Noninfectious Conditions in Patients with Human Immunodeficiency Virus Infection

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Chapter 30 Noninfectious Conditions in Patients with Human Immunodeficiency Virus Infection

Although most complications affecting the lungs during the course of HIV infection arise from the viral infection itself, especially as reported early in the epidemic, HIV-infected patients may present with or subsequently develop complications related to alterations in immune regulation. A marked CD8⁺ T cell infiltrate in the lung may be caused by HIV in both symptomatic and nonsymptomatic patients. The effects of the virus on the pulmonary microenvironment include a progressive decline in local immunocompetence that results in failure to mount a protective immune response against opportunistic infections. The spectrum of noninfectious complications associated with HIV infection encompasses other idiopathic conditions and pulmonary malignancies, which include Kaposi sarcoma, Hodgkin and non-Hodgkin lymphomas, and solid tumors (Table 30-1 and 30-2).

Table 30-1 Noninfectious Pulmonary Conditions Associated With Human Immunodeficiency Virus Type 1 Infection

Disease Category	Specific Disease(s)
Neoplastic disease	Kaposi sarcoma Castleman disease Non-Hodgkin lymphoma Primary effusion lymphoma Lung cancer
Inflammatory disease	Nonspecific interstitial pneumonitis Lymphocytic interstitial pneumonitis Lung fibrosis
Airway disease	Chronic obstructive pulmonary disease Emphysema
Pulmonary vascular disease	Pulmonary hypertension
Miscellaneous	Antiretroviral treatment–induced respiratory disease

Table 30-2 Association of Noninfectious Pulmonary Conditions with Degree of Immunodeficiency

Degree of Immunodeficiency	Noninfectious Pulmonary Condition
Severe (CD4⁺ cell count less than 50 cells/µL)	Kaposi sarcoma Castleman disease Non-Hodgkin lymphoma Primary effusion lymphoma Lung cancer Nonspecific interstitial pneumonitis Lymphocytic interstitial pneumonitis Chronic obstructive pulmonary disease Pulmonary hypertension Antiretroviral treatment–induced respiratory disease
Moderate to severe (CD4⁺ cell count 50-200 cells/µL)	Kaposi sarcoma Non-Hodgkin lymphoma Lung cancer Nonspecific interstitial pneumonitis Lymphocytic interstitial pneumonitis Chronic obstructive pulmonary disease Pulmonary hypertension Antiretroviral treatment–induced respiratory disease
Moderate (CD4⁺ cell count 200-350 cells/µL)	Non-Hodgkin lymphoma Lung cancer Chronic obstructive pulmonary disease Pulmonary hypertension Antiretroviral treatment–induced respiratory disease
Normal (CD4⁺ cell count greater than 350 cells/µL)	Lung cancer Chronic obstructive pulmonary disease Pulmonary hypertension

Respiratory Symptoms and Pulmonary Function

Respiratory symptoms, impaired diffusion, emphysema, airway obstruction, and small airway disease related to HIV infection are common clinical findings. In a recent study of 167 HIV-1–infected persons, nearly two thirds were found to have diffusion impairment and one fifth had irreversible airway obstruction. The most common symptoms and signs were dyspnea and a cough. Severe symptoms such as shortness of breath at rest were less frequent. Patients with respiratory symptoms were more likely to be current or past injection drug users and smokers. Approximately one fourth reported using respiratory inhaler medication. Smoking and the number of pack-years smoked increased the risk of diffusion impairment and airway obstruction. Prophylaxis for Pneumocystis jirovecii pneumonia and low CD4⁺ cell counts increased the risk for impaired diffusion, and treatment with cART increased the risk for airway obstruction. These associations may be a proxy for the duration of HIV-1 infection and severity of the underlying immunodeficiency. The correlation with low CD4⁺ cell counts supports this possibility. Overall, the HIV-infected population appears to be more susceptible to noninfectious disease for a number of reasons. Smoking cessation counseling certainly offers one possibility of reducing the increased susceptibility.

Neoplasia

Cancer incidence is higher in persons with immunodeficiency of all causes. In HIV-1 infection, cancers that are uncommon in the general population predominate and include mainly lymphoma and Kaposi sarcoma. Other, more common cancers are now seen with increasing frequency; however, as HIV-1 infection has become controllable with antiretrovirals.

Kaposi Sarcoma

(C, Courtesy Dr. L. Huang. D, Courtesy Dr. J. Junge.)

Pulmonary Kaposi sarcoma is highly likely in a HIV-1–infected person with a CD4⁺ cell count of less than 100/µL, the characteristic cutaneous or mucocutaneous lesions, and pulmonary symptoms. Bronchoscopy is useful to visualize typical endobronchial lesions (see Figure 30-1, C). These are flat or slightly raised and occur throughout the tracheobronchial tree but are seen most frequently at airway bifurcations. Pleural effusions usually are exudative and may be serous or serosanguineous. Serum lactate dehydrogenase may be elevated. Histologic verification is usually not required for a diagnosis of Kaposi sarcoma. Endobronchial biopsy may confer a substantial risk of severe bleeding, but biopsy may be necessary in cases in which bronchial involvement is lacking. In such cases, transbronchial or percutaneous needle biopsy is useful. In cases of pleural Kaposi sarcoma, video-assisted thoracoscopy can be used to visualize pleural lesions and to perform biopsy. Open lung biopsy in this setting is obsolete because of the associated complications. Lung biopsy specimens show typical features of Kaposi sarcoma, which include a tumor-like infiltrate with a peribronchovascular distribution of spindle cells. Slitlike spaces without endothelium contain extravasated erythrocytes (see Figure 30-1, D). In situ hybridization and immunostaining usually are positive for HHV-8. HHV-8 DNA is detectable in bronchoalveolar lavage fluid (BAL) cells.