Fatigue

Background

Fatigue is one of the most common and debilitating complaints of HIV-infected people, with an estimated prevalence of 20-69%. It is defined by Aaronson et al. as "a decreased capacity for physical and/or mental activity due to an imbalance in the availability, utilization, and/or restoration of resources needed to perform activity." The consequences of severe fatigue may include curtailment of work and other activities, need for frequent breaks, limitations in involvement with family and friends, and difficulty completing even the simplest household chores.

In HIV-infected individuals, fatigue may be caused by several comorbid conditions or by HIV itself. HIV-related fatigue is a broad term referring to fatigue that begins or significantly worsens after the patient is infected with HIV and that has no other identifiable causes. HIV-infected people with fatigue should be evaluated carefully for reversible causes, such as depression, anemia, hypogonadism, insomnia, and medication adverse effects, and should be treated aggressively if these are found. In some patients, fatigue may be related to advanced immunosuppression (with low CD4 cell counts) or to high levels of circulating HIV virus. Unfortunately, for many patients, a specific cause of fatigue is not identified. Research to date suggests that fatigue in many HIV-infected individuals may result from a complex interplay between physiologic and psychosocial variables, and studies are being conducted to define factors related to the onset or worsening of fatigue.

S: Subjective

The patient complains of tiredness, easy fatigability, a lack of energy, a need for frequent rest or naps, or waking in the morning feeling unrefreshed. The patient may report difficulty working, difficulty concentrating, inability to exercise without experiencing profound fatigue, or impairment in social relations because of fatigue.

Consider the following during the history:

• No objective clinical indicators exist for fatigue; thus, making a diagnosis of fatigue rests on subjective data.
• Fatigue assessment tools may help in diagnosing fatigue and estimating its severity. One such tool, the HIV-Related Fatigue Scale, was developed specifically for use with HIV-infected individuals (see Barroso and Lynn in "References," below); this assesses the intensity of fatigue (on the day of the assessment and during the previous week), the circumstances surrounding fatigue (including patterns), and the consequences of fatigue.
• Take a thorough history of the fatigue symptoms, including onset, duration, exacerbating and alleviating factors, and associated symptoms. Evaluate for symptoms of other conditions that cause fatigue (e.g., hypothyroidism, hypogonadism, anemia, heart failure, poor nutrition).
• Depression can cause significant fatigue and is common among HIV-infected patients with fatigue. Screen the patient for depression. A single question -- "Are you depressed?" -- has been shown to be as valid and reliable as most depression instruments. See chapter Major Depression and Other Depressive Disorders for further information.
• Inquire about social history, specifically any life stressors including those related to housing status, work stress, personal relationships, etc.
• Evaluate the patient's sleep patterns. HIV infection can interfere with sleep architecture early in the illness.
• Inquire about substance use or abuse.
• Obtain a list of all current medications, including herbal and over-the-counter preparations.
• Conduct a nutritional assessment.

O: Objective

Check vital signs and orthostatic blood pressure and heart rate measurements, if indicated. Perform a physical examination including evaluation of nutritional status, affect, conjunctivae and skin (for pallor), thyroid, lungs and heart, and deep tendon reflexes.

A: Assessment

The differential diagnosis includes the following:

• Anemia
• Hypothyroidism
• Hypogonadism
• Depression
• Insomnia or poor-quality sleep
• Substance use or abuse
• Malnutrition
• Medication adverse effects (e.g., zidovudine, interferon)
• Opportunistic infections, malignancy, chronic hepatitis B or C, mononucleosis, other illnesses
• Pregnancy

P: Plan

Diagnostic Evaluation

To rule out reversible causes of fatigue, perform laboratory tests, including:

• Hemoglobin and hematocrit
• Thyroid function tests
• Testosterone (in both men and women)
• Pregnancy test, if applicable

Fatigue assessment tools, as mentioned above, may be used to assess the intensity of fatigue, the circumstances surrounding fatigue, and the consequences of fatigue.

Treatment

If testing reveals a specific cause of fatigue, treat appropriately. For example:

• Treat anemia, hypothyroidism, or hypogonadism, as indicated.
• Treat depression with antidepressant medication, psychotherapy, or both; see chapter Major Depression and Other Depressive Disorders.
• Treat insomnia and review good sleep-hygiene practices with the patient; see chapter Insomnia.
• Refer for treatment of substance use or abuse, if possible.
• Provide counseling regarding any current life stressors that may be contributing to fatigue. Involve social work and case management services regarding housing issues or other social needs that may be contributing to fatigue.
• Treat malnutrition, ideally in conjunction with a nutritionist.
• Treat opportunistic infections and other illnesses. (See section Comorbidities, Coinfections, and Complications.)
• Control other symptoms that could be causing fatigue (e.g., diarrhea).
• If fatigue seems to be related to antiretroviral medication(s), weigh the benefits of the medication(s) against the possible adverse effects, and discuss these with the patient.

After appropriate evaluation, if the fatigue is thought to be related to HIV infection or if no specific cause is identified, consider the following:

• If HIV infection is inadequately controlled, particularly if the CD4 count is low or the HIV viral load is high, initiate or optimize antiretroviral therapy (ART), if otherwise appropriate.
• Patients taking effective ART may still experience HIV-related fatigue. Prepare patients for the possibility that fatigue may persist despite ART initiation.
• Encourage patients to track their patterns of fatigue with a fatigue diary if necessary. Once patients recognize their individual patterns, they can better cope with fatigue by planning their daily activities accordingly (e.g., performing the most strenuous tasks during times of peak energy or staggering activities to avoid excessive fatigue).
• Ask patients what seems to aggravate their fatigue. This information, too, will help patients determine their patterns of fatigue and identify self-care actions they might take to avoid triggers that will worsen the fatigue.
• Recommend moderate exercise and frequent rest.
• Refer the patient to community-based agencies for assistance with housekeeping.
• Evaluate the need for occupational therapy (e.g., energy conservation techniques) or physical therapy (e.g., reconditioning and strengthening exercises).
• Medications such as stimulants (e.g., methylphenidate, modafinil) may be helpful for some patients with severe or debilitating fatigue.

Patient Education

• Fatigue is often unrelated to the CD4 cell count or HIV viral load. Teach patients not to dismiss feelings of fatigue if they have higher CD4 counts and lower viral loads. Encourage them to discuss their symptoms with a provider.
• For patients with depression, advise them that appropriate treatment may reduce fatigue.
• Help patients identify how current life circumstances and stressors may contribute to fatigue and encourage them to seek the appropriate social services to help manage appropriately.
• Talk to patients about their sleep habits and recommend changes, as appropriate, to improve their sleep hygiene.
• Prepare patients to accept the fact that their fatigue (in some cases) may be a chronic condition, in which case it can be best managed by maintaining open communication with their provider and remaining engaged in care.

References

• Aaronson LS, Teel CS, Cassmeyer V, et al. Defining and measuring fatigue. Image J Nurs Sch. 1999;31(1):45-50.
• Barroso J. Just Worn Out: A Qualitative Study of HIV-Related Fatigue. In: Funk SG, Tornquist EM, Leeman J, et al., eds. Key Aspects of Preventing and Managing Chronic Illness. New York: Springer, 2001;183-194.
• Barroso J, Carlson JR, Meynell J. Physiological and psychological markers associated with HIV-related fatigue. Clin Nurs Res. 2003 Feb;12(1):49-68.
• Barroso J, Lynn MR. Psychometric properties of the HIV-Related Fatigue Scale. J Assoc Nurses AIDS Care. 2002 Jan-Feb;13(1):66-75.
• Barroso J, Preisser JS, Leserman J, et al. Predicting fatigue and depression in HIV-positive gay men. Psychosomatics. 2002 Jul-Aug;43(4):317-25.
• Breitbart W, McDonald MV, Rosenfeld B, et al. Fatigue in ambulatory AIDS patients. J Pain Symptom Manage. 1998 Mar;15(3):159-67.
• Chochinov HM, Wilson KG, Enns M, et al. Are you depressed?" Screening for depression in the terminally ill. Am J Psychiatry. 1997 May;154(5):674-6.
• Darko DF, Miller JC, Gallen C, et al. Sleep electroencephalogram delta-frequency amplitude, night plasma levels of tumor necrosis factor alpha, and human immunodeficiency virus infection. Proc Natl Acad Sci USA. 1995 Dec 19;92(26):12080-4.
• Duran S, Spire B, Raffi F, et al. Self-reported symptoms after initiation of a protease inhibitor in HIV-infected patients and their impact on adherence to HAART. HIV Clin Trials. 2001 Jan-Feb;2(1):38-45.
• Fontaine A, Larue F, Lassauniere JM. Physicians' recognition of the symptoms experienced by HIV patients: how reliable? J Pain Symptom Manage. 1999 Oct;18(4):263-70.
• Molassiotis A, Callaghan P, Twinn SF, et al. Correlates of quality of life in symptomatic HIV patients living in Hong Kong. AIDS Care. 2001 Jun;13(3):319-34.
• Phillips KD, Sowell RL, Rojas M, et al. Physiological and psychological correlates of fatigue in HIV disease. Biol Res Nurs. 2004 Jul;6(1):59-74.
• Sullivan PS, Dworkin MS, Adult and Adolescent Spectrum of HIV Disease Investigators. Prevalence and correlates of fatigue among persons with HIV infection. J Pain Symptom Manage. 2003 Apr;25(4):329-33.
• Vogl D, Rosenfeld B, Breitbart W, et al. Symptom prevalence, characteristics, and distress in AIDS outpatients. J Pain Symptom Manage. 1999 Oct;18(4):253-62.
• Voss JG. Predictors and correlates of fatigue in African-Americans with HIV/AIDS. Paper presented at the Association of Nurses in AIDS Care 15th Annual Conference; November 7-10, 2002; San Francisco.