Clinical Manifestations

Available scientific evidence suggests a dynamic process in which initial and ongoing immunological responses to HIV infection are not only unsuccessful in clearing HIV but, paradoxically, they are paralleled by a progressive reduction in immunocompetence.⁷ Individual variations exist, but a pattern of disease progression has been established as consisting of three phases: (1) primary infection, (2) a period of clinical latency, and, finally, (3) clinically apparent disease.⁷

After an incubation period of 1 to 3 weeks, 50% to 80% of patients experience an ill-defined Acute Retroviral Syndrome characterized by fever, lethargy, malaise, sore throat, arthralgia, myalgia, headaches, photophobia, maculopapular rash, and lymphadenopathy.^7,8 Antibodies can be detected 3 to 6 months after exposure. During clinical latency (8 to 24 months), the patient is free of overt signs and symptoms. Without appropriate antiretroviral therapy, an HIV-infected patient is at risk of developing a multitude of opportunistic infections, the most common of which are summarized in Table 1.⁹

Table 1. Opportunistic illnesses (AIDS-defining conditions).⁹

Bacterial infections, multiple or recurrent*
Candidiasis of bronchi, trachea, or lungs
Candidiasis, esophageal
Cervical cancer, invasive†
Coccidioidomycosis, disseminated or extrapulmonary
Cryptococcosis, extrapulmonary
Cryptosporidiosis, chronic intestinal (> one month’s duration)
Cytomegalovirus disease (other than liver, spleen, or nodes), onset at age > 1 month
Cytomegalovirus retinitis (with loss of vision)
Encephalopathy attributed to HIV§
Herpes simplex: chronic ulcer(s) (> month’s duration); or bronchitis,pneumonitis, or esophagitis (onset at age >1 month)
Histoplasmosis, disseminated or extrapulmonary
Isosporiasis, chronic intestinal (greater than one month’s duration)
Kaposi sarcoma
Lymphoma, Burkitt’s (or equivalent term)
Lymphoma, immunoblastic (or equivalent term)
Lymphoma, primary, of brain
Mycobacterium avium complex or Mycobacterium kansasii, disseminated or extrapulmonary
Mycobacterium tuberculosis of any site, pulmonary† or extrapulmonary
Mycobacterium, other species or unidentified species, disseminated or extrapulmonary
Pneumocystis jirovecii (previously known as Pneumocystis carinii) pneumonia
Pneumonia, recurrent†
Progressive multifocal leukoencephalopathy
Salmonella septicemia, recurrent
Toxoplasmosis of brain, onset at age > 1 month
Wasting syndrome attributed to HIV§

* Only among children aged <6 years
† Only among adults, adolescents, and children aged ≥6 years
§ Suggested diagnostic criteria for these illnesses, which might be particularly important for HIV encephalopathy and HIV wasting syndrome, are described in the following references:

CDC. 1994 Revised classification system for human immunodeficiency virus infection in children less than 13 years of age. MMWR 1994;43(No. RR-12).
CDC. 1993 Revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. MMWR 1992;41(No. RR-17).

HIV-induced immunosuppression places the patient at risk for numerous oral conditions (Table 2). The most notable are candidiasis (erythematous, pseudomembranous), hairy leukoplakia, Kaposi’s sarcoma, non-Hodgkin’s lymphoma, and periodontal disease (linear gingival erythema, necrotizing ulcerative periodontitis).^10-11 Hairy leukoplakia and oral candidiasis are positive predictors of HIV disease progression. Contemporary antiretroviral therapy significantly decreases this risk.¹² Indeed, for a patient on an antiretroviral regimen, the development of an HIV-associated oral manifestation may signal therapeutic failure.¹¹ If this occurs, the patient should be promptly referred to their managing physician for evaluation.

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Kaposi's Sarcoma

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Hairy Leukoplakia

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Oral Candidiasis

Table 2. Oral Lesions Associated with HIV Infection.^10,23

Group 1 Lesions strongly associated with HIV infection	Candidiasis Erythematous Pseudomembraneous Hairy leukoplakia Kaposi’s sarcoma Non-Hodgkin’s lymphoma Periodontal disease Linear gingival erythema Necrotizing (ulcerative) gingivitis Necrotizing (ulcerative) periodontitis
Group 2 Lesions less commonly associated with HIV infection	Bacterial infections *Mycobacterium avium-intracellularae* *Mycobacterium tuberculosis* Melanotic hyperpigmentation Necrotizing (ulcerative) stomatitis Salivary gland disease Dry mouth due to decreased salivary flow rate Swelling of major salivary glands Thrombocytopenia purpura Ulceration NOS (not otherwise specified) Viral infections Herpes simplex virus Human papillomavirus (warty-like) lesions *Condyloma acuminatum* Focal epithelial hyperplasia Verruca vulgaris Varicella-zoster virus Herpes zoster Varicella
Group 3 Lesions seen in HIV infection	Bacterial Actinomyces israelii Escherichia coli Klebsiella pneumonia Cat-scratch disease Drug reactions (ulcerative, erythema multiforme, lichenoid, toxic epidermolysis) Epithelioid (bacillary) angiomatosis Fungal infection other than candidiasis Cryptococcus neoformans Geotrichum candidum Histoplasma capsulatum Mucoraceae (mucormycosis zygomycosis) Aspergillus flavus Neurological disturbances Facial palsy Trigeminal neuralgia Recurrent aphthous stomatitis Viral infections Cytomegalovirus *Molluscum contagiosum*

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