Clinical History:

An 18-year-old noted fever of one week duration along with sore throat, mild diarrhea, headache, and generalized aching. She saw her family physician who noted pharyngitis, generalized lymphadenopathy, and a very mild diffuse erythematous rash on her extremities and trunk on physical examination. The physician suspected an acute viral illness such as infectious mononucleosis, but a monospot test was negative and her symptoms were still present two weeks later. Further history indicated that she had multiple episodes of unprotected sexual intercourse with several partners over the past two months.

Answers:

1. What tests should you consider obtaining next?

The history suggests the possibility of sexually transmitted diseases (SDs). The most common of these, gonorrhea and syphilis, do not have a presentation similar to this case, as neither has a pharyngitis and the extent of the systemic signs and symptoms. An STD with features similar to infectious mononucleosis is acute HIV infection. Consent for HIV testing in many places must be obtained from the patient (or parent or guardian in the case of minors).

2. What are the major risk factors for HIV infection?

The major risk relate to the mode of transmission for HIV, which are:

• as a sexually transmitted disease
• by parenteral means
• as a congenital infection



In the United States, about 50 to 60% of AIDS cases occur in homosexual/bisexual males, about 20 to 25% in intravenous drug users, and about 15% in heterosexual adults. Congenital infections account for less than 1% of cases. Transfusion associated AIDS has essentially disappeared with routine testing of blood products since 1985. In some parts of the world, the heterosexual cases comprise half the total.

3. What is the nature of this patient's acute illness?

This patient has an acute HIV illness. This is seen in about half of HIV infections and often goes unnoticed because the signs and symptoms are usually not severe and resemble other mild viral illnesses, such as a cold or infectious mononucleosis.

4. How reliable is the HIV test? What is the result for the patient in lane A in the test above?

The initial screening ELISA test is very reliable, with sensitivity and specificity greater than 99%. However, no HIV test is reported as positive until confirmed by Western Blot testing, as shown in figure 1.2. In rare cases, as with patient A, the Western blot is "indeterminate" and additional testing (such as p24 antigen) or retesting in 6 months may be necessary. A result similar to lane C will be interpreted as negative. Lack of seroconversion following HIV infection is extremely rare.

5. What is this patient's stage of HIV infection?

Her Stage is A, as she has not developed other illnesses associated with HIV, only an acute HIV infection. A CD4 lymphocyte count, if performed, would probably show >500 cells/microliter, and she would be in Stage A1. The CD4 count declines with acute HIV infection, then rebounds, though not to pre-infection levels, then declines over years as the immune system granually fails.

Diagnostic Criteria for AIDS

The Centers for Disease Control (CDC) have continued to evolve criteria for diagnosis, reporting, and clinical staging of AIDS in the United States based upon knowledge about HIV, available laboratory testing, and clinical course. The 1993 revised classification system for HIV infection and AIDS surveillance case definition for adolescents (greater than or equal to 13 years) and adults is based upon three clinical categories, each subdivided into three CD4 lymphocyte count categories.

Criteria for diagnosis of HIV infection include any of the following:

• Repeatedly reactive screening tests for HIV antibody (e.g., ELISA) with specific antibody identified by the use of supplemental tests (such as Western blot or immunofluorescence assay); or
• Direct identification of HIV in host tissues by virus isolation; or
• HIV antigen detection; or
• A positive result on any other highly specific licensed test for HIV.

The subdivisions of the above categories are made according to the CD4 lymphocyte count as follows:

Categories  A1,  B1,  C1:	CD4 count is  > or = 500 cells/microliter
Categories  A2,  B2,  C2:	CD4 count is  200 to 499 cells/microliter
Categories  A3,  B3,  C3:	CD4 count is  <200 cells/microliter,
                                               or <14% CD4 cells

     A = asymptomatic
     B = onset of non-life threatening opportunistic infections
           such as Candida
     C = onset of life threatening opportunistic infections and
           neoplasms characteristic for AIDS

DIAGNOSIS OF AIDS: All persons within Category C as well as all persons in subset 3 with a CD4 lymphocyte count of <200/microliter (or <14% CD4 cells) meet surveillance criteria for a definition of AIDS.

As the CD4 count drops, the HIV-1 RNA level increases. The HIV-1 RNA level is more useful than CD4 count for monitoring responses to antiretroviral therapies.