Acute Respiratory Failure Following HAART Introduction in Patients Treated for Pneumocystis carinii Pneumonia

Abstract

Cases of paradoxical worsening of opportunistic infections shortly after the beginning of highly active antiretroviral therapy (HAART) prompted questions on the optimal timing of introduction of HAART in patients with inaugural AIDS-related opportunistic infections. We describe three cases of acute respiratory failure after early introduction of HAART in patients treated for Pneumocystis carinii pneumonia (PCP). The three patients had severe PCP that initially improved with anti-PCP and adjunctive steroid therapy. HAART was introduced 1 to 16 d after diagnosis of PCP, and steroids were stopped on Day 15. Seven to 17 d after HAART introduction, the three patients developed a second episode of severe acute respiratory failure with high-grade fever and patchy alveolar opacities on the chest roentgenogram. PCP resistant to cotrimoxazole, pulmonary superinfection, and drug-related pneumonitis were suspected but subsequently ruled out. Bronchoalveolar lavage and lung pathologic findings showed severe nonspecific pulmonary inflammatory foci surrounding a few persistent P. carinii cysts. All three patients recovered after HAART interruption or steroid reintroduction. We conclude that acute respiratory failure can recur after initiation of antiretroviral therapy in patients being treated for severe PCP. This phenomenon could result from rapid pulmonary recruitment of fully competent immune and inflammatory cells responding to a few persistent P. carinii cysts. A short course of steroid therapy may suppress this reaction.

Simian Immunodeficiency Virus Infection Alters Chemokine Networks in Lung Tissues of Cynomolgus Macaques

“…It has also been reported that there is paradoxical worsening of PCP in patients started on highly active antiretroviral therapy. 54 Clinical and experimental studies have shown that inflammatory injury is a major cause of morbidity and mortality associated with PCP, potentially due to a more robust immune response to pulmonary microorganisms. We found that immune dysregulation triggered by SIV and P. carinii, and increased expression of IFN-␥, and CXCR3 and CCR5 ligands are associated with these inflammatory responses.…”

Italian Consensus Statement on Management of HIV-Infected Individuals with Advanced Disease Naïve to Antiretroviral Therapy

“…Thus, in patients with PCP, cART needs to be started before completion of the acute phase of anti-P. jiroveci treatment to avoid any possible complication of the clinical picture [52] (B-III). It is important that if there is either evidence of clinical worsening or a lack of response to etiologic treatment, cART should be started during the first 14 days (C-III).…”

CD8 T Cells Modulate CD4 T-Cell and Eosinophil-Mediated Pulmonary Pathology in Pneumocystis Pneumonia in B-Cell-Deficient Mice

“…11,12 These types of interactions may be relevant in immune reconstitution disease (IRD), which occurs in some AIDS patients in whom highly active anti-retroviral therapy results in markedly increased levels of CD4 lymphocytes. In some of these individuals, intense inflammatory responses can occur in the lungs (involving CD4 cells and residual Pneumocystis organisms 13,14 ) and requires vigorous therapeutic intervention. This clinical syndrome highlights the potential interaction of multiple inflammatory cell types and mechanisms that may be involved in the pathology of PCP.…”