Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (500 page)

   HIV transmission is due to direct contact with infected body fluids, primarily blood, semen, vaginal and cervical secretions, breast milk, and amniotic fluid. This contact is usually mediated by sexual contact, IV drug abuse, blood exposure (transfusion, transplantation, needlestick injury), and vertical transmission (pregnancy, childbirth, and nursing). The relative contribution of these modes shows regional variability. The risk of transmission depends on a number of factors, including viral load in infected fluid, presence of other STDs, sexual history, having an infected partner who is uncircumcised, and genetic factors.

   HIV is able to infect cells that express CD4 on their surfaces, primarily CD4
⁺
T lymphocytes and macrophages.

   Who Should Be Suspected?

HIV-1 infection may be divided into three clinical phases:

   
Acute phase
: During the acute phase, which usually occurs between 1 and 4 weeks after exposure, there is viremia with infection of cells throughout the body. The HIV-1 plasma viral load is markedly elevated, typically >10
⁶
copies/mL. The level of CD4
⁺
T lymphocytes is reduced, due to destruction and sequestration.

   Thirty to seventy percent of patients develop nonspecific symptoms. A mononucleosis-type syndrome is common. Symptoms include headache, fever, malaise, pharyngitis, myalgias, and arthralgias. A nonpruritic macular rash commonly develops on the face and trunk. Generalized lymphadenopathy is common. Other symptoms include ulcerations of skin and mucous membranes, nausea, vomiting, and diarrhea. Neurologic symptoms, including aseptic meningoencephalitis and neuropathy, may develop.

   Symptoms typically resolve within 4 weeks.

   
Asymptomatic or minimally symptomatic phase
: The acute phase is followed by a phase, typically prolonged, where the patient is not severely immunocompromised and symptoms may be absent or mild. During this time, there is continued viral replication and CD4
⁺
T-lymphocyte depletion. The rate of loss of CD4 cells is related to the HIV-1 viral load.

   During this phase, fatigue and lymphadenopathy may be seen. Other manifestations may include bacillary angiomatosis, cervical dysplasia or carcinoma in situ, chronic diarrhea, oral leukoplakia, progressive fatigue, progressive weight loss, night sweats, recurrent shingles or zoster in multiple dermatomes, and/or vaginal or oral candidiasis.

   This second phase of infection usually lasts for 8–10 years before progression to AIDS.

   
AIDS/symptomatic phase
: The relentless depletion of CD4 cells eventually results in profound immunosuppression and the clinical manifestations of AIDS. A specific diagnosis of AIDS is based on laboratory findings and the presence of AIDS-defining infections or malignancies, including candidiasis, cervical cancer, recurrent infections, coccidiomycosis, cryptococcosis, cryptosporidiosis, encephalopathy, histoplasmosis, Kaposi sarcoma, lymphoma,
Mycobacterium tuberculosis
infection, progressive multifocal leukoencephalopathy,
Pneumocystis
pneumonia, CNS toxoplasmosis, and wasting syndrome (unintentional loss of >10% of body weight).

   Diagnosis and Staging