Behandeling van HIV-infecties. De schuilplaatsen van het virus

The introduction of Highly Active Anti-Retroviral Therapy (HAART) for the treatment of an HIV infection in 1996 has resulted in an enormous reduction of morbidity and mortality. Complete eradication of virus is, however, not yet possible. Sanctuary sites appear to be of paramount importance in the failure of eradication of HIV. A sanctuary site is a cell or an organ with reduced susceptibility of HIV to antiretroviral therapy. Inadequate availability of (the active form of) drugs at the site of action due to efflux pumps such as P-glycoprotein (Pgp) or inadequate bioactivation and the presence of latent virus (with reduced susceptibility to therapy) may be mechanisms that result in sanctuary sites. CD₄+ memory cells, macrophages, follicular dendritic cells, the central nervous system and testes are examples of these sanctuary sites. Use of Pgp inhibitors and CD₄+ activators may contribute to circumvent these sites and may aid to eradicate the last virus particles. The existence of sanctuary sites may also enhance the development of resistant virus. Therapy directed at eradication of virus in these sanctuary sites may thus form an important improvement in the treatment of HIV-infected patients.