AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

The clinical effects of infection with human immunodeficiency virus (HIV) are diverse, ranging from an acute syndrome associated with primary infection to a prolonged asymptomatic state to advanced disease. Experts regard HIV disease as beginning at the time of primary infection and progressing through numerous stages. For most patients, active virus replication and progressive immunologic impairment occur throughout the course of HIV infection, even during the clinically latent stage. HIV disease can be divided empirically based on the degree of immunodeficiency into (1) early stage (ie, CD4 T-cell count >500/µL), (2) intermediate stage (ie, CD4 cell count 200-500/µL), and (3) advanced stage (ie, CD4 cell count <200/µL).

The stage of HIV infection when CD4 cell counts are greater than 200/µL has been given a variety of names, including pre–acquired immune deficiency syndrome (AIDS) and AIDS-related complex. Note that these 2 terms are being used less frequently.

The time from initial infection to clinical disease is highly variable, with a median time of approximately 10 years. HIV disease with active virus replication usually progresses during this asymptomatic period, and the rate of disease progression correlates directly with HIV RNA levels. Patients with high levels of HIV RNA progress to symptomatic disease faster than patients with low levels of HIV RNA.

In many patients, opportunistic diseases may be the first manifestations of HIV infection. Some patients who are otherwise asymptomatic develop persistent generalized lymphadenopathy (PGL) during this time. With few exceptions, CD4 cell counts decline progressively during this asymptomatic period at an average rate of approximately 50/µL/y. Patients with early symptomatic HIV infection have CD4 cell counts greater than 200/µL. When the CD4 cell count falls to less than approximately 200/µL, the resulting state of immunodeficiency places patients at high risk for opportunistic infections and neoplasms, thus, clinically apparent disease.

Many of the initial problems encountered while CD4 cell counts remain greater than 200/µL are not sufficiently indicative of a defect in cell-mediated immunity to be considered AIDS-defining illnesses. Some of these problems appear to be direct effects of long-standing HIV infection. Equally important is the fact that the clinical findings at the stage of disease encompassed by early symptomatic HIV infection, while indicative of a decline in immune function, are generally less predictive of overall patient status than the data obtained from serial measurements of CD4 cell counts.

Pathophysiology

Acute HIV infection affects the lymphatic system, skin, gastrointestinal system, genitourinary system, bone marrow, and neurologic system. Clinical findings observed in acute HIV infection include the following:

• Lymphatics - Persistent generalized lymphadenopathy
• Oral lesions
• • Thrush
  • Oral hairy leukoplakia
  • Pharyngitis
  • Herpes simplex virus
  • Reactivation herpes zoster (shingles)
• Dermatologic - Rash
• Hematologic
• • Anemia
  • Thrombocytopenia
• Neurologic
• • Primary (ie, due to HIV infection)
  • Secondary due to opportunistic infections: These usually occur when CD4 cell counts are less than 200/µL.
  • • Toxoplasmosis
    • Cryptococcosis
    • Cytomegalovirus infection
    • Mycobacterium tuberculosis infection
    • Syphilis
    • Human T-cell leukemia virus type I infection
  • Secondary due to neoplasms: These usually occur when CD4 cell counts are less than 200/µL.
  • • Progressive multifocal leukoencephalopathy
    • Primary CNS lymphoma
  • Secondary due to other causes
  • • Aseptic meningitis
    • Peripheral neuropathies (eg, mononeuritis multiplex, Guillain-Barré–like syndrome)
    • Myopathy

Mortality/Morbidity

Acute HIV infection comprises a range of diseases. Morbidity varies depending on the condition. By definition, no mortality is associated with acute HIV infection.

Race

No racial predilection is documented for patients with acute HIV infection.

Sex

Both sexes are affected with the constellation of symptoms that define the syndrome of acute HIV infection.

Age

This condition can affect patients of any age.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

The clinical manifestations observed for acute HIV infection are numerous, and multiple systems can be affected. The discussion below outlines the historical course and physical findings of the conditions observed in acute HIV infection. Oral lesions, including thrush, hairy leukoplakia, and aphthous ulcers, are particularly common during this stage of HIV infection.

• Persistent generalized lymphadenopathy: Patients have a history of enlarged lymph nodes (>1 cm) involving 2 or more extrainguinal sites for more than 3 months without an obvious cause.
• Oral lesions
• • Thrush may be present.
  • Patients may have oral hairy leukoplakia.
  • Herpes simplex virus (HSV) lesions may be present and can be painful.
  • Reactivation of herpes zoster (shingles) occurs in patients infected with HIV, with a relapse rate of approximately 20%.
  • Aphthous ulcers are shallow and painful and typically affect the posterior oropharynx.
• Hematologic
• • Anemia may be present, and patients usually present with fatigue and malaise.
  • Thrombocytopenia may also be an early consequence of HIV infection, but typically it is not symptomatic. Bleeding of the gums, extremity petechiae, and easy bruising are common presenting features in patients with clinically significant thrombocytopenia.
• Neurologic manifestations: These result in significant morbidity for patients infected with HIV.
• • These manifestations may be either primary (ie, due to HIV infection) or secondary (ie, due to opportunistic infections, neoplasms, or other conditions [peripheral]).
  • Opportunistic infections and neoplasms include toxoplasmosis, cryptococcosis, cytomegalovirus (CMV) infection, human T-cell leukemia virus type I infection, M tuberculosis infection, syphilis, progressive multifocal leukoencephalopathy, and primary CNS lymphoma. Secondary processes typically occur when CD4 cell counts are less than 200/µL.
  • Neurologic conditions that can occur during the acute HIV infection phase include aseptic meningitis, peripheral neuropathies (eg, mononeuritis multiplex, Guillain-Barré–like syndrome), and myopathy.
  • Aseptic meningitis can be observed in all but the very late stages of HIV infection. Patients may experience headache, photophobia, and frank encephalitis. Aseptic meningitis due to HIV infection usually resolves spontaneously within 2-4 weeks. Signs and symptoms may persist long-term in some patients.
  • Peripheral neuropathies are common in patients infected with HIV. They occur at all stages of illness and take various forms, as follows:
  • • Acute inflammatory demyelinating polyneuropathy: Patients commonly present with progressive weakness, areflexia, and minimal sensory changes.
    • Mononeuritis multiplex: This is a necrotizing arteritis of peripheral nerves. Patients develop multifocal asymmetric cranial or peripheral nerve lesions, including facial or laryngeal palsy, wristdrop or footdrop, and other neuropathic symptoms.
    • Myopathy: This may range in severity from an asymptomatic creatine kinase elevation to a subacute syndrome characterized by proximal muscle weakness and myalgia.

Physical

• Persistent generalized lymphadenopathy: During the examination, the nodes are generally discrete and freely mobile.
• Oral lesions
• • Thrush manifests as a white exudate, often with an erythematous mucosa. Thrush is observed most commonly on the soft palate. Early lesions can also be found along the gingival border. The diagnosis is made by direct examination of a scraping for pseudohyphal elements, which are characteristic of Candida species (typically Candida albicans). Severe cases can involve the esophagus, with resultant dysphagia or odynophagia.
  • Oral hairy leukoplakia manifests as filamentous white lesions, generally along the lateral borders of the tongue.
  • HSV causes lesions. Oral and genital lesions are most common, but perianal and periungual lesions are also observed. Herpetic lesions resemble a cluster of vesicles on an erythematous base.
  • Reactivation of herpes zoster (shingles) is characterized by varicella-zoster virus (VZV) lesions that may extend over several dermatomes. Widespread cutaneous dissemination may occur, but visceral involvement has not been reported.
  • Aphthous ulcers are shallow and painful and usually affect the posterior oropharynx.
• Hematologic
• • Anemia may be present, and the physical examination may reveal pallor.
  • For thrombocytopenia, as in other forms of thrombocytopenia, bleeding is rare, unless the platelet count falls to less than 10,000/µL. If this occurs, bleeding gums, extremity petechiae, and easy bruising are common presenting features.
• Neurologic
• • With aseptic meningitis, patients may experience headache, photophobia, and frank encephalitis. Cranial nerve involvement may be observed. Cranial nerve VII is affected predominantly; sometimes, nerves V and/or VIII are also affected.
  • Acute inflammatory demyelinating polyneuropathy findings include weakness, areflexia, and minimal sensory changes.
  • With mononeuritis multiplex, patients develop multifocal asymmetric cranial or peripheral nerve lesions, including facial or laryngeal palsy, wristdrop or footdrop, and other neuropathic symptoms. Early in the course of HIV infection, mononeuritis multiplex is usually limited to a single nerve or a few nerves and resolves spontaneously without treatment.
  • Myopathy is characterized by proximal muscle weakness as the primary clinical finding.

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.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Persistent generalized lymphadenopathy

CD4⁺ cell counts greater than 200/µL - Adenopathic form of Kaposi sarcoma (KS)

CD4⁺ cell counts less than 200/µL - Adenopathic form of KS, lymphoma, mycobacterial infection, toxoplasmosis, systemic fungal infection, bacillary angiomatosis

Oral lesions

CD4⁺ cell counts greater than 200/µL - Thrush, hairy leukoplakia, aphthous ulcers, herpes simplex, herpes zoster

CD4⁺ cell counts less than 200/µL - Thrush, hairy leukoplakia, aphthous ulcers, herpes simplex, herpes zoster, CMV infection, KS

Miscellaneous

All other causes of anemia

All other causes of thrombocytopenia

All other causes of meningitis

Acute inflammatory demyelinating polyneuropathy

Guillain-Barré syndrome

Lambert-Eaton syndrome

Botulism

Myasthenia gravis

Mononeuritis multiplex

Diabetes mellitus

Vitamin B-12 deficiency

Adverse effects from metronidazole (Flagyl) or dapsone

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• The workup varies depending on the condition. For additional details, refer to the articles on the conditions that comprise early symptomatic HIV infection, links to which are provided below and in Medication.
• Persistent generalized lymphadenopathy: A clinical diagnosis using lymph node biopsy is not indicated in patients with early-stage HIV disease unless the patient has signs and symptoms of systemic illness (eg, fever, weight loss) or if lymph nodes begin to enlarge, become fixed, or coalesce.
• Thrush: Diagnosis is made by direct examination of a scraping for pseudohyphal elements. Culturing is of no value because most patients with HIV infection have a throat culture result positive for Candida even in the absence of thrush.
• Oral hairy leukoplakia: Typically, the diagnosis is clinical. Biopsy tissue findings reveal epithelial hyperplasia with protruding hairs and minimal inflammation. EBV can be visualized with electron microscopy, immunofluorescence, or Southern blot analysis. See Hairy Leukoplakia for more details.
• Aphthous ulcers: These are diagnosed clinically. Examination of biopsy tissue reveals nonspecific inflammation and is not diagnostic. The primary role for a biopsy is in cases in which distinguishing between aphthous ulcers and HSV lesions is difficult.
• Herpes simplex virus: Viral culture is the criterion standard for diagnosis. Viral polymerase chain reaction of intralesional fluid is also a highly sensitive marker. Results from a Tzanck preparation (ie, Giemsa stain of vesicle contents) reveal multinucleated giant cells and intranuclear inclusions specific for HSV or VZV, but the sensitivity is low. See Herpes Simplex for more details
• Varicella-zoster virus: Viral culture is the criterion standard for diagnosis. Results from a Tzanck preparation (ie, Giemsa stain of vesicle contents) reveal multinucleated giant cells and intranuclear inclusions specific for HSV or VZV, but the sensitivity is low. See Herpes Zoster for more details.
• Anemia: A thorough evaluation is essential to exclude all other causes of anemia, especially any correctable causes. In addition to the workup detailed in Anemia, measuring the serum erythropoietin (EPO) level can help distinguish between bone marrow damage (ie, normal EPO level) and inflammatory anemia (ie, low EPO level).
• Thrombocytopenia: A thorough evaluation is essential to exclude all other causes of thrombocytopenia (eg, see Thrombotic Thrombocytopenic Purpura), such as drug toxicity, lymphoma, fungal infection, and mycobacterial infection. Bone marrow examination generally reveals a normal or increased number of megakaryocytes.
• Neurologic: A lumbar puncture is an important element of the evaluation of patients infected with HIV with neurologic abnormalities. A lumbar puncture is most helpful in the diagnosis of opportunistic infections.
• • Aseptic meningitis: Cerebrospinal fluid examination reveals lymphocytic pleocytosis, an elevated protein level, and a normal glucose level.
  • Acute inflammatory demyelinating polyneuropathy: Cerebrospinal fluid examination reveals a pleocytosis and increased protein. A peripheral nerve biopsy reveals findings of a perivascular infiltrate suggesting an autoimmune etiology. Electromyography (EMG) findings reveal demyelination.
  • Myopathy: Serial creatine kinase levels are useful to follow the course of HIV myopathy. EMG is a sensitive diagnostic test in patients with HIV myopathy. The most common finding after muscle biopsy is scattered myofiber degeneration with occasional inflammatory infiltrates. Other pathological findings include nemaline rod bodies, cytoplasmic bodies, and mitochondrial abnormalities.

Other Tests

• Electromyography
• • Findings are demyelination in acute inflammatory demyelinating polyneuropathy.
  • EMG is also useful for evaluating mononeuritis multiplex; results generally reveal multifocal axonal neuropathy.
  • EMG is a sensitive test for the evaluation of HIV myopathy.

Procedures

• Acute inflammatory demyelinating polyneuropathy - Peripheral nerve biopsy
• Mononeuritis multiplex - Nerve biopsy
• Myopathy - Muscle biopsy

Histologic Findings

• Thrush: Microscopic examination of a scraping of the lesion shows pseudohyphal elements.
• Oral hairy leukoplakia: Biopsy tissue reveals epithelial hyperplasia with protruding hairs and minimal inflammation. EBV can be visualized with electron microscopy, immunofluorescence, or Southern blot analysis.
• HSV and VZV: Results from a Tzanck preparation (ie, Giemsa stain of vesicle contents) reveal multinucleated giant cells and intranuclear inclusions specific for HSV or VZV.
• Thrombocytopenia: Bone marrow examination generally reveals a normal or increased number of megakaryocytes.
• Acute inflammatory demyelinating polyneuropathy: Peripheral nerve biopsy reveals findings of a perivascular infiltrate suggestive of an autoimmune etiology.
• Mononeuritis multiplex: Biopsy of nerve tissue reveals inflammation and vasculitis. In some cases, CMV inclusions have been found.
• Myopathy: The most common finding after muscle biopsy is scattered myofiber degeneration with occasional inflammatory infiltrates. Other pathological findings include nemaline rod bodies, cytoplasmic bodies, and mitochondrial abnormalities.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

Detailed discussion of the treatments for all of the conditions listed is extremely complicated and is beyond the scope of this review. See other articles for detailed treatment discussions for the above-mentioned conditions that comprise early symptomatic HIV infection.

For example, see Herpes Simplex, Herpes Zoster, Hairy Leukoplakia, Anemia, Toxoplasmosis, Cytomegalovirus, Cryptococcosis, Tuberculosis, Syphilis, and Candidiasis. An overview is provided in this section and in Medication.

• Candidiasis (usually oropharyngeal; esophageal candidiasis is typically characterized by a CD4 cell count <200/µL)
• • Fluconazole
  • Itraconazole
  • Clotrimazole troches
  • Nystatin suspension
  • Amphotericin B suspension (intravenous amphotericin B in refractory cases)
  • Caspofungin
  • Voriconazole
• Oral hairy leukoplakia: Most lesions are asymptomatic and do not require treatment. Severe cases have responded to acyclovir. Relapses are common when acyclovir is discontinued, and maintenance therapy may be required.
• Aphthous ulcers: Topical anesthetics provide immediate symptomatic relief. Some studies also show improvement with thalidomide therapy.
• HSV and VZV
• • Acyclovir, famciclovir, or valacyclovir
  • Foscarnet for acyclovir-resistant strains
  • Maintenance therapy with acyclovir, famciclovir, or valacyclovir in patients with frequent recurrences
• Anemia: Patients with a low serum EPO level have an inflammatory component to their anemia. These patients benefit from recombinant epoetin alfa (Epogen) therapy. A target hemoglobin level of 11-13 g/dL has been recommended as a goal for epoetin alfa therapy. Otherwise, transfusions of packed red blood cells may help patients who are symptomatic from their anemia.
• Idiopathic thrombocytopenic purpura
• • Intravenous immunoglobulin and prednisone: Both high-dose intravenous immunoglobulin (eg, 0.4 g/kg/d infused for 3-5 d) and high-dose intravenous glucocorticoids (eg, prednisone 1-2 mg/kg/d) can induce transient increases in the platelet count, but they generally do not provide a sustained response. These therapies should be administered to patients with platelet counts less than 20,000/µL or with documented bleeding.
  • Zidovudine: Because HIV-induced thrombocytopenia is also due to the direct effect of the virus on megakaryocytes, antiretroviral therapy often helps provide more sustained increases in the platelet count. Treatment with AZT has been studied extensively and is associated with a significant increase in platelet counts in approximately 40-70% of patients.
  • Highly active antiretroviral therapy: Since the advent of highly active antiretroviral therapy, a combination of antiretroviral drugs that includes AZT is the treatment of choice for HIV-induced thrombocytopenia.
• Thrombotic thrombocytopenic purpura
• • Plasmapheresis
  • Concomitant therapy with corticosteroids (eg, prednisone at 1-2 mg/kg/d)
  • Vincristine in patients whose conditions are refractory to plasmapheresis
  • Splenectomy in refractory cases
  • Platelet transfusions - Contraindicated except in severely thrombocytopenic patients with documented bleeding
• Thrombocytopenia due to decreased platelet production (eg, drug toxicity, marrow infiltration): Platelet transfusions should be administered in cases of documented bleeding or should be given prophylactically to prevent bleeding episodes when the platelet count falls to less than 10,000/µL and the duration of thrombocytopenia is expected to be limited.
• Aseptic meningitis: Supportive measures are indicated.
• Acute inflammatory demyelinating polyneuropathy: The course generally is self-limited, and only supportive measures are needed. In severe cases, plasma exchange, intravenous immunoglobulin, or systemic glucocorticoids has been tried, with a variable response. Ganciclovir has also been used in late-stage disease, with a variable response.
• Mononeuritis multiplex: Early in the course of HIV infection, mononeuritis multiplex is usually limited to a single nerve or a few nerves and resolves spontaneously without treatment. Ganciclovir has also been used in late-stage disease, with a variable response.
• Myopathy: Patients infected with HIV who develop myopathy while taking AZT should either reduce the dosage or discontinue the medication. Approximately 20% of patients show some improvement after AZT is discontinued. For most patients, HIV myopathy is due directly to the virus. Data from some retrospective series suggest that treatment with prednisone (60 mg/d initially, taper as rapidly as possible) helps to improve strength.

Surgical Care

• Idiopathic thrombocytopenic purpura: Splenectomy is an option for patients whose conditions are refractory to medical treatment. Most patients with HIV-associated thrombocytopenia respond to this surgical treatment. Because of the risk of infections with encapsulated organisms, all patients infected with HIV, especially those who are about to undergo splenectomy, must be immunized with pneumococcal polysaccharide vaccine.
• Thrombotic thrombocytopenic purpura: Splenectomy is also an option in refractory cases of TTP, but the response rate is highly variable. Because of the risk of infections with encapsulated organisms, all patients infected with HIV, especially those who are about to undergo splenectomy, must be immunized with pneumococcal polysaccharide vaccine.

Consultations

Close collaboration with consultants (eg, infectious diseases specialists, dermatologists, gastroenterologists, hematologists, neurologists) is important and is directed by the constellation of illnesses manifested.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Drug Category: Antifungals

Mechanism of action may involve an alteration of RNA and DNA metabolism or an intracellular accumulation of peroxide that is toxic to fungal cells. Fluconazole and nystatin are the agents most commonly used to treat candidiasis. Ketoconazole and itraconazole are less frequently used. Recently approved agents include caspofungin (70 mg IV initial dose then 50 mg IV qd for 14-21 d) and voriconazole (200 mg bid PO or IV for 14-21 d). When systemic agents (eg, amphotericin B, caspofungin, or intravenous voriconazole) are administered, patients should be monitored for the adverse effects and associated complications common to the drugs.

Drug Category: Immunomodulators

Postulated mechanisms include free radical–mediated oxidative damage to DNA, decreased secretion of IL-6, IL-1-beta, IL-10, and TNF-alpha; reduced angiogenesis; induction of IFN-gamma; and IL-2 production by CD8 T cells.

Drug Category: Antivirals

Nucleoside analogs are initially phosphorylated by viral thymidine kinase to eventually form a nucleoside triphosphate. These molecules inhibit HSV polymerase with 30- to 50-times the potency of human alpha-DNA polymerase.

Drug Category: Glucocorticoids

Have anti-inflammatory properties and cause profound and varied metabolic effects. Modify body's immune response to diverse stimuli. Used for ITP, TTP, myopathy, and AIDP.

Drug Category: Antiretrovirals

Inhibitors of reverse transcriptase; thus, cause chain termination when incorporated into growing viral strand. Used to treat HIV infection and HIV-induced thrombocytopenia.

Drug Category: Growth factors

Used in anemia due to HIV infection to induce erythropoiesis.

Drug Category: Antineoplastics

Block mitosis by arresting cells in metaphase. Used in patients with TTP refractory to plasmapheresis.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Most of the conditions involved in early symptomatic HIV infection can be treated in an outpatient setting. Decisions for inpatient care are made on a case-by-case basis. Patients infected with HIV should be cared for by physicians with expertise in HIV infection because this has been shown to decrease patient morbidity and to extend patient lifespan.

In/Out Patient Meds

• See Treatment and Medication.

Prognosis

• Early symptomatic infection encompasses several diseases. Patients classified under this term are a heterogeneous group, with widely varying clinical problems and prognoses. This heterogeneity is the primary reason why many infectious disease specialists recommend against using the term AIDS-related complex.

Patient Education

• Counsel patients extensively about the course of HIV illness, therapeutic options, health maintenance issues (eg, vaccinations, abstinence, safe-sex practices, informing sexual partners about HIV diagnosis), and the range of conditions that can occur at each stage on the HIV continuum. Close follow-up care with physicians who have expertise in treating patients infected with HIV is essential.
• For excellent patient education resources, visit eMedicine's Immune System Center, Sexually Transmitted Diseases Center, and Teeth and Mouth Center. Also, see eMedicine's patient education articles HIV/AIDS, Rapid Oral HIV Test, Oral Herpes, and Canker Sores.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to identify patients who are at risk for HIV infection: One of the goals of this article is to remind clinicians that the numerous conditions discussed may be harbingers of HIV infection. A high index of clinical awareness is essential. A growing body of literature supports routine testing for HIV.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Aberg JA, Gallant JE, Anderson J, et al. Primary care guidelines for the management of persons infected with human immunodeficiency virus: recommendations of the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis. Sep 1 2004;39(5):609-29. [Medline].
• Arnaudo E, Dalakas M, Shanske S, et al. Depletion of muscle mitochondrial DNA in AIDS patients with zidovudine- induced myopathy. Lancet. Mar 2 1991;337(8740):508-10. [Medline].
• Bartlett JG. Abbreviated Guide to Medical Management of HIV Infection. Baltimore, Md: Johns Hopkins University, Department of Infectious Diseases; 2006. [Full Text].
• Bartlett JG, Gallant JE. Medical Management of HIV Infection. Baltimore, Md: Johns Hopkins University; 2006.
• Bartlett JG. Adult HIV/AIDS Treatment. Baltimore, Md: Johns Hopkins University, Department of Infectious Diseases; 2003.
• Bettaieb A, Fromont P, Louache F, et al. Presence of cross-reactive antibody between human immunodeficiency virus (HIV) and platelet glycoproteins in HIV-related immune thrombocytopenic purpura. Blood. Jul 1 1992;80(1):162-9. [Medline].
• Boyar A, Beall G. HIV-seropositive thrombocytopenia: the action of zidovudine. AIDS. Nov 1991;5(11):1351-6. [Medline].
• Brusamolino E, Malfitano A, Pagnucco G, et al. HIV-related thrombocytopenic purpura: a study of 24 cases. Haematologica. Jan-Feb 1989;74(1):51-6. [Medline].
• Castella A, Croxson TS, Mildvan D, et al. The bone marrow in AIDS. A histologic, hematologic, and microbiologic study. Am J Clin Pathol. Oct 1985;84(4):425-32. [Medline].
• Chalmers AC, Greco CM, Miller RG. Prognosis in AZT myopathy. Neurology. Aug 1991;41(8):1181-4. [Medline].
• Clumeck N. Choosing the best initial therapy for HIV-1 infection. N Engl J Med. Dec 16 1999;341(25):1925-6. [Medline].
• Coyle TE. Hematologic complications of human immunodeficiency virus infection and the acquired immunodeficiency syndrome. Med Clin North Am. Mar 1997;81(2):449-70. [Medline].
• Dominguez A, Gamallo G, Garcia R, et al. Pathophysiology of HIV related thrombocytopenia: an analysis of 41 patients. J Clin Pathol. Nov 1994;47(11):999-1003. [Medline].
• El-Sadr WM, Lundgren JD, Neaton JD, et al. CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med. Nov 30 2006;355(22):2283-96.
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Article Last Updated: Feb 20, 2007