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Background:  Immune activation is a chief mechanism of HIV-1 infection-associated disease. Decreasing immune activation coupling cyclosporin A (CsA) with HAART during primary HIV-1 infection (PHI) may be beneficial for both virologic and immunologic measures.

Methods:  In an open-label, prospective, controlled trial, 77 adults with PHI have been treated with PI-containing HAART, either alone (n = 43, control group) or coupled with an 8-week course of CsA (n = 34, CsA group) at a dose achieving CsA blood levels stably > 100 ng/mL. In an intent-to-treat analysis, immunologic and virologic measures were compared over 120 weeks in the 2 groups, both with a median follow-up of 28 months (range 3 to 36). Plasma viral load was measured with Amplicor assay (LOD 50 copies/mL).

Results:  Mean baseline values, including time of exposure to HIV-1, interval between onset of PHI symptoms and initiation of HAART, viral load (5.86 vs 5.64 log₁₀ copies/mL, p = 0.33), and CD4⁺ T-cell counts (480 vs 461 cells/μL, p = 0.73), were comparable in the 2 groups. Viral load suppression over time was similar in both groups. However, the proportion of patients achieving viral load < 50 copies/mL was significantly higher in CsA than in the control group at weeks 18, 24, and 36 (p = 0.011). In CsA and the control group, respectively, the mean increase in CD4⁺ T-cell counts over baseline was 428 vs 109 cells/μL at week 1 (p < 0.001), 379 vs 217 cells/μL at week 2 (p = 0.013), and 373 vs 201 cells/μL at week 4 (p = 0.003). In the CsA group only, viral load extent predicted the increase over baseline in CD4⁺ T cells at week 2 (β 0.45, 95% CI 28 to 328, p = 0.022, regression analysis), suggesting that CsA prevents sequestration of CD4⁺ T cells from lymph nodes reducing the heightened state of cellular activation. Moreover, CD4/CD8 ratio (CsA group 0.4; control group 0.48, at baseline) normalized significantly more rapidly in CsA vs control group: 1.09 vs 0.78 (p = 0.02) at week 2, 1.14 vs 0.79 (p = 0.005) at week 4, and 1.25 vs 0.69 (p = 0.001) at week 8. Importantly, the rapid CsA-induced beneficial effect on CD4⁺ T-cell changes was maintained over time, the mean CD4⁺ T cell-counts in CsA vs control group being: 928 vs 697 cells/μL (p = 0.006) at week 24, 1114 vs 790 (p = 0.015) at week 60, and 1115 vs 888 (p = 0.07) at week 120. Finally, CsA was safe in all patients, and adherence to HAART was good in both groups.

Conclusions:  The rapid shutdown of immune activation in PHI can have long-term beneficial effects and establish a more favorable immunologic set-point.

Keywords: primary HIV-1 infection; cyclosporin A; immune-based therapies