42 HIV: respiratory disorders

Respiratory symptoms with a wide disease spectrum are common in HIV infection (Box 42.1). They include processes not directly related to HIV, e.g. bronchogenic carcinoma, smokers’ bronchitis, or IV drug use associated pulmonary vascular disease.

Considerable overlap of symptoms and signs in different conditions and dual infections may occur. Uncommon for a particular constellation of symptoms, clinical findings, and radiological abnormalities to be absolutely diagnostic—a full investigation is always required. However, radiological appearances may suggest different groups of conditions.

As deterioration can sometimes be rapid it is important that ‘best guess’ therapy is initiated while awaiting the results of microbiology.

Before HAART bacterial pneumonia was the most frequent pulmonary complication of HIV, occurring in up to 42% in autopsy studies. An episode of bacterial pneumonia is associated with subsequent ↑ morbidity and ↓ survival time.

Most common pathogens are Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus which occur more frequently in the general population as a cause of pneumonia. In pneumococcal infection rate of bacteraemia is ↑ and there may be ↑ incidence of penicillin-resistant isolates. Intravenous drug use further ↑ the risk of bacterial pneumonia. Less common causes include Rhodococcus equi which produces a cavitatory pneumonia of insidious onset.

Most bacterial pneumonias present acutely with symptoms and radiological patterns similar to that seen in HIV −ve patients (lobar or broncho-pneumonic consolidation). However, the radiological presentation may be indistinguishable from other OIs, and H.influenzae has been reported to present with diffuse opacities mimicking PCP (Table 42.1). As immunodeficiency becomes more advanced, pneumonias due to Staph.aureus and Ps.aeruginosa become more important and may produce cavitation.

In patients presenting with a clinical diagnosis of bacterial pneumonia:

For outpatient and less severe pneumonia oral amoxicillin may suffice and a macrolide may be added if no improvement.

The AIDS indicator disease in ~65% of patients before the initiation of 1° prophylaxis programmes and effective antiretroviral therapy. Initially thought to be protozoan, but genetic analysis indicates that the organism is a unicellular fungus. Infection usually occurs when CD4 counts <200cells/μL or CD4 percentage <15%. Although natural colonization/infection occurs frequently in early life it is thought that clinical pneumonitis represents new infection rather than reactivation of latent organisms.

PCP is almost completely preventable using 1° prophylaxis. The gold standard is co-trimoxazole. Dapsone, dapsone and pyrimethamine, atovaquone, and pentamidine are alternatives ( Chapter 38, p. 442). Cutaneous hypersensitivity reactions to co-trimoxazole are common, but 80% of HIV +ve patients can be desensitized by the use of gradually ↑ doses ( Chapter 38, Table 38.2).

Usually presents sub-acutely with symptoms ↑ over weeks with night sweats, systemic symptoms and weight loss, dry cough, progressive dyspnoea initially on exertion and eventually at rest, occasionally with a spontaneous pneumothorax. Abnormalities on respiratory examination often minimal or absent and significant ↓ of pulmonary function may occur despite minimal chest X-ray changes.

If history is suspicious but normal resting oxygen saturations, exercise oximetry showing ↓ in oxygen saturation by 5% or to <90% is highly suggestive of PCP.

Specific diagnosis requires demonstration of Pneumocystis jiroveci cysts in respiratory secretions or lung tissue. Patients with borderline lung function may require sputum induction and bronchoscopy.

Prior to initiating investigations in those presenting with a history suggestive of PCP, it is essential to assess pulmonary impairment and the need for oxygen supplements by pulse oximetry and arterial blood gases.

►If there is pulmonary impairment, delays in initiating PCP therapy should be kept to a minimum. HAART should be started within 2 weeks of treatment of PCP. Delaying HAART is associated with ↑ AIDS progression and death.

Gold standard antibiotic therapy is co-trimoxazole 120mg/kg in four divided doses daily for 21 days. Haematology, liver function tests, and the skin must be monitored carefully for evidence of toxicity or developing hypersensitivity. Folinic acid supplements may be considered if there is evidence of impaired marrow function. For non-responders or hyper-sensitive patients alternative regimens include clindamycin (600mg four times daily) and primaquine (15–30mg/day), dapsone (100mg/day) and trimethoprim (5mg/kg every 4–6 hours), atovaquone (750mg three times daily), IV pentamidine (600mg/day), and trimetrexate (45mg/m²/day IV plus folinic acid). Caspofungin (70mg/day) in addition to co-trimoxazole has been used successfully in some patients not responding.

In patients with arterial oxygen pressures <9.3kPa steroid therapy is recommended as it ↓ risk of respiratory failure and mortality. Conventional regimen is prednisolone (or equivalent) 40mg twice daily for 5 days, 40mg once daily for 5 days, followed by 20mg daily for 5–10 days. There is no significant ↑ in risk of other OIs except Candida spp and local herpes simplex virus.

Patients with severe PCP may progress to respiratory failure requiring ventilatory support with constant positive airways pressure (CPAP) or intubation and ventilation. Pneumothorax may require chest drain insertion. Adverse prognostic indicators include ↑ serum lactic dehydrogenase (LDH) levels, need for high ventilatory pressures, and prolonged stay in intensive therapy unit (ITU).

Following successful treatment, 2° prophylaxis, with the same regimens as for 1° presentation, should be continued.

On a worldwide scale TB is the most important HIV-associated OI, and as a result the prevalence of TB in the developed world has ↑. In sub-Saharan Africa up to ~65% of patients with extra-pulmonary TB have HIV infection. Patients presenting primarily with TB should have their risk profile for HIV infection assessed and be offered HIV testing as appropriate. Those with known HIV infection and pulmonary disease should have TB excluded. Proven or suspected TB should be notified and contact tracing with assessment initiated.

TB can occur at any stage of HIV infection. Classic presentation of pulmonary TB is night sweats/fever, cough, pleuritic chest pain, haemoptysis, and weight loss. Atypical presentations occur as CD4 count ↓. Lobar distribution of pulmonary infection may mimic community-acquired pneumonia. Disseminated and extra-pulmonary diseases are more common with ↓ CD4 count. Although most cases are caused by reactivation of latent infection, 1° infection with rapid progression to active TB can occur when CD4 counts are <100cells/μL. TB has an additional immunosuppressive effect in HIV infection.

Drug therapy of TB-co-infected HIV +ve patients is complex because of ↑ drug toxicities, drug interactions, and paradoxical reactions. If TB is strongly suspected, empirical therapy with four drugs should be initiated immediately after cultures sent. Even if cultures are negative, a full course may be required if there is clinical response despite negative cultures. Treatment of active TB may lead to ↑ in CD4 counts.

A 6 month short course of anti-TB therapy is sufficient for respiratory disease and most extra-pulmonary TB with fully sensitive organisms. TB meningitis requires 12 months treatment. Treatment should prefer-ably start with quadruple therapy using isoniazid (300mg daily), rifampicin (600mg daily), pyrazinamide (1.5–2g daily), and ethambutol (15mg/kg/day) with standard monitoring precautions until mycobacterial drug sensitiv-ities are known. After 2 months switch to rifampicin and isoniazid for a further 4 months.

If MDRTB suspected seek expert advice on initial regime.

►Check visual acuities prior to starting ethambutol. Monitor visual symptoms and liver function tests regularly.

►There are very important drug–drug interactions between anti-TB and anti-HIV therapies because of their varying enzyme-inducing and enzyme-inhibiting effects ( Table 53.1). Joint management involving physicians experienced in TB and HIV therapy is important. Rifampicin produces across-the-board ↓ in HAART levels. When used in conjunction with rifampicin, efavirenz should be increased to 800mg/day in Caucasians. Evidence suggests that 600mg/day is sufficient in Black Africans or Caucasians <50kg. Protease inhibitors should not be used with rifampicin; rifabutin may be used at a lower dose, i.e. 150mg every other day.

Drug interactions may be minimized as follows.

Pulmonary disease is diagnosed less frequently than meningitis in patients with AIDS although the lung is the most likely portal of entry. Pulmonary involvement can be asymptomatic, but precedes the onset of disseminated disease in the majority of patients. Pulmonary involvement can produce cough, fever, malaise, shortness of breath, and pleuritic pain.

Treating the pulmonary lesion can prevent disseminated disease. Consists of amphotericin B combined with flucytosine as induction therapy, followed by fluconazole or itraconazole.

Aspergillus infections in advanced HIV disease are uncommon and occur in conjunction with other OIs. Invasive disease occurs predominantly in patients with severe neutropenia. In HIV disease the lung is the most important site of invasive aspergillosis. Symptoms include fever, dyspnoea, cough, chest pain, and haemoptysis. ~20% have unilateral or bilateral diffuse or nodular infiltrates.

In patients with severe neutropenia granulocyte macrophage colony stimulating factor may have an adjunctive role.

Patients with PCP often have CMV isolated from bronchial washings or lung biopsy. In most cases this represents viral replication without pneumonitis and the patient responds to PCP therapy alone. Active pneumonitis occurs much less frequently than in patients taking immunosuppressive therapy post transplant. Hypoxia is usual.

Patients with interstitial pneumonia and positive CMV identification in lung tissue should be treated with anti-CMV therapy using ganciclovir or foscarnet ( Chapter 44, Opportunistic infections (OIs) p. 514). A role for CMV immunoglobulin is not proven in the HIV setting.

Patients with HIV-related persistent generalized lymphadenopathy have sub-diaphragmatic lymphadenopathy but do not have significant hilar or mediastinal node enlargement. Hilar or mediastinal adenopathy implies significant pathology. The differential diagnosis includes:

May occasionally be seen in active PCP, but other pulmonary radiological abnormalities will be present. A careful search for peripheral lymphadenopathy, skin lesions, and other abnormalities that could be subjected to histological and microbiological examinations should be sought.

1° pulmonary hypertension can occur as a consequence of HIV infection. IDUs may develop pulmonary small vessel obstruction due to injection of particulate material or may suffer recurrent pulmonary emboli.

Intense fatigue, breathlessness, and faintness on exertion are features of severe pulmonary hypertension. Clinical features of right ventricular hypertrophy include a heave, prominent A wave in the jugular pulse, and a third heart sound. Should be considered in unexplained shortness of breath.

Anticoagulants and pulmonary vasodilators. HAART may improve mortality and morbidity.