27th June 2023

Respiratory complications in HIV/ AIDS

Pneumocystis jirovecii pneumonia

Pneumocystis jirovecii (previously Pneumocystis carinii (PCP)) is an airborne transmitted unicellular fungus characteristically infecting immunocompromised patients. In HIV, P. jirovecii infection typically indicates a CD4+ T-cell count is <200/μL, whereas it is often asymptomatic in immunocompetent individuals.

P. jirovecii presents with fever, dry cough, recurrent bacterial pneumonia, and dyspnoea, sometimes with oral candidiasis and weight loss. P. jirovecii may be insidious in HIV, with symptoms over weeks prior to presentation. Auscultation may demonstrate crackles but may be normal. Chest radiography and high-resolution CT may demonstrate bilateral pulmonary interstitial infiltrates, ground-glass opacity, and pneumatoceles (cysts). Pneumocystis is not easily cultured, necessitating microscopic staining, polymerase chain reaction (PCR) or loop-mediated isothermal amplification (LAMP) testing. Broncho-alveolar lavage and induced sputum are used, whereas spontaneously produced sputum has lower sensitivity. β-D-glucan, which is found in cell walls of Pneumocystis, and some other fungi, can screen for possible Pneumocystis infection but is non-specific.

Management for P. jirovecii usually involves co-trimoxazole for 21 days, however, there is some resistance. Co-trimoxazole is also used in prophylaxis for P. jirovecii in patients with a CD4+ T cell count <200 cells/μL. Lower CD4+ T-cells indicate a poorer prognosis. Mortality is ~10% in hospitalised patients.

Reactivation tuberculosis

HIV-associated immunosuppression accelerates tuberculosis progression, either via primary infection or reactivation of latent infection, and TB accelerates CD4+ T cell loss, thereby accelerating HIV, i.e. TB and HIV both increase the rate of progression of the other disease. Patients started on antiretroviral therapy after AIDS may develop immune reconstitution inflammatory syndrome (IRIS), which is worse with TB. Immune reconstitution causes inflammation, with recurrence of TB symptoms, abscess formation and lymphadenopathy. Neurological involvement can lead to death. Clinical presentations in pulmonary TB may include haemoptysis and features of pneumonia.

More immunocompromised patients will often have less typical features of pulmonary TB:

• Lower lobe involvement
• Tuberculous pneumonia
• Miliary TB
• Hilar/ mediastinal lymphadenopathy

TB in HIV has lower bacillary loads in sputum, meaning traditional staining is infrequently positive. Tuberculin skin testing is less frequently positive in patients with lower CD4+ T-cell counts, which requires a functional Th1 cytokine response. Broncho-alveolar lavage or bronchial biopsy may therefore be needed. Cavitation is less likely, with more isolated extrapulmonary disease. TB treatment in HIV is the same as if seronegative-rifampicin, isoniazid, pyrazinamide, and ethambutol are given for two months, followed by four months of rifampicin and isoniazid. HIV infection increases the risk of adverse events associated with anti-tuberculosis medications, including:

• Skin reactions
• Drug-induced liver injury
• Peripheral neuropathy with isoniazid (pyridoxine prophylaxis is given)
• Drug interactions with antiretroviral therapy

Rifampicin strongly induces cytochrome P450 3A4, therefore, rifabutin is recommended instead in patients taking non-nucleoside reverse transcriptase inhibitors or protease inhibitors. In treatment-naïve patients, the priority is the treatment of TB before highly active antiretroviral therapy (HAART) is initiated.

Pneumonia

Bacterial pneumonia is the most common cause of infection and admission in HIV. Consequently, patients with reduced CD4+ T-cell counts are recommended to have pneumococcal vaccines. Risk factors for bacterial pneumonia in HIV include:

• Intravenous drug use
• Smoking
• Increasing age
• Lower CD4+ T-cell count

The most common organism in community-acquired pneumonia (CAP) in HIV is Streptococcus pneumoniae, Haemophilus influenzae, Pseudomonas aeruginosa and Staphylococcus aureus are also common. Legionella infection is more common but remains a relatively small proportion of cases. CAP in HIV presents similarly to in seronegative individuals. Chest radiography usually features unilateral consolidation in Streptococcus or Haemophilus infection, or cavitation in Pseudomonas aeruginosa or Staphylococcus aureus. Management is similar, however, macrolides (e.g. clarithromycin) need to be given alongside a beta-lactam rather than alone because of increased resistance in Streptococcus pneumoniae.