Headache in HIV-infected persons may result from many causes, particularly if the CD4 cell count is low. Possible causes include infections (opportunistic and other) and central nervous system malignancies, HIV-related systemic illnesses, and medication toxicity. In addition, headache may be caused by any of the processes that cause headache in HIV-uninfected individuals. New or severe headache should be evaluated carefully.

S: Subjective

The patient complains of a new type of headache.

Determine the following during the history:

  • History of headaches or migraines
  • Characteristics of the headache (e.g., location, quality of pain, timing, duration)
  • Recent head trauma
  • Fever
  • History of sinusitis
  • Allergies
  • Visual changes
  • Dizziness, vertigo, nausea
  • Mental status changes
  • Seizures
  • Focal or other neurologic symptoms (see chapter Neurologic Symptoms)
  • New rashes or ulcerations
  • Other symptoms
  • Caffeine intake; recent changes in intake
  • New medications (e.g., zidovudine, dolutegravir)
  • Relief of headache by any medication
  • Unprotected sex, new sex partner

O: Objective

Perform a physical examination as follows:

  • Check vital signs. Look for fever, orthostasis, and hypertension.
  • Examine the head and neck for trauma, sinus tenderness, scalp or temple tenderness, and neck mobility; check lymph nodes.
  • Check the eyes, including funduscopic examination, for lesions or papilledema.
  • Look for oral lesions, dental abscess, thrush, and pharyngeal drainage.
  • Examine the lungs for abnormal sounds.
  • Check the skin, including palms and soles, for rashes or lesions.
  • Perform a complete neurologic examination, including mental status examination.
  • Review recent CD4 measurements, if available, to determine the patient's risk of opportunistic illnesses as a cause of headache.

A: Assessment

A partial differential diagnosis includes the following:

  • Anemia
  • Caffeine withdrawal
  • Central nervous system lymphoma
  • Cryptococcal meningitis
  • Cytomegalovirus (CMV) meningoencephalitis or retinitis
  • Dehydration
  • Depression, anxiety disorder
  • Fever
  • Hypertension
  • Medication adverse effect
  • Migraine or cluster headache
  • Neurosyphilis
  • Other encephalitis
  • Progressive multifocal leukoencephalopathy (PML)
  • Sinusitis
  • Stress or tension headache
  • Systemic infection
  • Temporal arteritis
  • Toxoplasmic encephalitis
  • Tuberculous meningitis; other meningitis

Other causes of headache unrelated to HIV should be considered.

P: Plan

Diagnostic Evaluation

Evaluation should include the following:

  • CD4 cell count (if not done recently), to help with risk stratification for opportunistic illnesses
  • Complete blood count with differential (if fever or suspected anemia); see chapter Fever
  • Blood chemistries, including liver function tests, electrolytes, creatinine, glucose
  • Serum cryptococcal antigen (if fever is present and CD4 count is <100 cells/µL); see chapter Cryptococcal Disease
  • Toxoplasma immunoglobulin G (consider if previously negative and CD4 count is <100 cells/µL; may indicate risk of toxoplasmosis); see chapter Toxoplasmosis
  • Syphilis testing: rapid plasma reagin (RPR) or Venereal Disease Research Laboratory (VDRL) test; see chapter Syphilis

When indicated, also consider:

  • Computed tomography (CT) scan with contrast or magnetic resonance imaging of the head; see chapter Neurologic Symptoms
  • Lumbar puncture with cerebrospinal fluid (CSF) studies to include opening pressure, cell count, chemistries, bacterial cultures; fungal and acid-fast bacilli evaluations and cultures; India ink stain; cryptococcal antigen, VDRL, as indicated
  • Sinus imaging
  • Erythrocyte sedimentation rate, if temporal arteritis is suspected


  • Once a diagnosis is made, appropriate treatment should be initiated. In seriously ill patients, presumptive treatment may be initiated while diagnostic test results are pending. In some cases, the source of headache cannot be identified. Consult with an HIV expert or a neurologist.
  • Refer to disease-specific treatment guidelines or primary care management guidelines as appropriate.
  • Treat symptomatically with nonsteroidal antiinflammatory drugs (NSAIDs), acetaminophen, or narcotics, if indicated, to control pain.

Patient Education

  • Headache can be a sign of an opportunistic infection, especially in patients with low CD4 cell counts. Patients should notify their health care provider if they develop a new headache.
  • Providers should inform patients that they may have to do additional tests to determine the cause of the headache.
  • Many over-the-counter remedies are available for headache. Patients should check with their health care provider before taking these. Acetaminophen-containing products (e.g., Tylenol) generally are well tolerated. Persons with liver disease should use acetaminophen only as prescribed. NSAIDs (e.g., ibuprofen, naproxen) may be used, but these agents can cause adverse gastrointestinal effects, especially if taken without food. Patients should inform their care provider if they need to take these medicines for more than 2 or 3 days.


  • McGuire D. Neurologic Manifestations of HIV. In: Coffey S, Volberding PA, eds. HIV InSite Knowledge Base [textbook online]; San Francisco: UCSF Center for HIV Information; June 2003. Accessed December 1, 2013.