title: Chloroquine exerts an additive in vitro anti-HIV type 1 effect when associated with didanosine and hydroxyurea.
abstract: 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 hydroxyurea (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 the U-937 promonocytic cell line as well as primary T cells and monocytes were infected with HIV-1 and then treated with HU at 0.2 mM and ddI at 1 microM 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 microM for the cell lines and of 0.2-0.9 microM for the primary cells. Similarly, addition of CQ further inhibited HIV-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 microM, respectively. Under the experimental conditions used, CQ induced neither toxicity nor apoptosis in the H-9 and U-937 cells. This in vitro additive 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 developing world, in view of the low cost of both CQ and HU.
authors.affiliation: Unit for Renal and Infectious Diseases, Algemeen Ziekenhuis St-Jan, Brugge, Belgium. j.r.boelaert.brugge@unicall.be
authors.forename: J R
authors.initials: JR
authors.lastname: Boelaert
authors.forename: K
authors.initials: K
authors.lastname: Sperber
authors.forename: J
authors.initials: J
authors.lastname: Piette
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000633:toxicity; D017209:Apoptosis; D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology* / Q000633:toxicity; D016049:Didanosine / Q000494:pharmacology* / Q000633:toxicity; D004357:Drug Synergism; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology* / Q000633:toxicity; D009000:Monocytes / Q000187:drug effects / Q000821:virology; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology* / Q000633:toxicity; D013601:T-Lymphocytes / Q000187:drug effects / Q000821:virology; D020298:U937 Cells; D014779:Virus Replication / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D002738:Chloroquine; D016049:Didanosine; D006918:Hydroxyurea