© 2002 American Thoracic Society
Transient clinical deterioration in hiv patients with Pneumocystis carinii Pneumonia after starting highly active antiretroviral therapyAnother case of immune restoration inflammatory syndromeTo the Editor :We read with interest the article by Wislez and colleagues (1) describing the clinical deterioration of three patients who had initiated highly active antiretroviral therapy (HAART) early, after the diagnosis of Pneumocystis carinii pneumonia (PCP). We also observed a transient clinical deterioration in three patients with confirmed PCP soon after the introduction of HAART. These cases were diagnosed between May 1999 and October 2000, during which time there were 16 confirmed cases of PCP in total. All three presented with advanced HIV disease (median CD4 26 cells/mm3, mean log10 viral load 5.5). Despite severe disease, significant clinical and radiological improvement was observed by day 12–15 after administration of parenteral cotrimoxazole and high dose oral steroids. HAART was introduced within 15–18 days of PCP diagnosis. A median of 5 days later (range 3–17), all patients experienced acute respiratory failure accompanied by swinging fever and deterioration of the chest radiograph. Bronchoalveolar lavage revealed P. carinii cysts only. Further investigations did not reveal additional pathogens. Clinical recovery was observed on reintroducing high dose steroids and alternative PCP therapy. Two weeks after initiating HAART, the median CD4 count was 62 cells/mm3 (range 14–82). The log10 viral load had fallen to 2.87. All patients made a full recovery by 29–40 days after PCP diagnosis. These cases bear close similarity to those described by Wislez and coworkers. After initiation of HAART, rapid improvement in host immune responses result in inflammatory reactions at established infection sites. Such paradoxical inflammatory responses are well described in HIV-related tuberculosis (2, 3), cytomegalovirus infection (4), and cryptococcosis (5); however, these have rarely been described in PCP, a common HIV-related opportunistic infection. In patients coinfected with HIV/TB cases experiencing paradoxical responses had larger drops in viral load compared with patients who remained well (3). All three patients in this report demonstrated significant decreases in viral load at 2 weeks (median viral load drop 2.6 logs). All three patients in this series improved after the reintroduction of steroids and a change of anti-PCP therapy. Alternative management strategies may include delaying the introduction of HAART in the early stages of PCP or prolonging steroid use if HAART is commenced. Given that we observed this phenomenon in approximately one-fifth (18.8%) of PCP patients presenting to our unit, the possibility of immune restoration inflammatory syndrome, particularly in patients with severe PCP and advanced HIV disease in whom HAART is started early, should be considered.
Royal Sussex County Hospital Brighton, United Kingdom REFERENCES
From the Authors Dean and colleagues are confirming our previous observation on the risk of paradoxical worsening after introduction of HAART in patients with Pneumocystis carinii pneumonia (PCP) (1). Since the publication of our paper, we observed three new cases. The 18% prevalence of paradoxical worsening of PCP reported by Dean and colleagues is higher than that we have previously shown. In our experience, paradoxical worsening of PCP represents 4.6% of the patients referred for PCP to our instititution, and 7% of those receiving steroids because of acute respiratory failure. This discrepancy probably reflects variation of the incidence of severe PCP between institutions, and the diversity of schedules of adjunctive steroid therapy and of HAART introduction used in severe PCP (2, 3). All the patients reported with paradoxical worsening of PCP had a very similar presentation. All had severe PCP (PaO2 < 70 mm Hg) requiring adjunctive steroids. Moreover, HAART was introduced early after PCP diagnosis (1 to 16 days) and steroid therapy was stopped too early (< 15 days). Lastly, this phenomenon occurs in severely immunocompromised patients in whom a dramatic decrease of plasma viral load was observed after HAART introduction. The peripheral blood CD4 cell counts did not increase in parallel, suggesting CD4 cell pulmonary sequestration as shown in lung tissue specimen (1). However, it is also important to emphasize that the diagnosis of paradoxical PCP worsening implies that cotrimoxazole-resistant PCP, pulmonary superinfection, and drug-induced pulmonary toxicity have been previously ruled out. Finally, the fact that patients with paradoxical PCP worsening improved after HAART discontinuation or steroid introduction suggests either the need for an overlap period between HAART introduction and steroid cessation in the case of early HAART introduction, or to delay HAART introduction until after the end of PCP steroid adjunctive therapy. Whatever the measure adopted to prevent paradoxical PCP worsening after HAART introduction, steroid adjunctive therapy might probably not be shorter than 3 weeks, as recommended by consensus statement (4).
Hôpital Tenon and Université Paris VI, UFR Saint-Antoine Paris, France REFERENCES
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