JAC Advance Access originally published online on February 12, 2004
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Journal of Antimicrobial Chemotherapy (2004) 53, 494-500
© 2004 The British Society for Antimicrobial Chemotherapy
Inverse correlation between CD8+ lymphocyte apoptosis and CD4+ cell counts during potent antiretroviral therapy in HIV patients
1 Department of Experimental Medicine and Biochemical Science, ‘Tor Vergata’ University Hospital, and 5 Department of Neuroscience, University of Rome ‘Tor Vergata’, Via Montpellier 1, 00133 Rome; 2 Department of Infectious and Tropical Diseases, University of Rome ‘La Sapienza’, Viale del Policlinico 155, 00161 Rome; 3 Clinical Immunology Unit, S. Giovanni Hospital, Via Codirossoni, 00169 Rome; 4 Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome; 6 IRCCS, S. Lucia, Via Ardeatina 306, 00179 Rome; 7 Department of Microbiological, Genetic and Molecular Sciences, University of Messina, Salita Sperone 31, 96168 Messina, Italy
Received 3 September 2003; returned 22 October 2003; revised 24 November 2003; accepted 8 December 2003
Objectives: We have addressed the relationships between inhibition of CD4+ and CD8+ cell apoptosis and CD4+ cell recovery in HIV patients undergoing potent antiretroviral therapy (PART) by correlating apoptosis levels with virological and immunological parameters detected over a long-term period in HIV patients undergoing therapy.
Patients and methods: Twenty-two HIV-1-infected patients undergoing PART were enrolled in a long-term, open longitudinal study. Data derived from 17 patients with successful response to therapy (TS; median time of follow-up 36 months, range 24–36 months) were used for correlation studies. Apoptosis was evaluated after short-term culture of peripheral blood lymphocytes by flow cytometry analysis of isolated nuclei or of annexin V/CD4, annexin V/CD8 double-stained cells.
Results: Sustained, noticeable levels of apoptosis inhibition in peripheral blood mononuclear cells were measured, in the long-term, in 16 of the 17 TS patients. Levels of total cell apoptosis correlated with levels of CD8+ apoptotic cells more significantly than with levels of CD4+ apoptotic cells. In addition, CD4+ cell counts were correlated inversely with levels of CD8+ apoptotic cells in a highly significant fashion, but not with levels of CD4+ apoptotic cells.
Conclusions: Our data indicate that the increase of CD4+ lymphocytes in HIV patients, as a consequence of successful response to PART, may be related to changes in apoptosis level occurring in the CD8+, and not in the CD4+, cell compartment.
Keywords: HIV, antiviral, CD8+ cells
* Correspondence address. Department of Neuroscience, University of Rome ‘Tor Vergata’, Via Montpellier 1, 00133 Rome, Italy. Tel: +39-06-72596392; Fax: +39-06-20427282; E-mail: macchi{at}med.uniroma2.it
B. Macchi and A. Mastino contributed equally to this work.
¶ B. Macchi and A. Mastino contributed equally to this work.