Karpas A; International Conference on AIDS.
Int Conf AIDS. 1994 Aug 7-12; 10: 114 (abstract no. PA0338).
University of Cambridge Dept Haematology, UK.
OBJECTIVE: To determine whether FK 506 is likely to benefit patients with HIV disease. METHODS: We have compared the effects of FK 506 with its structural analogue, Rapamycin, on the replication of HIV-1 infected and non-infected T-cells. RESULTS: FK 506 was found to selectively inhibit the growth of HIV infected cells at concentrations which did not inhibit the growth of uninfected cells. In contrast, Rapamycin inhibited the growth of HIV infected and uninfected T-cells to the same degree. FK 506 was also found to reduce cell-to-cell transmission of HIV and reduce viral production by infected cells. DISCUSSION AND CONCLUSION: Unlike Rapamycin, FK 506 was shown to be a selective inhibitor of HIV infected T-cells as well as reduce viral production and cell to cell transmission. It is, therefore, likely to suppress HIV induce immune activation in vivo. FK 506 also blocks TNF production (Goldfeld et al, PNAS 89: 12198, 1992) which is highly elevated in patients with HIV disease. Since TNF amplifies the viral cytopathic effect and induces cachexia which leads to emaciation, FK 506 is likely to delay the progression to AIDS through these two independent pathways. Since FK 506, but not Rapamycin, modulates Calcineurin activity and prevents formation of NF-AT (nuclear factor of activated T-cells), which are cellular rather than viral targets, HIV is less likely to develop resistant mutants.
Publication Types:
Keywords:
- Acquired Immunodeficiency Syndrome
- Anti-HIV Agents
- Calcineurin
- HIV
- HIV Core Protein p24
- HIV Infections
- HIV Seropositivity
- HIV-1
- Humans
- Sirolimus
- T-Lymphocytes
- Tacrolimus
- immunology
- therapy
Other ID:
UI: 102209891
From Meeting Abstracts