The enigma of the clandestine association between chloroquine and HIV-1 infection

Abstract

Objectives: The antimalarial drug chloroquine (CQ) dampens the immune system and is used in the treatment of autoimmune disorders. CQ also shows antiviral activity against nonenveloped and enveloped viruses, including HIV-1. Persistent immune activation in chronic HIV-1infection leads to CD4 T-cell depletion. CQ is envisioned to attenuate immune activation and virus activity in HIV-1-infected patients. The role of CQ in immune activation and virus activity is discussed here.

Methods: To elucidate the effect of CQ on immune activation, a retrospective review of published clinical trials, in vivo experimental studies in animals, and the most relevant in vitro observations in HIV-1-infected cells, together with observations from our own laboratory studies, was carried out and the findings discussed.

Results: In a few clinical studies and animal experiments, CQ was ineffective in decreasing immune activation and HIV-1 infection. In vitro, CQ markedly increased HIV-1 infection in astrocytes and other non-CD4 cells.

Conclusions: The use of CQ in HIV-1-infected patients is questionable. The evidence for a dampening of immune activation by CQ is inconclusive.

Keywords: HIV-1; chloroquine; endocytosis; immune activation; non-CD4 cells.