely to benefit when these two perspectives are harmonized in a shared definition of the problem.

2. Develop a common action plan: Managing chronic conditions is more successful when providers and patients focus on a few specific concerns, identify realistic goals, and commit to a joint plan of action in which the responsibilities of both parties are clear.

3. Explore possible programs and services: Many chronic conditions are better managed when patients are referred by providers to special support services or behavior change programs tailored to their priorities, needs, and preferences.

4. Track progress and anticipate course corrections: Scheduled, on-going communication between providers and patients is critical to tracking progress in achieving goals, identifying potential barriers and complications, and making needed adjustments in the joint plan of action.

For more information on the Health Behavior Change in Managed Care Project, visit our Web site http://www.cfah.org

Facts of Life is prepared with assistance from:

Academy of Behavioral Medicine Research, Academy of Psychosomatic Medicine, American Academy of Nursing, Association for Applied Psychophysiology and Biofeedback, American College of Neuropsychopharmacology, American Psychiatric Association, American Psychological Association, American Psychological Association-Division 38, American Psychological Society, American Psychosomatic Society, American Sociological Association, American Society of Psychiatric Oncology, College on Problems of Drug Dependence, Institute for the Advancement of Social Work Research, International Psycho-Oncology Society, International Society for Traumatic Stress Studies, Society of Behavioral Medicine, Society for Developmental and Behavioral Pediatrics, Society for Public Health Education, Society for Research on Nicotine and Tobacco

The Research:

1. Antoni MH, Cruess DG, Cruess S, Lutgendorf S, et al. (2000). Cognitive-behavioral stress management intervention effects on anxiety, 24-hr urinary norepinephrine output, and t-cytotoxic/suppressor cells over time among symptomatic HIV-infected gay men. Journal of Consulting and Clinical Psychology, 68(1):31-45.
   
2. Bozzette S, Berry SH, Duan N, Frankel MR, et al. (1998). The care of HIV-infected adults in the United States. New England Journal of Medicine, 339(26):1897-904.
   
3. Centers for Disease Control and Prevention. (1999). HIV/AIDS Surveillance Report, 1999, 11(1):3,36.
   
4. Chesney M & Folkman S. (1999) The psychosocial management of HIV disease in adults. In Sexually Transmitted Diseases, 3rd ed., Holmes KK, Sparling PF, et al (eds.) New York: McGraw Hill. Chapter 72, pp. 987-93.
   
5. Chesney M, Folkman S & Chambers D. (1996). Coping effectiveness training for men living with HIV: Preliminary findings. International Journal of STD & AIDS, 7(Suppl. 2):75-82.
   
6. Chesney M, Ickovies J, Hecht FM, Sikipa G & Rabkin J. (1999). Adherence: A necessity for successful HIV combination therapy. AIDS, 13(Suppl A):S271-8.
   
7. Creuss DG, Antoni MH, Kumar M & Schneiderman N. (2000) Reductions in salivary cortisol are associated with mood improvement during relaxation training among HIV-seropositive men. Journal of Behavioral Medicine, 23(2):107-22.
   
8. Cruess DG, Antoni MH, Schneiderman N, Ironson G, et al. (2000). Cognitive-behavioral stress management increases free testosterone and decreases psychological distress in HIV-seropositive men. Health Psychology, 19(1):12-20.
   
9. De Rosa CJ & Marks G. (1998). Preventive counseling of HIV-positive men and self-disclosure of serostatus to sex partners: New opportunities for prevention. Health Psychology, 17(3):224-31.
   
10. Kelly JA, Otto-Salaj LL, Sikkema KJ, Pinkerton SD & Bloom FR. (1998) Implications of HIV treatment advances for behavioral research on AIDS: Protease inhibitors and new challenges in HIV secondary prevention. Health Psychology, 17(4):310-9.
    
11. Malow RM, Baker SM, Klimas N, Antoni MH, et al. (1998). Adherence to complex combination antiretroviral therapies in HIV-positive drug abusers. Psychiatric Services, 49(8):1021-2,1024.
    
12. Mellins CA, Ehrhardt AA & Grant WF. (1997). Psychiatric symptomatology and psychological functioning in HIV-infected mothers. AIDS and Behavior, 1(4):233-45.
    
13. Mellins CA, McCaskill E, Braine N, Havens J, et al. (July 1999). Factors mediating medical adherence in HIV-positive mothers. Presented in Philadelphia at the annual National Institute of Mental Health conference on the Role of Families in Preventing and Adapting to HIV/AIDS.
    
14. National Association of People with AIDS. (1999). Making Your Treatments Work for You: New Options for Simpler Regimens. Washington, DC: NAPWA.
    
15. National Institute of Allergy and Infectious Diseases. (December 1999). HIV/AIDS Statistics, NIAID Fact Sheet. Bethesda, MD. http://www.niaid.nih.gov/factsheets/aidsstat.htm.
    
16. Office of Behavioral and Social Sciences Research, National Institutes of Health, and the Social Sciences Research Council. (Volume in press, to be published 2001). Expanding the Boundaries of Health: Bio-Behavioral-Social Perspectives. Anderson N, et al (eds.) For information, contact Frank Kessel, program director, Social Sciences Research Council, (212) 377-2700.
    
17. Paterson D, Swindells S, Mohr J, Brester M, et al. (1999). How much adherence is enough? A prospective study of adherence to protease inhibitor therapy using MEMS caps. Presented at the Sixth Conference on Retroviruses and Opportunistic Infections.
    
18. Shapiro MF, Morton SC, McCaffrey DF, Senterfitt JW, et al. (1999). Variations in the care of HIV-infected adults in the United States. Journal of the American Medical Association, 281(24):2305-15.

The Center for the Advancement of Health, a nonprofit organization, promotes the science underlying the relationship between mental and physical states that influence health and illness, and works to turn that knowledge into practical health care solutions. The Center was founded by the John D. and Catherine T. MacArthur Foundation and the Nathan Cummings Foundation, which continue to provide core funding. Funding for this series was provided by the Robert Wood Johnson Foundation.

For Information Contact:
Ira R. Allen
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p. 202.387.2829 / f. 202.387-2857
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