Approach to the Patient with Human Immunodeficiency Virus (HIV) Infection
Stephen L. Boswell
Despite the fact that a cure remains elusive, the management of the patient infected with human immunodeficiency virus (HIV) has improved significantly in recent years. Most care is now conducted in the outpatient setting, even for patients with acquired immunodeficiency syndrome (AIDS). Earlier intervention, new therapies, and innovative strategies to prevent secondary infections have significantly decreased morbidity and increased survival. With the shift in management to the outpatient setting, primary care physicians have assumed an increasingly central role in the comprehensive care of the HIV-infected patient; they are responsible for initial diagnosis, counseling, prevention of spread, initiation of antiviral and prophylactic therapies, outpatient treatment of secondary infection, determination of need for hospitalization, and provision of supportive care in the late stages of illness. This requires that the primary care physician be knowledgeable about HIV risk behaviors, disease manifestations, laboratory studies, current therapy, and prophylaxis strategies. If taking primary responsibility for HIV care, the primary care physician should work with the support of an expert in HIV care as treatment often requires complex multidrug programs that continue to evolve.
Case Definitions
HIV Infection
The Centers for Disease Control and Prevention (CDC) criteria for HIV infection (HIV or HIV-2) in patients older than 18 months of age include the following:
A positive result on a screening test for HIV antibody (e.g., repeatedly reactive enzyme immunoassay), followed by a positive result on a confirmatory test for HIV antibody (e.g., Western blot or immunofluorescence antibody test)
A positive result or report of a detectable quantity on any of the following HIV virologic (nonantibody) tests: HIV nucleic acid (DNA or RNA) detection (e.g., DNA polymerase chain reaction [PCR] or plasma HIV RNA); HIV p24 antigen test, including neutralization assay; and HIV isolation (viral culture)
AIDS
In 1993, the CDC revised the criteria for the definition of AIDS to incorporate clinical presentations in women and heterosexuals and advances in understanding the significance of counts of CD4+ lymphocytes (also known as helper T lymphocytes or CD4 cells). This CDC surveillance definition of AIDS requires the following:
CD4+ T lymphocyte count less than 200 cells/mm3 (or CD4+ T lymphocyte percentage <14%) and laboratory evidence of HIV infection
Presence of an AIDS-indicator disease (candidiasis of the esophagus, trachea, bronchi, or lungs; invasive cervical cancer; extrapulmonary Coccidioidomycosis; extrapulmonary cryptococcosis; cryptosporidiosis with diarrhea for more than 1 month; cytomegalovirus (CMV) infection of any organ other than the liver, spleen, or lymph nodes; herpes simplex infection with mucocutaneous ulcer for more than 1 month or bronchitis, pneumonitis, or esophagitis; extrapulmonary histoplasmosis; HIV-associated dementia; HIV-associated wasting; isosporiasis with diarrhea for more than 1 month; Kaposi sarcoma in a patient younger than 60 years of age; disseminated Mycobacterium avium; pulmonary or extrapulmonary tuberculosis (TB); Pneumocystis jiroveci pneumonia; recurrent bacterial pneumonia; progressive multifocal leukoencephalopathy; recurrent Salmonella septicemia (nontyphoid); and toxoplasmosis) and laboratory evidence of HIV infection
Epidemiology
HIV epidemic is a pandemic. It has become one of the world’s leading infectious causes of death, recently accounting for an estimated 2.9 million deaths/year from AIDS-related causes. It moved to this position from relative obscurity when five cases of AIDS were reported in Los Angeles in 1981. HIV has spread most rapidly in Asia and sub-Saharan Africa, with more than 8.6 million and 24.7 million cases, respectively. The epidemic continues to expand in South America, but the rate of increase has slowed in North America and Europe. In developing countries, the virus is spread primarily through heterosexual contact and affects males and females on a more equal basis than in Western countries.
In the United States, more than 1.1 million individuals are now infected with HIV, and the numbers continue to rise at a rate of about 56,000 per year. It is estimated that about 235,000 are infected but unaware of their status. The epidemic continues to disproportionately affect men who have sex with men (MSM), especially young black MSM. Heterosexuals now account for approximately one in four new HIV infections. The incidence of HIV infection has dropped slightly among injection drug users. Those at highest risk of infection include
MSM and their sexual contacts
Intravenous drug users and their sexual contacts
Persons who received blood and blood products prior to 1985
Children born to infected women
The risk of directly acquiring HIV infection through processed blood or selected blood products (plasma and clotting factor concentrates) has dramatically decreased since 1985 as a consequence of the widespread screening of those who donate blood and plasma, the use of serologic tests for HIV, and the viral inactivation of various plasma products. Perinatal transmission has dropped significantly due to the use of chemoprophylaxis.
Most individuals infected with HIV in the developed world have no signs or symptoms of their infection. Such individuals often present to health care providers for problems related to high-risk activity (e.g., intravenous drug use, sexual transmitted infections), unaware that they are carrying HIV. These encounters provide a critical opportunity to identify and reach out to persons with HIV infection (see Chapter 7).
Pathophysiology
The HIV is an RNA retrovirus that includes a core protein (p24), a reverse transcriptase, an HIV protease, and envelope glycoproteins. Isolates of HIV differ genetically and antigenically, particularly in regard to envelope proteins (a feature that has complicated development of an effective vaccine).
HIV is transmitted through sexual contact, parenteral exposure to blood and selected blood products, and maternal transmission (via breast milk and perinatal transmission). Once the virus enters the body, it eventually attaches to the surface of CD4+ T lymphocytes. These helper T lymphocytes are the target of HIV by virtue of the virus’s affinity for receptors on their surface. Once attached, the virus enters the lymphocyte and removes its coat. Its RNA is transcribed to DNA by reverse transcriptase. The DNA may remain in the cytoplasm or become integrated into the host cell genome, where it can remain latent until a stimulus triggers replication of virus.
Billions of viral particles are produced in an untreated infected person each day. Most of these viral particles are produced by activated CD4+ lymphocytes, which are killed when the virus enters the lytic stage of infection. These cells are central to the maintenance of immunocompetence. With damage to the CD4 cell population, patients are at increased risk for clinical manifestations directly associated with the disease, including HIV encephalopathy and HIV-associated wasting. As HIV infection progresses, the risks of opportunistic infection and neoplasm increase. Untreated, death occurs most frequently because of wasting, opportunistic infection, or neoplasm.
Clinical Presentations and Course
HIV infection in humans is a continuum that can be crudely broken into four phases: (a) primary HIV infection, (b) asymptomatic infection, (c) symptomatic infection excluding AIDS, and (d) AIDS. The rate of disease progression varies from person to person and depends on both viral and host factors. In general, the use of antiretroviral therapy (ART) and chemoprophylaxis of opportunistic infection have a profound effect on the pace of disease progression.
Primary Infection
This first phase of the illness is brief and consists of a mononucleosis-like syndrome. It occurs 1 to 4 weeks after transmission. In the initial years of the epidemic, the syndrome was not recognized, but after the development of serologic tests, it became possible to link HIV to this clinical syndrome. The syndrome consists of fever, sweats, lethargy, malaise, myalgias, arthralgias, headaches, photophobia, diarrhea, sore throat, lymphadenopathy, and a truncal maculopapular rash. It is of sudden onset and lasts 3 to 14 days. More than 50% of individuals infected with HIV experience one or more of these symptoms. Less frequently, neurologic signs and symptoms occur, such as those of meningoencephalitis, myelopathy, peripheral neuropathy, and Guillain-Barré syndrome. The most common neurologic symptoms in primary HIV infection are headache and photophobia. The symptoms that most markedly differentiate seroconversion subjects from control subjects are swollen lymph nodes, truncal or generalized rash, depression, irritability, anorexia, weight loss, and retro-orbital pain. Unfortunately, these symptoms are not specific for primary HIV infection.
Asymptomatic Seropositivity
This second phase of untreated HIV infection is the longest of the four phases and is also the most variable. Without treatment, this phase typically lasts 4 to 8 years and is distinguished by the lack of overt evidence of HIV infection.
Symptomatic Seropositivity (Pre-AIDS)
The onset of the third phase of untreated HIV infection ushers in the first physical evidence of immune system dysfunction. Persistent generalized lymphadenopathy (PGL) is often an early sign of this phase. Localized fungal infections of the toes, fingernails, and mouth frequently occur. Among women, recalcitrant vaginal yeast and trichomonal infections often recur. Oral hairy leukoplakia, one of the most commonly missed signs of HIV infection, is very prevalent and typically found on the tongue. Cutaneous manifestations of this phase of illness include widespread warts, molluscum contagiosum, exacerbations of psoriasis, and seborrheic dermatitis. Multidermatomal herpes zoster and an increased severity or frequency of herpes simplex infections can occur. Constitutional symptoms including night sweats, weight loss, and diarrhea are often seen. Without treatment, the duration of this phase is typically 1 to 3 years.
Acquired Immunodeficiency Syndrome
AIDS is characterized by significant immune suppression. This suppression leads to the development of disseminated opportunistic infections and unusual malignancies. Pulmonary, gastrointestinal, neurologic, and systemic symptoms are common.
Pneumocystis jiroveci Pneumonia.
This is among the most common infections in AIDS patients, with an attack rate of almost 80% in patients not receiving primary prophylaxis. Fever, night sweats, malaise, and weight loss typically precede the onset of pulmonary symptoms by days to weeks. A dry cough may be the first pulmonary manifestation, followed by shortness of breath. Diffuse infiltrates on chest radiograph, widening alveolar-arteriolar oxygen gradient (>30 mm Hg), and a low oxygen pressure (<50 mm Hg) are associated with reduced survival.
Fungal Infections.
Pulmonary and disseminated forms of invasive fungal infection with Cryptococcus neoformans, Histoplasma capsulatum, and Coccidioides immitis are other hallmarks of AIDS. Cryptococcal infection occurs throughout the United States and often presents subtly, with headache, fever, and malaise. Altered mentation and stiff neck are absent in most cases. At times, pulmonary complaints dominate the clinical picture of cryptococcal infection. Pulmonary and systemic complaints are prominent in patients with histoplasmosis or coccidioidomycosis. Infiltrates on chest film of a patient living in an endemic area suggest the diagnosis; splenomegaly can be marked in histoplasmosis.
Mycobacterial Infections.
Mycobacterial infections, both pulmonary and disseminated, are consequences of falling CD4 cell counts. HIV-seropositive patients with latent Mycobacterium tuberculosis infection are at increased risk of reactivation and dissemination. Meningeal involvement is the most common form of disseminated disease. Many strains isolated from AIDS patients demonstrate multiple-drug resistance (see Chapter 49). Mycobacterium avium-intracellulare infection accompanies very advanced disease. The clinical presentation is one of wasting, fever, sweats, diarrhea, and weight loss. Blood cultures are often positive.
Recurrent Bacterial Pneumonia.
Recurrent bacterial pneumonia (two or more episodes per year) can be a manifestation of AIDS. The presentations and organisms are typical of those
for bacterial pneumonia, with positive sputum cultures and infiltrates on chest radiograph. Such pneumonias are 20 times more common in HIV patients with low CD4 cell counts (<200 cells/mm3) than in those with normal counts. The recurrent development of such pneumonias represents significant immunosuppression.
for bacterial pneumonia, with positive sputum cultures and infiltrates on chest radiograph. Such pneumonias are 20 times more common in HIV patients with low CD4 cell counts (<200 cells/mm3) than in those with normal counts. The recurrent development of such pneumonias represents significant immunosuppression.
Cytomegalovirus Infection.
CMV infection, often due to reactivation of latent disease, is common in AIDS. Retinitis, presenting as unilateral visual loss or floaters and, if untreated, progressing to bilateral disease and blindness, afflicts about 5% to 10% of AIDS patients. Exudates and hemorrhages are noted on fundoscopic examination. Esophagitis, gastritis, and colitis also may develop.
Enteric Infection.
Enteric infections cause much morbidity for AIDS patients and typically present as weight loss, cramping pain, and large-volume diarrhea. Salmonella, Shigella, and Campylobacter are the leading causes, with the last two more characteristically presenting with bloody diarrhea and leukocytes on Wright stain of a fecal smear. Cryptosporidia, a protozoan, are important cause of diarrhea in AIDS patients in undeveloped areas of the world.
HIV Wasting Syndrome.
This syndrome is characterized by profound involuntary loss of more than 10% of body weight in conjunction with either chronic diarrhea (two or more stools per day for >1 month) or fever and persistent weakness for a similar period in the absence of another cause.
Neurologic Injury.
Nerve damage from HIV infection ranges from mild peripheral neuropathy causing paresthesias to encephalopathy with debilitating dementia. The virus appears to be neurotropic, causing significant neurologic injury in up to 30% of AIDS patients. HIV-associated dementia results from direct injury to neurons from HIV invasion of the central nervous system (CNS). Early on, there may be only minor impairment of cognitive or motor function, but in later stages, frank dementia and disabling motor disturbances ensue. Neuroimaging studies may show diffuse atrophic changes.
Opportunistic CNS Infections.
Toxoplasmosis is one of the most common of these. Most Toxoplasma gondii disease represents the reactivation of latent infection. About one third of patients who are immunoglobulin G (IgG) seropositive experience reactivation. CNS involvement can cause symptoms both of a mass lesion (discrete deficits, headache) and encephalitis (fever, altered mental status). The images on scanning by computed tomography or magnetic resonance imaging are characteristic: multiple (more than three) contrast-enhanced mass lesions in the basal ganglia and subcortical white matter.
Syphilis.
Syphilis is of increased likelihood in HIV patients with a history of high-risk sexual behavior, and it may take an atypical or accelerated course, including CNS spread.
Malignancies.
A consequence of the reduction in cellular immunity, Kaposi sarcoma, non-Hodgkin lymphoma, and primary CNS lymphoma occur with increased frequency in the setting of HIV infection and serve to define the onset of AIDS. Kaposi sarcoma is characterized by raised violaceous nonblanching plaques or nodules on the skin or mucus membranes. Visceral involvement may occur, presenting as hematemesis, melena, or hematochezia. A mass lesion on neuroimaging study may represent a primary CNS lymphoma, especially in a patient free of the encephalopathic findings that occur with toxoplasmosis of the CNS. Such lymphomas are rare except in the context of HIV infection. There is a 10-fold increase in the incidence of cervical dysplasia in HIV-seropositive women. The development of invasive cervical cancer is indicative of severe immune compromise.
Skin Conditions.
In addition to Kaposi sarcoma, other skin conditions are an important source of morbidity. They range from severe seborrheic dermatitis to cellulitis and drug eruptions. Frequency increases with worsening of immune function. Drug reactions are particularly common, with trimethoprim-sulfamethoxazole, dapsone-trimethoprim, and aminopenicillins most often implicated.
Lipodystrophy Syndrome.
Fat distribution changes, including central fat gain and peripheral fat loss in association with insulin resistance and dyslipidemia, have been associated with HIV infection and highly active antiretroviral therapy (HAART). The relationship between ART and these changes remains complex and poorly understood, but several older nucleoside analogues (e.g., the dideoxynucleotides, stavudine, didanosine, and zalcitabine) are associated with peripheral and facial fat loss, and the protease inhibitors (PIs) appear to be most closely linked to central (abdominal and dorsocervical spine) fat accumulation.
Prognosis
Prognosis strongly correlates with CD4 cell count and is inversely related to HIV viral load. Asymptomatic HIV-seropositive patients with CD4 cell counts greater than 500 cells/mm3 and a low viral load may remain otherwise healthy without treatment for many years. However, as HIV infection progresses, patients are at increased risk for clinical manifestations directly associated with the disease (see prior discussion). Without treatment, death is usually caused by opportunistic infection or malignancy. Increasingly, comorbid conditions such as hepatitis C infection are playing an important role in HIV mortality. Earlier intervention in HIV infection can significantly postpone the onset of AIDS and improves overall survival and quality of life (see Management).
Diagnosis of HIV Infection
The diagnosis of HIV infection is usually made serologically, by the presence of persistent HIV antibody positivity (Table 13-1). Alternative diagnostic methods include virus isolation and HIV antigen detection. The very sensitive ELISA method (enzyme-linked immunosorbent assay) is used for HIV antibody screening, with positive tests subjected to the more specific Western blot analysis for confirmation. Sensitivity and specificity of the ELISA are in the range of 99%. Most infected patients produce antibody to HIV within 6 to 8 weeks of transmission. Fifty percent have a positive result by 3 to 4 weeks, and nearly all have detectable antibody by 6 months. Occasionally, it is necessary to attempt direct detection of the virus (using such methods as viral culture, PCR, HIV signal amplification [branched DNA assay], or p24Ag) when clinical suspicion of acute HIV infection is high, but standard screening tests are negative.
Diagnosis of AIDS
The diagnosis of AIDS has become less important for clinical management as treatment for HIV infection has become more effective. A diagnosis of AIDS is useful primarily for historical and epidemiologic reasons (Table 13-1). When the HIV epidemic was first recognized, the diagnosis of AIDS was predominantly a clinical one, based on the identification of an indicator condition. However, the initial AIDS definition emphasized conditions seen in HIV-infected gay men and omitted attention to CD4 cell count and to presentations in other populations, such as women and heterosexuals. These shortcomings were
addressed in the 1993 CDC surveillance definition of AIDS (see prior discussion), which expanded the list of indicator conditions to include pulmonary TB, invasive cervical cancer, and recurrent pneumonia in patients who are HIV seropositive. In addition, the importance of immune status is acknowledged in these diagnostic criteria, with HIV-seropositive patients having a CD4 cell count less than 200 (<15% of lymphocytes) included among those considered to have AIDS.
addressed in the 1993 CDC surveillance definition of AIDS (see prior discussion), which expanded the list of indicator conditions to include pulmonary TB, invasive cervical cancer, and recurrent pneumonia in patients who are HIV seropositive. In addition, the importance of immune status is acknowledged in these diagnostic criteria, with HIV-seropositive patients having a CD4 cell count less than 200 (<15% of lymphocytes) included among those considered to have AIDS.
TABLE 13-1 Laboratory Testing | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Once a diagnosis of HIV infection has been made, the goals of the workup are to identify the stage of illness, determine prognosis, and promptly identify complications of immunoincompetence. Progression of immune system damage is a major concern. Patients with falling CD4 cell counts and high viral loads (>100,000 copies/mL) are at particularly high risk and should be treated promptly and followed closely.
History
The initial interview of the HIV-infected patient should seek information about infections, malignancies, and exposures that may indicate ongoing immune dysfunction or the potential for comorbid conditions. A review of sexual practices helps to define special categories of risk, such as MSM.
Past Medical History
Past medical history is carefully reviewed for a previous diagnosis of herpetic infections; aseptic meningitis; recurrent sinusitis; skin problems such as folliculitis, staphylococcal infections, psoriasis, molluscum contagiosum, warts, persistent tinea, or seborrhea; recurrent bacterial pneumonia due to encapsulated organisms (Haemophilus influenzae, pneumococci); oral and vaginal candidiasis; abnormal Papanicolaou smear results; sexually transmitted diseases (if there is a history of syphilis, the details of treatment and serologic titers should be carefully documented); hepatitis B infection or vaccination; hepatitis C infection; TB (including history of skin testing, exposures, chest radiographs, vaccination, prophylaxis, and treatment); and gastrointestinal infections with parasitic organisms or bacterial pathogens. A travel history may be useful in assessing the risk of exposure to histoplasmosis and coccidioidomycosis.
Review of Systems
Because HIV infection is usually a multisystem disease, the review of systems takes on particular importance. It begins with inquiry into systemic symptoms (fever, chills, drenching night sweats, fatigue, weight loss), which may be manifestations of acute infection or more advanced disease. Skin complaints should be reviewed, particularly reports of violaceous nodules or plaques, pustules, petechiae, groin rashes, or herpetic lesions. Moving to the head, eyes, ears, nose, and throat review, it is important to ask about sinus pain and any purulent drainage, sore throat, coated tongue, and white patches in the pharynx. Inquiry into lymphadenopathy may prove informative.
The pulmonary review includes a check for dyspnea, persistent dry or productive cough, and hemoptysis. A nonproductive cough of recent onset in conjunction with dyspnea on exertion should raise suspicion for Pneumocystis pneumonia. Patients should be asked about gastrointestinal symptoms, especially odynophagia (painful swallowing suggestive of fungal esophagitis), abdominal pain, nausea, vomiting, diarrhea, melena, hematochezia, hematemesis, tenesmus, and perianal pain. Diarrhea and tenesmus suggest large-bowel pathology. Cramping periumbilical pain, diarrhea, and increased flatus point to a small-bowel process. Early satiety, anorexia, and weight loss may be manifestations of gastrointestinal lymphoma. Genitourinary involvement is screened by inquiry into abnormal vaginal bleeding or discharge, dyspareunia, urinary frequency, dysuria, and hematuria.
The neurologic review is critical. Unilateral headache becoming more generalized in conjunction with a stiff neck suggests the spread of a parameningeal focus of infection into the CNS. New onset of lateralized weakness or numbness, especially if accompanied by a worsening unilateral headache, raises the question of a mass lesion (lymphoma, toxoplasmosis, brain abscess). Monocular visual field disturbances and floaters are characteristic complaints in patients with CMV retinitis. Diplopia and homonymous hemianopsia may indicate a CNS infection or malignancy. Numbness or tingling in the fingers or toes points to a peripheral neuropathy or myelopathy.
Neuropsychiatric difficulties raise the question of HIV-associated dementia. Suggestive symptoms include cognitive problems, difficulty with concentration, memory loss, insomnia, apathy, social isolation, and alterations in mood, especially depression. When accompanied by fever and delirium, they are more likely to be the consequence of an encephalopathy, but such difficulties may also occur as a consequence of a reactive depression. Distinguishing among these conditions can sometimes be difficult and may require neuropsychiatric testing and other diagnostic tests.
Physical Examination
The physical examination is directed toward signs of immunocompromise and its consequences. It includes a careful inspection of the skin, sinuses, eyes, oral cavity, lymph nodes, chest, abdomen, pelvis, and central and peripheral nervous systems. In addition, vital signs should be obtained and carefully recorded. Subtle but persistent unintended weight loss occurs frequently in HIV infection and can be one of the earliest manifestations of disease progression, secondary infection, or malignancy.
Skin
Attention to the skin examination is warranted because skin is a frequently affected organ. Kaposi sarcoma (especially prevalent in gay men), warts, molluscum contagiosum, psoriasis, seborrheic dermatitis, and fungal infections of the skin and nails are especially common. A painless, persistent, raised purple lesion, especially if there is more than one such lesion, may be Kaposi sarcoma and warrants biopsy. Severe facial seborrhea, scars from recurrent herpetic infections, and premature graying are among the subtler signs of immunocompromise.
Head, Eyes, Ears, Nose, and Throat
The sinuses are noted for tenderness, failure to transilluminate, and purulent discharge. Fundoscopic examination may reveal retinal exudates, hemorrhages, or cotton-wool spots suggestive of CMV infection. The exudate is typically pale and with associated hemorrhage; it usually begins peripherally and may be difficult to visualize during routine funduscopic examination.
Careful examination of the oral cavity is essential, looking for signs of oral hairy leukoplakia, thrush, mucosal petechiae, stomatitis, gingivitis, and Kaposi sarcoma. Thrush is an important indicator of disease progression. The most common form is pseudomembranous candidiasis, removable white plaques on any oral mucosal surface. Atrophic oral candidiasis appears as smooth, red patches on the hard or soft palate, buccal mucosa, or dorsal surface of the tongue. These may be easily missed without careful inspection. Rarely, candidiasis can occur in a leukoplakia-like form consisting of white lesions that cannot be wiped off but regress with prolonged antifungal therapy. This form of Candida infection can easily be confused with oral hairy leukoplakia and is distinguished primarily by its response to therapy (biopsy is rarely warranted). Angular cheilitis caused by Candida can appear as erythema, cracks, and fissures at the corner of the mouth. This may require the addition of a topical antifungal cream for adequate treatment. Mucosal petechiae can be the sole evidence of HIV-associated thrombocytopenia. Kaposi sarcoma often produces oral lesions on the hard and soft palate and gingiva. Aphthous stomatitis may be easily confused with stomatitis due to herpes simplex or CMV infections. Biopsy may be required to distinguish them. Lymphoma may appear as a mass or ulcer(s), most commonly seen in the peritonsillar region.
Lymph Nodes
Periodic examination is indicated because adenopathy may be an important sign of disease progression. If lymphadenopathy occurs in two or more noncontiguous extrainguinal sites, persists for longer than 3 months, and no cause other than HIV can be found, it is referred to as persistent generalized lymphadenopathy (PGL). Occasionally, splenomegaly may be found in association with PGL. Asymmetric, large, firm, tender nodes may be evidence of malignancy or secondary infection and often require biopsy.
Chest, Abdomen, Rectum, and Genitalia
The lungs are examined for signs of consolidation, pleural inflammation, and effusion. The heart is checked for murmurs and rubs. The abdomen is noted for enlargement of the liver or spleen and for localized tenderness. Genital and rectal examinations are essential in all patients. A Papanicolaou test should be performed at initial visit, at 6 months, and then annually unless abnormal. Consideration should be given to performing anal Papanicolaou testing in both men and women. Lymphoma, squamous cell carcinoma, CMV infection, and acyclovirresistant herpes simplex infections are examples of unresponsive anorectal lesions that may require biopsy for diagnosis. Anoscopy or sigmoidoscopy may be necessary to diagnose rectal or colonic lesions or diarrhea. Evidence suggests that the risk of anal cancer in MSM is approximately 80 times that of the general population. Like cervical cancer, anal cancer is strongly associated with human papillomavirus infection. Screening for anal cancer using anal brushings (anal Pap smear) has been advocated by some experts. Annual visual inspection and digital rectal exam are recommended. An anal Pap should be considered on an annual basis. If a cervical or anal Papanicolaou test shows atypical squamous cells of undetermined significance or dysplasia of any grade, colposcopy should be performed.
Neurologic Examination
One should check regularly for meningeal irritation, focal neurologic deficits, and changes in mental status. Evidence for peripheral neuropathy, myelopathy, and myopathy should be sought because these are common and often treatable abnormalities. A detailed mental status examination may aid in the early detection of HIV-associated dementia.
Laboratory Testing
Laboratory testing plays an essential role, not only in workup and monitoring but also in deciding on the nature and timing of therapy (Table 13-1). Testing is used to identify those patients who might benefit from special interventions (e.g., hepatitis B vaccine for those who are negative for both hepatitis B surface antibody and hepatitis B core antibody). In other instances, it may reveal hidden medical problems that can be treated (e.g., interferon-α for the treatment of chronic hepatitis C infection). Decisions regarding the initiation of ART and Pneumocystis carinii pneumonia (PCP) prophylaxis are largely based on laboratory tests, especially the CD4 cell count (see Management). Increasingly, the effectiveness of ART is being measured by CD4 cell count and HIV viral load.
Initial Testing of the HIV-Seropositive Patient
Complete blood count and platelet count are essential. Anemia of chronic disease, lymphopenia, and thrombocytopenia are common among HIV-infected patients, especially those patients with advanced disease. Idiopathic thrombocytopenia is sometimes seen in the acute phase of HIV infection. Macrocytic anemia occurs in patients receiving certain reverse transcriptase inhibitors. Marrow suppression with pancytopenia may develop in the context of invasion by lymphoma or disseminated fungal infection. Proper workup may require measurement of serum iron, ferritin, folate, and vitamin B12 concentrations (see Chapter 79). When assessing the cause of anemia, it should be recognized that the measurement of mean corpuscular volume may be confounded by the macrocytosis that commonly occurs when patients are taking zidovudine and stavudine.
Serum chemistries (electrolytes, blood urea nitrogen, creatinine, transaminase, alkaline phosphatase) are indicated as baseline studies before initiating any drug therapies in order to facilitate detection of drug toxicities and comorbid conditions such as HIV- or drug-related renal insufficiency and liver damage due to alcohol or viral hepatitis.
Serologic testing for syphilis is essential because of its high prevalence among HIV-infected individuals. False-positive tests are not uncommon and can be excluded with a confirmatory fluorescent treponemal antibody-absorption test. The natural history of syphilis may be altered by HIV infection, and therefore careful attention to a history and prior treatment for syphilis is essential. If a history of syphilis cannot be documented or if a positive result is accompanied by neurologic signs or symptoms, further workup including a lumbar puncture is advocated by many authorities (see Chapters 124 and 141). Patients who experience therapeutic failure or who cannot receive standard therapy with benzathine penicillin should undergo lumbar puncture also. Interpretation of cerebrospinal fluid (CSF) results may be difficult, however. CSF Venereal Disease Research Laboratory testing is insensitive, and the mononuclear pleocytosis and elevated CSF protein are frequently elevated in HIV infection without neurosyphilis.
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