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Immune reconstitution CMV pneumonitis
  1. R F Miller,
  2. P J Shaw,
  3. I G Williams
  1. Department of Sexually Transmitted Diseases, Royal Free and University College Medical School, Mortimer Market Centre, Mortimer Market, off Capper Street, London WC1E 6AU

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    Editor,—A 41 year old white homosexual man presented in late July 1999 with a 5 day history of exertional dyspnoea, non-productive cough, fever with sweats, and anorexia. An empirical course of broad spectrum antibiotics did not improve his symptoms and Sao2 remained ⩽95% on air at rest. The chest radiograph showed non-specific abnormalities. He had been found to be HIV-1 antibody positive in August 1991; cutaneous Kaposi's sarcoma defined AIDS in June 1992. In May 1995 biopsy confirmed cytomegalovirus (CMV) oesophagitis and colitis were treated with intravenous ganciclovir for 2 weeks; no maintenance therapy was given. At this time the CD4 count was 130 cells ×106/l. In October 1996 the patient had Pseudomonas aeruginosa pneumonia. He had a complex antiretroviral history, having taken combinations of reverse transcriptase inhibitors and protease inhibitors. He had discontinued all antiretroviral therapy in January 1999 as therapy had failed to maintain CD4 counts and HIV viral load had risen: co-trimoxazole primary Pneumocystis carinii pneumonia prophylaxis had been continued. In early June 1999 HIV viral load had risen to 223 000 copies/ml and CD4 count had fallen to 70 cells ×106/l. Two weeks before the onset of respiratory symptoms the patient had recommenced antiretroviral therapy with d4T, 3TC, and amprenivir/saquinavir. Four weeks after starting antiretroviral therapy viral load had fallen to 1500 copies/ml and CD4 had risen to 170 cells ×106/μl. A computed tomography (CT) scan of the thorax 4 weeks after the onset of respiratory symptoms and 6 weeks after starting antiretroviral therapy showed focal areas of ground glass shadowing, largely in the left upper lobe but also involving other lobes; in addition, chronic changes resulting from the previous episode of pneumonia were noted, including multifocal fibrotic change with thickened interlobular septae, cystic air spaces, and minor bronchiectasis involving all lobes. Repeat viral load at this time = 200 copies/ml and CD4 = 160 cells ×106/l. At bronchoscopy, performed after 8 weeks of antiretroviral therapy, the endobronchial appearances were normal. Bronchoalveolar lavage (BAL) was performed from the left upper lobe. Analysis of BAL fluid revealed a lymphocytic reaction; many cells had intranuclear/cytoplasmic inclusions typical of CMV infection. In situ hybridisation for CMV was positive. Staining and culture for bacteria, mycobacteria, P carinii and other fungi were negative. Intravenous ganciclovir 10 mg/kg per day was given for 21 days, in addition, antiretroviral therapy and co-trimoxazole were continued. With this there was a rapid defervescence of fever, a reduction in exertional dyspnoea and improvement in Sao2 to ⩾98% on air. Repeat CT of the thorax after 3 weeks of intravenous ganciclovir showed an improvement in ground glass shadowing and persistence of the chronic changes. The patient was subsequently maintained on oral ganciclovir.

    The diagnosis of CMV pneumonitis was made by identifying CMV as the sole pathogen in BAL fluid and the improvement in symptoms, Sao2, and CT appearances with ganciclovir as monotherapy. This diagnosis was made in the context of a rapidly falling viral load and an increase in CD4 count indicating partial immune reconstitution.

    Partial restoration of cell mediated immunity induced by antiretroviral therapy, as shown by recovery of part of CD4 T cell reactivity to memory antigens,1, 2 may cause development of sufficient inflammatory responses to produce symptoms and signs in patients latently infected with opportunistic infections. Reactivation mycobacterial lymphadenitis,3 cryptococcal meningitis,4 and CMV retinitis5, 6 have been described. The case described here suggests CMV pneumonitis should be added to the list of immune reconstitution phenomena.


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