Fatigue is one of the most common and debilitating complaints of HIV-infected people, with an estimated prevalence of 33-88%. Fatigue is defined by the NIH Patient Reported Outcomes Measurement Information System (PROMIS) initiative as "mild subjective feelings of tiredness to an overwhelming, debilitating, and sustained sense of exhaustion that is likely to decrease one's ability to carry out daily activities, including the ability to work effectively and to function at one's usual level in family or social roles. Fatigue is divided conceptually into the experience of fatigue (such as its frequency, duration, and intensity), and the impact of fatigue upon physical, mental and social activities." 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 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, hypothyroidism, hypogonadism, poor sleep quality, and medication adverse effects; if these are found, they should be treated aggressively. In some patients, fatigue may be related to advanced immunosuppression (e.g., low CD4 cell counts) or to high levels of circulating HIV virus. Unfortunately, for many patients, a specific cause of fatigue is not identified, and fatigue in many HIV-infected individuals may result from a complex interplay between physiologic and psychosocial variables. Recent research has examined genes that are predictive of low vs. high fatigue; abnormal neuronal circuitry involving striatal-cortical pathways that may play a role in HIV-related fatigue; prior use of didanosine or stavudine; and the presence of clinical lipodystrophy syndrome. From a psychosocial standpoint, stress, with its attendant anxiety and depression, seems to be the most consistent predictor of HIV-related 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; 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, and personal relationships.
  • 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, including 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
  • Depression
  • Hypogonadism
  • Hypothyroidism
  • Insomnia or poor-quality sleep
  • Malnutrition
  • Medication adverse effects (e.g., zidovudine, interferon)
  • Opportunistic infections, malignancy, chronic hepatitis B or C, mononucleosis, other illnesses
  • Pregnancy
  • Substance use or abuse

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
  • CD4 and HIV viral load (if not done recently), electrolytes, creatinine, and liver function tests

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


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. 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., 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 health care 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 providers and remaining engaged in care.


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