HIV Infection and AIDS: Clinical Manifestations

Clinical Manifestations

Treatment of specific manifestations of HIV infection and AIDS in the person with advanced disease targets specific symptoms.

Patients with HIV/AIDS experience a number of symptoms related to the disease as well as the effects of treatment. Nurses need to understand the causes, signs and symptoms, and inter-ventions to enhance the quality of life of patients with HIV across the illness trajectory (Ropka & Williams, 1998; Sherman, 1999). The clinical manifestations of HIV/AIDS are widespread and may affect virtually any organ system. Diseases associated with HIV infection and AIDS result from infections, malignancies, or the direct effect of HIV on body tissues. Symptom assessment tools developed for research purposes could be useful in clinical practice to assess symptom intensity and severity (Holzemer, Henry, Nokes, et al., 1999; Nokes, Wheeler & Kendrew, 1994; Nokes & Bakken, 2002).

RESPIRATORY MANIFESTATIONS

Shortness of breath, dyspnea (labored breathing), cough, chest pain, and fever are associated with various OIs, such as those caused by Pneumocystis carinii, Mycobacterium avium-intracellulare, CMV, and Legionella species. The most common infection in people with AIDS is Pneumocystis carinii pneumonia (PCP), one of the first OIs described in association with AIDS.

PCP. PCP is the most common OI resulting in an AIDS diagnosis.Without prophylactic therapy (discussed below), PCP will de-velop in 80% of all HIV-infected individuals. P. carinii was orig-inally classified as a protozoan; however, studies and analysis of its ribosomal RNA structure suggest that it is a fungus. Its structure and antimicrobial sensitivity are very different from other disease-causing fungi. P. carinii causes disease only in immunocompro-mised hosts, invading and proliferating within the pulmonary alveoli with resultant consolidation of the pulmonary parenchyma.

The clinical presentation of PCP in HIV infection is generally less acute than in people who are immunosuppressed as a result of other conditions. The time between the onset of symptoms and the actual documentation of disease may be weeks to months. Patients with AIDS initially develop nonspecific signs and symp-toms, such as nonproductive cough, fever, chills, shortness of breath, dyspnea, and occasionally chest pain. PCP may be pres-ent despite the absence of crackles. Arterial oxygen concentrations in patients breathing room air may be mildly decreased, indicat-ing minimal hypoxemia.

Untreated, PCP eventually progresses and causes significant pul-monary impairment and, ultimately, respiratory failure. A few pa-tients have a dramatic onset and fulminant course involving severe hypoxemia, cyanosis, tachypnea, and altered mental status. Respi-ratory failure can develop within 2 to 3 days of initial symptoms.

PCP can be diagnosed definitively by identifying the organ-ism in lung tissue or bronchial secretions. This is accomplished by such procedures as sputum induction, bronchial-alveolar lavage, and transbronchial biopsy (by fiberoptic bronchoscopy).

Mycobacterium avium Complex. 

Mycobacterium avium com-plex (MAC) disease is a leading OI in people with AIDS. Or-ganisms belonging to MAC include M. avium, M. intracellulare, and M. scrofulaceum. MAC, comprising a group of acid-fast bacilli, usually causes respiratory infection but is also commonly found in the GI tract, lymph nodes, and bone marrow. Most patients with AIDS who have T-cell counts less than 100 have widespread disease at diagnosis and are usually debilitated. MAC infections are associated with rising mortality rates.

Tuberculosis. 

Mycobacterium tuberculosistends to occur in in-jection drug users and other groups with a preexisting high preva-lence of tuberculosis (TB) infection. Unlike other OIs, TB tends to occur early in the course of HIV infection, usually preceding the diagnosis of AIDS. This early occurrence is associated with the development of caseating granulomas (dry, cheeselike masses of granulation tissue), which should raise the suspicion of TB. At this stage, TB responds well to antituberculosis therapy.

TB that occurs late in HIV infection is characterized by ab-sence of an immune response to a tuberculin skin test response.

This is known as anergy and results because the compromised immune system can no longer respond to the TB antigen. In the later stages of HIV infection, TB is associated with dissemination to extrapulmonary sites such as the CNS, bone, pericardium, stomach, peritoneum, and scrotum. Multiple drug-resistant strains of the bacillus have emerged and are often associated with non-compliance with antituberculosis therapy.

GI MANIFESTATIONS

The GI manifestations of AIDS include loss of appetite, nausea, vomiting, oral and esophageal candidiasis, and chronic diarrhea. Diarrhea is a problem in 50% to 90% of all AIDS patients. GI symptoms may be related to the direct effect of HIV on the cells lining the intestines. Some of the enteric pathogens that occur most frequently, identified by stool cultures or intestinal biopsy, include Cryptosporidium muris, Salmonella species, Isopora belli,Giardia lamblia, CMV, Clostridium difficile, and M. avium-intracellulare. In patients with AIDS, the effects of diarrhea can bedevastating in terms of profound weight loss (more than 10% of body weight), fluid and electrolyte imbalances, perianal skin ex-coriation, weakness, and inability to perform the usual activities of daily living.

Oral Candidiasis. 

Candidiasis, a fungal infection, occurs in nearlyall patients with AIDS and AIDS-related conditions. Commonly preceding other life-threatening infections, it is characterized by creamy-white patches in the oral cavity. Untreated, oral can-didiasis progresses to involve the esophagus and stomach. Asso-ciated signs and symptoms include difficult and painful swallowing and retrosternal pain. Some patients also develop ulcerating oral lesions and are particularly susceptible to dissemination of can-didiasis to other body systems.

Wasting Syndrome. 

Wasting syndromeis part of the categoryC case definition for AIDS. Diagnostic criteria include profound involuntary weight loss exceeding 10% of baseline body weight and either chronic diarrhea for more than 30 days or chronic weakness and documented intermittent or constant fever in the absence of any concurrent illness that could explain these find-ings. This protein-energy malnutrition is multifactorial. In some AIDS-associated illnesses, patients experience a hypermetabolic state in which excessive calories are burned and lean body mass is lost. This state is similar to that seen in sepsis and trauma and can lead to organ failure. A distinction between cachexia (wasting) and malnutrition or between cachexia and simple weight loss is important because the metabolic derangement seen in wasting syndrome may not be modified by nutritional support alone.

Anorexia, diarrhea, GI malabsorption, and lack of nutrition in chronic disease all contribute to wasting syndrome. Progressive tissue wasting, however, may occur with only modest GI involve-ment and without diarrhea. Tumor necrosis factor (TNF) and interleukin-1 (IL-1) are cytokines that play important roles in AIDS-related wasting syndrome. Both act directly on the hypo-thalamus to cause anorexia. Cytokine-induced fever accelerates the body’s metabolism by 14% for every 1°F increase in temper-ature. TNF causes inefficient use of lipids by reducing enzymes that are needed for fat metabolism, whereas IL-1 triggers the re-lease of amino acids from muscle tissue. People with AIDS gen-erally experience increased protein metabolism in relation to fat metabolism, which results in significant decreases in lean body mass due to muscle and protein breakdown.

Hypertriglyceridemia, seen in people with AIDS and attrib-uted to chronically elevated cytokine levels, can persist in peoplewith AIDS for months without tissue wasting and loss of lean body mass. It is believed that infections and sepsis lead to tran-sient rises in TNF, IL-1, and other cell mediators above the chronically elevated levels generally seen. These transient rises in TNF and IL-1 trigger muscle wasting.

ONCOLOGIC MANIFESTATIONS

Patients with AIDS have a higher than usual incidence of cancer, possibly related to HIV stimulation of developing cancer cells or to the immune deficiency allowing cancer-causing substances, such as viruses, to transform susceptible cells into malignant cells. Kaposi’s sarcoma, certain types of B-cell lymphomas, and inva-sive cervical carcinoma are included in the CDC classification of AIDS-related malignancies. Carcinomas of the skin, stomach, pancreas, rectum, and bladder also occur more frequently than expected in people with AIDS.

Kaposi’s Sarcoma. 

Kaposi’s sarcoma(KS), the most commonHIV-related malignancy, is a disease involving the endothelial layer of blood and lymphatic vessels. It is associated with human herpes virus 8 (HHV-8) transmission (USPHS/IDSA, 2002). When first noted in 1872 by Dr. Moritz Kaposi, KS characteris-tically presented as lower-extremity skin lesions in elderly men of Eastern European ancestry. This form, referred to as classic Ka-posi’s sarcoma, was slow to progress and easily treated. An en-demic form of KS, found in children and young men in equatorial Africa, is more virulent than the classic form. Acquired KS occurs in patients who are treated with immunosuppressive agents and commonly occurs in patients who have undergone organ trans-plantation. In such patients, acquired KS usually resolves once the dose of the immunosuppressive medication is decreased or discontinued. In people with AIDS, epidemic KS is most often seen in male homosexuals and bisexuals.

Although the histopathology of all forms of KS is virtually identical, the clinical manifestations differ: AIDS-related KS ex-hibits a more variable and aggressive course, ranging from local-ized cutaneous lesions to disseminated disease involving multiple organ systems. Cutaneous signs may be the first manifestations of HIV, appearing in more than 90% of HIV-infected patients as immune function deteriorates. These skin signs correlate to low CD4 counts. Some disorders, such as Kaposi’s sarcoma, oral hairy leukoplakia, facial molluscum contagiosum, dry skin, and oral candidiasis, indicate CD4 counts at or below 200 to 300.

Cutaneous lesions appearing anywhere on the body are usu-ally brownish pink to deep purple. They may be flat or raised and surrounded by ecchymoses (hemorrhagic patches) and edema (Fig. 52-3). Rapid development of lesions involving large areas of skin is associated with extensive disfigurement. The location and size of some lesions can lead to venous stasis, lymphedema, and pain. Ulcerative lesions disrupt skin integrity and increase dis-comfort and susceptibility to infection. The most common sites of visceral involvement include the lymph nodes, GI tract, and lungs. Involvement of internal organs may eventually lead to organ failure, hemorrhage, infection, and death.

Diagnosis of KS is confirmed by biopsy of suspected lesions. Prognosis depends on the extent of the tumor, presence of con-stitutional symptoms, and CD4 count. Death may result from tumor progression. More often, however, it results from other complications of HIV infection.

B-Cell Lymphomas. 

B-cell lymphomasare the second mostcommon malignancy occurring in people with AIDS. Lym-phomas associated with AIDS usually differ from those occurring in the general population. 

Patients with AIDS are generally much younger than the usual population affected by non-Hodgkin’s lymphoma. In addition, AIDS-related lymphomas tend to de-velop outside the lymph nodes, most commonly in the brain, bone marrow, and GI tract. These types of lymphomas are char-acteristically of a higher grade, indicating aggressive growth and resistance to treatment. The course of AIDS-related lymphomas includes multiple sites of organ involvement and complications related to OIs. Although aggressive combination chemotherapy is frequently successful in non-Hodgkin’s lymphoma not associ-ated with HIV infection, it is less successful in people with AIDS because of the severe hematologic toxicity and complications of OIs that occur from treatment.

NEUROLOGIC MANIFESTATIONS

An estimated 80% of all patients with AIDS experience some form of neurologic involvement during the course of HIV infec-tion. Many neuropathologic disorders are underreported because patients may have neurologic involvement without overt signs or symptoms. Neurologic complications involve central, peripheral, and autonomic functions.

Neurologic dysfunction results from the direct effects of HIV on nervous system tissue, OIs, primary or metastatic neoplasms, cerebrovascular changes, metabolic encephalopathies, or compli-cations secondary to therapy. Immune system response to HIV infection in the CNS includes inflammation, atrophy, demyeli-nation, degeneration, and necrosis.

HIV Encephalopathy. 

HIV encephalopathywas formerly re-ferred to as AIDS dementia complex. It is a clinical syndrome characterized by a progressive decline in cognitive, behavioral, and motor functions. Substantial evidence exists that HIV en-cephalopathy is a direct result of HIV infection. HIV has been found in the brain and cerebrospinal fluid (CSF) of patients with HIV encephalopathy. The brain cells infected by HIV are pre-dominantly the CD4 cells of monocyte-macrophage lineage. HIV infection is thought to trigger the release of toxins or lym-phokines that result in cellular dysfunction or interference with neurotransmitter function rather than cellular damage.

Signs and symptoms may be subtle and difficult to distinguish from fatigue, depression, or the adverse effects of treatment for infections and malignancies. Early manifestations include mem-ory deficits, headache, difficulty concentrating, progressive con-fusion, psychomotor slowing, apathy, and ataxia. Later stages include global cognitive impairments, delay in verbal responses, a vacant stare, spastic paraparesis, hyperreflexia, psychosis, hallu-cinations, tremor, incontinence, seizures, mutism, and death.

Confirming the diagnosis of HIV encephalopathy may be dif-ficult. Extensive neurologic evaluation includes a computed to-mography (CT) scan, which may indicate diffuse cerebral atrophy and ventricular enlargement. Other tests that may detect abnor-malities include magnetic resonance imaging (MRI), analysis of CSF through lumbar puncture, and brain biopsy.

Cryptococcus neoformans. 

A fungal infection,Cryptococcus neo-formans, is another common OI among patients with AIDS andcauses neurologic disease. Cryptococcal meningitis is character-ized by symptoms such as fever, headache, malaise, stiff neck, nausea, vomiting, mental status changes, and seizures. Diagnosis is confirmed by CSF analysis.

Progressive Multifocal Leukoencephalopathy. 

Progressive multi-focal leukoencephalopathy is a demyelinating CNS disorder that affects the oligodendroglia. It occurs in about 3% of AIDS pa-tients. Clinical manifestations often begin with mental confusion and rapidly progress to include blindness, aphasia, paresis (slight paralysis), and death. Treatments have greatly reduced the threat of mortality associated with this disorder.

Other Neurologic Disorders. 

Other common infections involv-ing the nervous system include Toxoplasma gondii, CMV, and M. tuberculosis. Additional neurologic manifestations includeboth central and peripheral neuropathies. Vascular myelopathy is a degenerative disorder affecting the lateral and posterior columns of the spinal cord, resulting in progressive spastic paraparesis, ataxia, and incontinence. HIV-related peripheral neuropathy is thought to be a demyelinating disorder; it is associated with pain and numbness in the extremities, weakness, diminished deep ten-don reflexes, orthostatic hypotension, and impotence.

DEPRESSIVE MANIFESTATIONS

The prevalence of depression among people with HIV infection is unknown. The causes of depression are multifactorial and may include a history of preexisting mental illness, neuropsychiatric disturbances, and psychosocial factors. Depression also occurs in people with HIV infection in response to the physical symptoms, including pain and weight loss, and the lack of someone to talk with about their concerns. People with HIV/AIDS who are de-pressed may experience irrational guilt and shame, loss of self-esteem, feelings of helplessness and worthlessness, and suicidal ideation.

INTEGUMENTARY MANIFESTATIONS

Cutaneous manifestations are associated with HIV infection and the accompanying OIs and malignancies. KS (described above) and OIs such as herpes zoster and herpes simplex are associated with painful vesicles that disrupt skin integrity. Molluscum con-tagiosum is a viral infection characterized by deforming plaqueformation. Seborrheic dermatitis is associated with an indurated, diffuse, scaly rash involving the scalp and face. Patients with AIDS may also exhibit a generalized folliculitis associated with dry, flaking skin or atopic dermatitis, such as eczema or psoriasis. Up to 60% of patients treated with trimethoprim-sulfamethoxazole (TMP-SMZ) develop a drug-related rash that is pruritic with pinkish-red macules and papules. Regardless of the origin of these rashes, patients experience discomfort and are at increased risk for additional infection from disrupted skin integrity.

ENDOCRINE MANIFESTATIONS

The endocrine manifestations of HIV infection are not com-pletely understood. At autopsy, endocrine glands show infiltra-tion and destruction from OIs or neoplasms. Endocrine function may also be affected by therapeutic agents.

GYNECOLOGIC MANIFESTATIONS

Persistent, recurrent vaginal candidiasis may be the first sign of HIV infection in women. Past or present genital ulcer disease is a risk factor for the transmission of HIV infection. Women with HIV infection are more susceptible to and have increased rates and recurrence of genital ulcer disease and venereal warts. Ulcer-ative STDs such as chancroid, syphilis, and herpes are more se-vere in women with HIV infection. Human papillomavirus causes venereal warts and is a risk factor for cervical intraepithe-lial neoplasia, a cellular change that is frequently a precursor to cervical cancer. Women with HIV are 10 times more likely to de-velop cervical intraepithelial neoplasia than are those not infected with HIV. There is a strong association between abnormal Pap smears and HIV seropositivity. HIV-seropositive women with cervical carcinoma present with a more advanced stage of disease and have more persistent and recurrent disease and a shorter in-terval to recurrence and death than women who do not have HIV infection.

A significant percentage of women who require hospitalization for pelvic inflammatory disease (PID) have HIV infection. Women with HIV are at increased risk for PID, and the inflammation as-sociated with PID may potentiate the transmission of HIV in-fection. Moreover, women with HIV appear to have a higher incidence of menstrual abnormalities, including amenorrhea or bleeding between periods, than women without HIV infection. The failure of health care providers to consider HIV infection in women may lead to a later diagnosis, thereby denying women appropriate treatment.

Gerontologic Considerations

More than 10% of all AIDS cases in the United States have occurred in people aged 50 years or older. HIV infection in middle-aged and older populations may be underreported and under-diagnosed because health care professionals erroneously believe they are not at risk for HIV infection. Many older adults are sexually active but do not use condoms, viewing them only as a means of unneeded birth control and not considering themselves at risk for HIV infection. Many older gay men who grew up and lived in an era when disclosure of their sexual orientation was not acceptable have lost long-time partners and may turn to younger males for sexual gratification. Older adults may also be injection drug users or may have received HIV-infected blood through transfusions before 1985. As a result, they may be at risk for HIV infection.

Normal age-related changes include a reduction in immune system function similar to that of HIV infection. Older adults are normally at greater risk for infections, cancer, and autoimmune disorders. Many older adults also experience the loss of loved ones, resulting in depression and bereavement, factors that are also associated with depressed immune function. HIV-related de-mentia in the older adult may mimic Alzheimer’s disease and may be misdiagnosed. There are at least three major differences between older (age 50 and up) and younger persons with HIV/ AIDS: presence of comorbidities such as diabetes or high blood pressure; number of persons to whom HIV status was disclosed; and physical functioning ability (Nokes et al., 2000).