Causes

• Persistent generalized lymphadenopathy: This is often the earliest symptom of HIV infection after primary infection. Because of marked follicular hyperplasia in response to HIV infection, the lymph nodes have very high viral concentrations. Persistent generalized lymphadenopathy may be observed at any point in the spectrum of immune dysfunction and is not associated with an increased likelihood of developing AIDS.
• Oral lesions
  • Thrush: This can result from Candida infection and oral hairy leukoplakia, presumably due to Epstein-Barr virus (EBV) infection. It is usually indicative of fairly advanced immunologic decline, generally occurring in patients with CD4 cell counts of 200-500/µL.
  • HSV lesions: The finding of HSV lesions can also reflect deteriorating immune function in patients infected with HIV.
  • Reactivation of herpes zoster (shingles): Observed in 10-20% of patients infected with HIV infection, shingles indicate a modest decline in immune function and are often the first clinical indication of immunodeficiency.
  • Aphthous ulcers of the posterior oropharynx: These affect 10-20% of patients infected with HIV. Their etiology is unknown. These ulcers can be very painful and can cause dysphagia if left untreated.
• Hematologic
  • Anemia
    • All other causes of anemia should be excluded systematically before concluding that anemia is due to HIV infection.
    • With disease progression, patients infected with HIV develop a moderate-to-severe hypoproliferative anemia. The most common form of anemia observed in patients infected with HIV has the characteristics of anemia of chronic disease.
    • Anemia may be a complication of opportunistic infections and/or it may be due to marrow damage from the virus or from drug toxicity (eg, zidovudine, also known as azidothymidine [AZT]).
  • Thrombocytopenia
    • Thrombocytopenia may also be an early consequence of HIV infection. Approximately 3% of patients infected with HIV with CD4 cell counts greater than 400/µL have platelet counts of less than 150,000/µL. Of patients who have CD4 cell counts less than 400/µL, 10% also have platelet counts of less than 150,000/µL.
    • HIV-associated thrombocytopenia is rarely a serious clinical problem. In most cases, platelet counts remain greater than 50,000/µL and the condition can be treated conservatively.
    • Idiopathic thrombocytopenia observed in patients with HIV infection is very similar to the thrombocytopenia observed in patients with idiopathic thrombocytopenic purpura (ITP). Immune complexes containing anti-gp 120 antibodies and anti–anti-gp 120 antibodies have been found in the circulation and on the surface of platelets. Because these data point to an immunologic basis for the thrombocytopenia observed in patients infected with HIV, most of the treatments used are immune-based.
    • Another mechanism for HIV-induced thrombocytopenia is a direct effect of HIV on megakaryocytes, evidenced by a defect and subsequent decrease in platelet production.
    • In patients infected with HIV, thrombocytopenia has also been reported as a consequence of classic thrombotic thrombocytopenic purpura (TTP). This clinical syndrome, consisting of fever, thrombocytopenia, hemolytic anemia, and neurologic and renal dysfunction, is a rare complication of early HIV infection.
• Neurologic
  • Aseptic meningitis: This can be observed in all but the very late stages of HIV infection. This suggests that aseptic meningitis in the setting of HIV infection is an immune-mediated disease. Aseptic meningitis due to HIV infection usually resolves spontaneously within 2-4 weeks. Signs and symptoms may persist long-term in some patients.
  • Acute inflammatory demyelinating polyneuropathy: Through unknown mechanisms, HIV infection can mimic Guillain-Barré syndrome.
  • Mononeuritis multiplex: A necrotizing arteritis of peripheral nerves, this condition is another autoimmune peripheral neuropathy observed in patients infected with HIV.
  • Myopathy: AZT can cause myopathy; this is often reversible once the drug is discontinued. HIV infection can also cause myopathy by direct damage to the muscle cells. The exact mechanism has not yet been elucidated.