759   Effect of Cyclosporin A in Combination with Highly Active Antiretroviral Therapy in Primary HIV-1 Infection.

G. P. Rizzardi*¹, B. Capiluppi², G. Tambussi², J. P. Chave³, P. Champagne¹, A. Harari¹, A. Lazzarin², and G. Pantaleo¹.
¹CHUV, Lausanne, Switzerland;²HSR, Milan, Italy; and³Clin. de La Source, Lausanne, Switzerland.

Background:The objective of this study was to test safety and activity of cyclosporin A (CsA) in combination with highly active antiretroviral therapy (HAART) during primary HIV-1 infection (PHI) on virologic and immunologic measures.

Methods:Nine adults (CsA group) with PHI have been prospectively treated with CsA (0.6—1.2 mg/kg) along with HAART. All patients discontinued CsA at week 8 and maintained HAART. Plasma viral load (VL) was measured with Amplicor assay (LOD: 50 copies/ml). Tetramer analysis and ki67 expression were used to test HIV-1-specific CD8 T cell responses and the proportion of cycling cells, respectively. Immunologic and virologic measures in CsA group were compared with those of 29 consecutive PHI patients treated with HAART only (control group) over 64 weeks.

Results:Baseline values, including time of exposure to HIV-1, duration of PHI symptoms, VL (5.82 vs. 5.76 log₁₀copies/ml, P = 0.87), and CD4 count (527 vs. 441 cells/ml, P = 0.35) were comparable in the 2 groups. VL suppression over time was similar in both groups. In the CsA and in the control group, respectively, the mean increase in CD4⁺T cell counts over baseline was 615 vs. 123 cells/ml at week 1 (P = 0.027), 491 vs. 188 cells/ml at week 2 (P = 0.045), and 568 vs. 198 cells/ml at week 4 (P = 0.017). In the CsA group, the increase over baseline in CD4⁺T cells at week 2 was positively correlated with VL (r = 0.85, P = 0.004, N = 9), whereas it was not correlated with the number of proliferating CD4⁺T cells (r = 0.14, P = 0.9, N = 9), suggesting that this increase did not result from new cell production. Interestingly, CD4⁺T cell counts were constantly higher in the CsA vs. the control group over time (1443 vs. 712 cells/ml at week 64, P = 0.008). Similar changes occurred in percent values of CD4⁺T cells. CD4/CD8 ratio (0.46 vs. 0.41 at baseline) normalized significantly more rapidly in the CsA vs. control group (1.26 vs. 0.78, P = 0.046, at week 4). HIV-1-specific CD8 responses are maintained during CsA treatment. CsA was safe in all patients.

Conclusions:Addition of CsA very rapidly restores both percent and absolute numbers of CD4⁺T cells, preventing activation and sequestration of CD4⁺T cells into lymphoid tissue.