Does cyclosporin A affect CCR5 and CXCR4 expression in primary HIV-1-infected patients?

Priscilla Biswas, Andrea Galli, Laura Galli, Chiara Tassan Din, Andrea Vecchi, Mauro Malnati, Adriano Lazzarin, Giuseppe Tambussi

Research output: Contribution to journalArticle

Abstract

Background: CCR5 and CXCR4 are the major coreceptors of HIV required for successful viral entry. No information exists on the effect of cyclosporin A (CsA) on expression of CCR5 and CXCR4. A longitudinal study of the coreceptors' expression in freshly isolated peripheral blood mononuclear cells (PBMC) of patients with primary HIV infection (PHI) was performed. Methods: Patients received highly active antiretroviral therapy (HAART) alone (n = 7) or with CsA (HAART + CsA) (n = 8). Flow cytometric data were analyzed at TO (baseline), two (T2), six (T6), and twelve (T12) months after therapy initiation. Results: At TO PHI subjects presented a statistically significant higher count and percentage of CD8+CCR5+ lymphocytes compared to healthy donors (HD) (mean ± SD, 2,240 ± 1,998 vs 181 ± 89 cells/μl). Conversely, CD4+CXCR4+ lymphocytes were less abundant in PHI than in HD (443 ± 337 vs 673 ± 339 cells/μl), whereas CD4+CCR5+ lymphocytes were substantially comparable (169 ± 167 vs 126 ± 60 cells/μl). In the follow up no differences between HAART and HAART + CsA groups reached statistical significance in CD4 lymphocytes. CD4+CCR5- lymphocytes displayed a rapid recovery after therapy initiation, similarly to the CD4+CXCR4+ subset. In CD8 lymphocytes a statistically significant difference between HAART and HAART + CsA patients occurred at T2 when HAART + CsA patients presented a lower absolute count of the CD8+CXCR4+ subset compared to the HAART group. The major change after therapy initiation in all PHI patients was a striking drop of CD8+CCR5+ lymphocytes; moreover, the CD8+CXCR4- subset behaved similarly. The decrement of CD8+CCR5+ lymphocytes paralleled the decline of viremia and CD8+CD38+ lymphocytes, with the sharpest slope at T2. Conversely, RANTES levels increased at T2 and remained elevated during the follow up. Conclusions: CsA cotreatment in PHI patients appears not to substantially modify HIV coreceptors' expression in PBMC. However, this novel piece of information should be used with caution, since this was not a randomized study between the HAART and the HAART + CsA groups.

Original languageEnglish
Pages (from-to)433-441
Number of pages9
JournalCytometry Part B - Clinical Cytometry
Volume72
Issue number6
DOIs
Publication statusPublished - Nov 2007

Keywords

  • CCR5
  • CXCR4
  • Cyclosporin A (CsA)
  • HIV coreceptors
  • Primary HIV infection (PHI)
  • RANTES
  • Viremia

ASJC Scopus subject areas

  • Hematology
  • Cell Biology
  • Pathology and Forensic Medicine
  • Biophysics
  • Endocrinology

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