New drug combinations for the treatment of murine AIDS and macrophage protection

Background The failure of highly active antiretroviral therapies (HAART) is mainly due to the existence of latent infected reservoirs, such as macroph ages and resting CD4+ T cells. In this paper, we report the results that we obtained in a murine model of AIDS by alternating the administration of th e lympholitic drug 2-Fluoro-ara-AMP (Fludarabine) to eliminate the infected cells, with that of Azidothymidine (AZT) plus reduced glutathione (GSH) en capsulated in erythrocytes, to protect lymphocytes and macrophages not yet infected, respectively. Materials and methods Two groups of infected mice were treated as follows: one group was treated by alternating the administration of Fludarabine and AZT (treatment A), while the other group received the same treatment plus G SH-loaded erythrocytes given with AZT (treatment A + L-RBC). Fludarabine wa s administered intraperitoneally, AZT in the drinking water and GSH was enc apsulated in erythrocytes by a procedure of hypotonic dialysis and isotonic resealing. Results The results obtained show that GSH-loaded erythrocytes provide addi tive effects in all the parameters examined. Conclusions Alternation of a lympholitic drug and antiretroviral drug is ef fective in reducing the progression of murine AIDS. Addition of a system to protect macrophages provides additive effects in almost all the parameters considered, confirming that combination therapies aimed at protecting diff erent infectable cell compartments are better than treatments protecting ma inly lymphocytes.