Extraordinary results with cyclosporin A plus HAART for primary HIV infection

Treatment of Primary HIV-1 Infection with Cyclosporin A Coupled with Highly Active Antiretroviral Therapy [Rizzardi GP et al. J Clin Invest 2002;109:681]: This is a report from Giuseppe Pantaleo et al. from Milan, Italy and colleagues from Lausanne, Switzerland addressing the issue of treatment of primary HIV infection by combining HAART with cyclosporin A to rapidly shut down immune activation. The authors studied nine consecutive adult patients treated with cyclosporin A (0.3-0.6 mg/kg po q12h) combined with d4T, 3TC, nelfinavir (1,250 mg bid) and saquinavir (Fortovase 1200 mg bid). Cyclosporin was continued through week eight and then discontinued, and the patients were followed for 64 weeks. Controls were 29 patients given HAART regimens with two PIs at the time of diagnosis of primary HIV infection using the same criteria for primary HIV: the presence of clinical symptoms of acute HIV infection with positive plasma HIV RNA and negative HIV serology. Viral suppression was comparable in the two groups, but cyclosporine treatment was associated with an extraordinary early CD4 cell response that was sustained over the 64 weeks of study. These results are summarized in the following table:

* Estimates from figures (absolute numbers were not provided)

The authors also demonstrated that HIV-1-specific CD8 and CD4 cell responses were comparable in the two groups. The substantial increase in CD4 cells included both naive and memory CD4 cells at week one as well as later. They also showed retention of CMV- and EBV-specific CD8 cell responses. They conclude that "rapid shut down of T cell activation in the early phases of primary HIV-1 infection can establish a more favorable immunologic set-point."

Comment: The mechanism of action of cyclosporin A is presumably a decrease in the magnified cell activation that results in activated CD4 cells that support massive HIV replication in early stage HIV infection. The results at seven days were extraordinary in terms of CD4 cell rebound. Both groups had normal mean CD4 cell counts at 64 weeks, although those receiving cyclosporin A plus HAART had mean levels that were 500/mm3 higher.

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