Chloroquine exerts an additive in vitro anti-HIV type 1 effect when associated with didanosine and hydroxyurea

Several groups, including ours, have reported that chloroquine (CQ) or its analog hydroxychloroquine has anti-HIV-1 activity both in vitro and in vivo . We studied in vitro whether the addition of CQ to the combination of hydr oxyurea (HU) plus didanosine (ddI) had an additive effect in inhibiting the replication of HIV-1. Therefore both the H-9 T lymphocytic cell line and t he U-937 promonocytic cell line as well as primary T cells and monocytes we re infected with HIV-1 and then treated with HU at 0.2 mM and ddI at 1 mu M and varying concentrations of CQ, Addition of CQ resulted in an additional inhibition of HIV-1 replication, as assessed by reverse transcriptase (RT) activity, with a CQ EC50 Of 0.4-0.9 mu M for the cell lines and of 0.2-0.9 mu M for the primary cells, Similarly, addition of CQ further inhibited HI V-1 replication in U-1 cells stimulated either with LPS or H2O2 and in ACH- 2 cells stimulated either with PMA or H2O2, with CQ EC50 values of 0.1 and 1 mu M, respectively. Under the experimental conditions used, CQ induced ne ither toxicity nor apoptosis in the H-9 and U-937 cells, This in vitro addi tive anti-HIV-1 activity of CQ, in combination with HU + ddI, supports the idea that this triple regimen should be studied in clinical trials, It may become of particular interest to HIV-1-infected individuals from the develo ping world, in view of the low cost of both CQ and HU.