Ciclosporin (Neoral / Sandimmun)

Ciclosporin (Neoral / Sandimmun) is a powerful immunosuppressive drug. It acts by inhibiting T-helper cell functions and blocking production of the cytokine interleukin-2. Ciclosporin is used to prevent rejection after a transplant.

Possible side-effects of ciclosporin include liver and kidney impairment, stomach upsets, increased hair growth, receding gums and high blood levels of calcium.

With liver and kidney transplants now being performed among HIV-infected people, drug interactions between ciclosporin and antiretroviral agents are being investigated. A dose reduction in ciclosporin may be required in patients taking protease inhibitors.1 2 In contrast, non-nucleoside reverse transcriptase inhibitors (NNRTIs) seem to reduce ciclosporin levels.3

Ciclosporin has also been investigated as an anti-HIV drug. The use of ciclosporin for HIV is unlicensed and experimental, but may be an attractive drug because HIV cannot develop resistance to it.

Immunosuppressive drugs can prevent the decline in CD4 cell counts by inhibiting the over-activation of CD4 T-cells that is responsible for their death in patients with HIV. In test tube studies, ciclosporin prevents apoptosis and the development of syncytia, useless clumps of uninfected CD4 T-cells that form around a single infected CD4 T-cell.4 5 It can also prevent HIV from infecting blood cells, particularly when combined with AZT (zidovudine, Retrovir).6 Ciclosporin can also inhibit the activity of a cellular protein called cyclophilin A, which is thought to trigger the destabilisation of a virus particle after it infects a new cell.

A review of the medical literature on people who were infected with HIV through transplants found that people who received ciclosporin were less likely to develop AIDS over five years than people who did not receive it.7

Ciclosporin has also been used in primary HIV infection alongside antiretroviral therapy in order to restrict immune activation. A study in nine patients with primary HIV infection found that ciclosporin led to greater gains in CD4 cell counts.8

References

  1. Frassetto LA et al. Cyclosporine pharmacokinetics and dosing modifications in human immunodeficiency virus-infected liver and kidney transplant recipients. Transplantation 80: 13-17, 2005
  2. Guaraldi G et al. Pharmacokinetic interaction between amprenavir / ritonavir and fosamprenavir on cyclosporine in two patients with human immunodeficiency virus infection undergoing orthotopic liver transplantation. Transplant Proc 38: 1138-1140, 2006
  3. Tseng A et al. Probable interaction between efavirenz and cyclosporin. AIDS 16: 505-506, 2002
  4. Groux H et al. Activation-induced death by apoptosis in CD4+ T cells from human immunodeficiency virus-infected asymptomatic individuals. J Exp Med 175: 331-340, 1992
  5. Karpas A et al. Inhibition of human immunodeficiency virus and growth of infected T cells by the immunosuppressive drugs cyclosporin A and FK 506. Proc Natl Acad Sci U S A 89: 8351-8355, 1992
  6. Vaccarezza M et al. Cyclosporin A cooperates with AZT in suppressing HIV-1 infection in primary T-lymphocytes acutely infected in vitro. First National Conference on Human Retroviruses, Washington, abstract 583, 1993
  7. Schwartz A et al. The effect of cyclosporine on the progression of human immunodeficiency virus type 1 infection transmitted by transplantation - data on four cases and review of the literature. Transplantation 55: 95-103, 1993
  8. Rizzardi GP et al. Treatment of primary HIV-1 infection with cyclosporin A coupled with highly active antiretroviral therapy. J Clin Invest 109: 681-688, 2002