Although fever may accompany HIV infection at various stages of disease, fever in a patient with a low CD4 count (<200 cells/µL) should prompt the clinician to rule out opportunistic infections.

S: Subjective

The patient complains of persistent fever, or new-onset fever of >101°F (38.3°C).

Assess the following during the history:

  • Duration of fever
  • Associated symptoms, including chills, sweats, weight loss
  • Visual disturbances (see chapter Eye Problems)
  • Nasal or sinus symptoms
  • Asymmetric, tender, or new lymphadenopathy
  • Cough or shortness of breath (see chapter Pulmonary Symptoms)
  • Diarrhea, tenesmus (see chapter Diarrhea)
  • Rash, lesions, soft-tissue inflammation
  • Pain (for headache, see chapter Headache)
  • Neurologic symptoms (see chapter Neurologic Symptoms)
  • Vaginal or urethral discharge
  • Other localizing symptoms
  • Unprotected sexual contacts
  • Recent injection drug use
  • Intravenous line or venous access device
  • Travel within the past 6-12 months
  • Medications (as a cause of fever)
  • Use of antipyretic agents including aspirin, nonsteroidal antiinflammatory drugs (NSAIDs), and acetaminophen; when was most recent dose taken?

O: Objective

Document fever. Check other vital signs, including orthostatic measurements. Check weight and compare with previous values.

Search for evidence of an infectious focus. Perform a complete physical examination, including evaluation of the eyes (including fundus), sinuses, oropharynx, ears, lymph nodes, lungs and heart, abdomen, joints, genitals, uterus, rectum, skin, and neurologic system.

Review recent CD4 measurements, if available, to determine the patient's risk of opportunistic illnesses as a cause of fever.

A: Assessment

The differential diagnosis varies depending on the CD4 count. Possibilities include the following:

Conditions More Likely with Low CD4 Count

  • Aspergillosis
  • Cryptococcosis
  • Cytomegalovirus (CMV) infection
  • Disseminated Mycobacterium avium complex (MAC)
  • Disseminated histoplasmosis
  • HIV infection itself
  • Lymphoma, other neoplasms
  • Pneumocystis jiroveci pneumonia (PCP)
  • Toxoplasmosis
  • Tuberculosis (atypical or extrapulmonary)

Conditions That May Occur with Any CD4 Count

  • Abscess, cellulitis
  • Acute hepatitis
  • Autoimmune process
  • Bacteremia or sepsis
  • Bacterial pneumonia or bronchitis
  • Disseminated herpes simplex virus; chickenpox
  • Drug-induced fever (common culprits include abacavir, nevirapine, sulfonamides, dapsone, penicillin, clindamycin, carbamazepine, phenytoin, barbiturates, and bleomycin)
  • Endocarditis
  • Immune reconstitution syndromes, related to opportunistic infections, are often associated with fever (see chapter Immune Reconstitution Inflammatory Syndrome)
  • Influenza
  • Otitis
  • Malaria
  • Pelvic inflammatory disease (PID)
  • Sexually transmitted diseases
  • Sinusitis
  • Tuberculosis (pulmonary)
  • Urinary tract infection (UTI)

P: Plan

Diagnostic Evaluation

Perform laboratory work and other diagnostic studies as suggested by the history, physical examination, and differential diagnosis. These may include the following:

  • CD4 count (if not done recently) to help with risk stratification for opportunistic illnesses
  • Complete blood count (CBC) with differential
  • Blood cultures (bacterial, mycobacterial, fungal)
  • Urinalysis, urine culture if UTI symptoms are present
  • Liver transaminases, renal panel
  • Chest X-ray
  • Sinus films if indicated by symptoms and physical examination findings
  • If respiratory symptoms and signs are present: sputum evaluation (Gram stain and acid-fast bacilli smear, evaluation for PCP), with culture of sputum for bacterial pathogens, acid-fast bacilli, viruses, and fungi as indicated; consider sputum induction or bronchoscopy if indicated
  • Serum cryptococcal antigen, particularly if CD4 count is <100 cells/µL and symptoms are consistent with cryptococcosis
  • If neurological symptoms and signs are present: computed tomography (CT) or magnetic resonance imaging (MRI) of head, lumbar puncture
  • For new lymphadenopathy: aspirate with culture (including acid-fast bacilli and fungal) and cytology
  • For cytopenias: bone marrow aspirate and biopsy may be needed; see applicable treatment guidelines
  • For fever of unknown origin (FUO), defined as persistent fever >101°F for >3 weeks without findings on initial workup, more intensive workup may be needed, such as lumbar puncture, other scans or biopsies; consult with a specialist in infectious diseases or an HIV expert to determine whether hospitalization or other laboratory tests are needed
  • For patients who recently started abacavir or nevirapine, or other medications, rule out hypersensitivity reactions (see chapter Adverse Reactions to HIV Medications)


Once a diagnosis is made, appropriate treatment should be initiated. In seriously ill patients, presumptive treatment may be started while diagnostic tests are pending. In some cases, the source of fever cannot be identified. Consult with an HIV expert.

Symptomatic treatment may include NSAIDs (e.g., ibuprofen, naproxen), acetaminophen, and analgesics. Monitor for adverse gastrointestinal effects with NSAIDs. Cold compresses also can be used to relieve fever symptoms. Refer to a dietitian to avoid weight loss during the hypermetabolic state. See section Comorbidities, Coinfections, and Complications in this manual if an HIV-related cause is identified.

Patient Education

  • Patients should report any new fever to their health care provider. They should measure their temperature using a thermometer at home in order to report actual temperatures.
  • Patients should know that fever usually is a sign that their bodies are battling an infection. Their health care providers may need to do special tests to find out what could be causing the fever.
  • Many over-the-counter remedies are available to treat fevers. Patients should check with their 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 they can cause adverse gastrointestinal effects, especially if taken without food. Patients should let their care provider know if they need to take these medicines for more than 2 or 3 days.


  • Bartlett JG, Gallant JE, Pham PA. 2012 Medical Management of HIV Infection. Baltimore: Johns Hopkins University School of Medicine; 2012.
  • Cross KJ, Hines, JM, Gluckman SJ. Fever of Unknown Origin. In: Buckley RM, Gluckman SJ, eds. HIV Infection in Primary Care 2002. Philadelphia: WB Saunders; 2002.