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Case 3: Discussion

Preventing and treating infectious complications associated with HIV infection plays a major role in the management of HIV-infected persons. Determining the risk of past and ongoing risks for acquiring infections is an important goal of the initial history and laboratory evaluation. Key aspects of the history include past and current sexual practices, history of sexually transmitted diseases, history of injection drug use, travel or prior residence in an area endemic for fungal diseases, history of (or exposure to a person with) tuberculosis, and animal contact. Serologic testing can provide specific laboratory evidence of prior infection and can guide prevention efforts. Patients without evidence of prior infection can receive counseling for specific means to prevent infection, and those with evidence of prior infection may be candidates for specific preventive treatments. Recommended routine serologic tests to order for the initial evaluation of all HIV-infected patients are listed in Figure 1.

Bacterial Infections

After declining every year from 1990 to 2000, the reported number of cases of Treponema pallidum infection manifested as either primary or secondary syphilis increased significantly from 2000 to 2004[1]. This trend reversal has corresponded with several reports of outbreaks of syphilis among men who have sex with men, including high rates of HIV infection among these men (Figure 2). All HIV-infected adults, especially men who have sex with men, those with a history of sexually-transmitted diseases, and patients who have unprotected intercourse, should be screened for syphilis with the rapid plasma reagin (RPR) or Venereal Disease Research Laboratory (VDRL) assay. Those patients with negative syphilis tests and who have ongoing risk should undergo periodic retesting for syphilis, typically every 6 to 12 months.

Cats can transmit Bartonella henselae to humans. This organism can potentially cause serious disease in HIV-infected persons with advanced immunosuppression. Cats younger than 1 year of age pose the greatest risk of transmitting B. henselae. Accordingly, patients should avoid cat scratches. If a scratch does occur, they should wash the affected area promptly and thoroughly. Routine serologic testing of cats or HIV-infected persons to detect past infection with Bartonella has unknown utility and is not recommended[2].

Mycobacterium tuberculosis and a number of non-tuberculous mycobacteria (especially M. avium complex) are important pathogens in HIV-infected patients. Skin testing using purified protein dervivative (PPD) of M. tuberculosis is recommended for all HIV-infected persons. Serologic tests to detect prior infection with M. avium complex or other non-tuberculous mycobacteria are not available, and blood cultures for M. avium complex are used for diagnostic purposes in symptomatic patients with advanced HIV disease, but not for routine screening.

Viral Infections

All HIV-infected individuals should undergo screening for prior infection with hepatitis A virus (HAV), hepatitis B virus (HBV), and hepatitis C virus (HCV). Among HIV-infected persons, evidence of HCV infection varies significantly depending on the risk factor for acquiring HIV (Figure 3), with infection rates of 60 to 90% among injection drug users, 4 to 10% among men who have sex with men, and 5 to 14% of those who acquired HIV heterosexually[3,4]. Those patients with chronic HBV or HCV infection who are co-infected with HIV have a greater risk of progression to chronic liver disease and may have a more rapid progression of HIV disease[4,5]. The HCV enzyme immunoassay is recommended as the initial screening test and those persons with a positive test should undergo confirmatory testing with either supplemental antibody testing (RIBA) or a test to detect the presence of HCV RNA[5]. Screening for HBV should include antibody testing (anti-HBs and anti-HBc) plus antigen testing (HBsAg).

Evidence of prior infection with cytomegalovirus (CMV) has been found in greater than 90% of HIV-infected men who have sex with men and in greater than 70% of HIV-infected injection-drug users[6]. According to USPHS/IDSA guidelines, HIV-infected persons should undergo CMV antibody testing (anti-CMV IgG) only if they have a relatively low risk for CMV, namely those who have not had male-to-male sex contact and those who have not used injection drugs[2]. Persons in high-risk groups for acquiring CMV disease are generally assumed seropositive for CMV. Routine screening for CMV infection using non-serologic laboratory markers, such as CMV antigen or quantitative CMV PCR, is not recommended. Those HIV-infected persons who are CMV seronegative can receive counseling on how to prevent exposure to CMV and, if they require a blood transfusion, they should receive CMV-negative blood products.

Routine serologic testing for herpes simplex virus (HSV) types 1 and 2 historically has not been recommended. More recently, however, some experts have recommend performing HSV serologic testing in HIV-infected persons to help identify unrecognized or asymptomatic HSV-2 infection[7]. Serologic testing for varicella zoster virus (VZV) with anti-varicella IgG is should be considered for patients who do not recall having had chicken pox, in order to determine in advance the need for postexposure prophylaxis in the event of a VZV exposure. Human herpesvirus-8 (HHV-8), the agent responsible for Kaposi's sarcoma, Castleman's disease, and primary effusion lymphoma, occurs most frequently among men who have sex with men and transmission presumably occurs through contact with saliva, blood, and semen[8]. Clinical use of routine serologic testing has not been established.

Parasitic Infections

Approximately 20 to 30% of HIV-infected adults in the United States have serologic evidence of prior infection with Toxoplasma gondii[9]. In contrast, Toxoplasma infection occurs in up to 80% of the general population in France and among persons in certain regions of Africa. Because toxoplasmic encephalitis nearly always represents reactivation disease in HIV-infected patients, knowledge of Toxoplasma serostatus can prove extremely useful when evaluating an HIV-infected person with a brain mass lesion, though it does not establish or exclude the diagnosis. In addition, Toxoplasma serostatus can identify persons who should receive prophylaxis for Toxoplasma disease. Patients without prior exposure to Toxoplasma should receive counseling on ways to reduce the risk of Toxoplasma infection, most importantly by avoiding contact with cat feces and by not eating undercooked red meat. Although other parasitic infections, such as cryptosporidiosis, isosporiasis, and microsporidiosis, can cause significant disease in HIV-infected persons, routine serologic tests for these pathogens are not recommended.

Fungal Infections

Skin testing with histoplasmin and serologic testing for prior infection with Histoplasma capsulatum do not predict subsequent development of histoplasmosis in HIV-infected persons, and thus these tests are not recommended. Histoplasma antigen tests are useful for the diagnosis of histoplasmosis in patients presenting with a compatible clinical syndrome, but have no role in routine screening. Similarly, skin testing with coccidioidin and serologic testing for prior infection with Coccidioides immitis are not recommended. Routine serologic or antigen testing for infection with Cryptococcus neoformans is also not recommended. The serum cryptococcal antigen test is used for diagnosis of acute cryptococcal disease, and should not be used for routine screening. Serologic testing or antigen testing for prior infection with Candida species is not recommended. Exposure to Candida is universal and cannot be prevented.

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    Figure 1. Recommendations for Serologic Testing at Initial Evaluation of HIV-Infected Persons)

    These are tests recommended to screen for evidence of past, and in some instances, current infection.

    Figure 1
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    Figure 2. Reported Cases of Primary and Secondary Syphilis in United States, 1981-2001

    This graph illustrates the dramatic decrease in syphilis cases during the 1990’s among both women and men. Among men, the trend began to reverse in 2001. Adapted from Primary and secondary syphilis—United States, 2000-2001. MMWR 2002; 51:971-3.

    Figure 2
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    Figure 3. Hepatitis C Virus Prevalence Rates Depending on HIV Risk Factor

    These hepatitis C virus prevalence rates among HIV-infected persons are obtained from HIV-infected persons receiving medical care at the John’s Hopkins HIV clinic (n = 1955). As shown, rates vary significantly based on underlying risk factor for acquiring HIV. The HIV risk factor is according to the patient’s self report exposure category. This figure is adapted from Sulkowski MS, Thomas DL. Hepatitis C in the HIV-infected person. Ann Intern Med 2003; 138:197-207. This figure is adapted from and reproduced with permission from the American College of Physicians.

    Figure 3