Does cyclosporin A affect CCR5 and CXCR4 expression in primary HIV-1-infected patients?
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 T0 (baseline), two (T2), six (T6), and twelve (T12) months after therapy initiation.


RESULTS
At T0 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/microl). Conversely, CD4+CXCR4+ lymphocytes were less abundant in PHI than in HD (443 +/- 337 vs 673 +/- 339 cells/microl), whereas CD4+CCR5+ lymphocytes were substantially comparable (169 +/- 167 vs 126 +/- 60 cells/microl). 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.
Biswas
Priscilla
P
Laboratory of Clinical Immunology, San Raffaele Scientific Institute, Milan, Italy. Pricilla.Biswas@hsr.it
Galli
Andrea
A
Galli
Laura
L
Tassan Din
Chiara
C
Vecchi
Andrea
A
Malnati
Mauro
M
Lazzarin
Adriano
A
Tambussi
Giuseppe
G
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D018946:Chemokine CCL5 / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D015497:HIV-1; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D019713:Receptors, CCR5 / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism*
D018946:Chemokine CCL5; D007166:Immunosuppressive Agents; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D016572:Cyclosporine