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JAC Advance Access published online on July 1, 2003
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkg314
© 2003 by The British Society for Antimicrobial Chemotherapy
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© 2003 The British Society for Antimicrobial Chemotherapy

Original article

Assessment of immune reconstitution to Pneumocystis carinii in HIV-1 patients under different highly active antiretroviral therapy regimens

Chiara Atzori 1 *, Mario Clerici 2 , Daria Trabattoni 2 , Giovanna Fantoni 1 , Antonella Valerio 1 , Elisa Tronconi 1 , and Antonietta Cargnel 1

1 II Department of Infectious Diseases, L. Sacco Hospital, Via G.B. Grassi 74, 20157, Milan
2 Preclinic Department of Immunology, L. Sacco Hospital, Milan University, Milan, Italy

* Corresponding author. E-mail: c.atzori{at}hsacco.it.

Received 11 February 2003 ; revised 29 April 2003 ; accepted 29 April 2003

Abstract

The introduction of protease inhibitors (PIs) gave a dramatic drop in AIDS-related opportunistic events, mainly due to induced immune reconstitution. Discontinuation of prophylaxis against Pneumocystis carinii is considered safe when CD4 > 200 cells/mm3. Ideally, we should have specific functional tests for HIV-1-related decisions. We examined viro-immunological profiles, clinical outcome and lymphocyte proliferation (LP) to P. carinii and other antigens in 108 subjects: 28 AIDS presenters with P. carinii pneumonia (PCP) (CD4 < 200 cells/mm3), 22 untreated asymptomatic HIV-1-infected patients (CD4 > 200 cells/mm3), 44 HIV-1-infected patients immune-reconstituted on antiretroviral regimens and 14 HIV-1-uninfected healthy controls. As regards viral load, there was no significant difference in therapy duration, nadir, or actual CD4, CD8, natural killer or B cell counts in immune-reconstituted patients receiving protease inhibitor (PI)-based versus those receiving PI-sparing antiretroviral regimens. Among subjects showing abnormally low P. carinii-specific LP, three patients receiving a non-nucleoside reverse transcriptase inhibitor (nNRTI) developed PCP despite having CD4 > 250 cells/mm3. P. carinii-specific LP could be considered for doubtful situations, i.e. for a safer clinical decision of discontinuing or restarting prophylaxis in patients with a low CD4 nadir or experiencing a sudden CD4 decrease under highly active antiretroviral therapy (HAART). HIV-1 PIs, having in vitro aspecific effects against Pneumocystis, could play a clinically significant anti-opportunistic role, thus offering a further benefit in heavily immunosuppressed patients during early stages of antiretroviral therapy.

Keywords: immune reconstitution, lymphocyte proliferation, Pneumocystis carinii, highly active antiretroviral therapy, protease inhibitors
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