Anti-HIV effects of the malarial drug chloroquine
Paul Blanchard, HIV i-Base
Chloroquine is a cheap and widely available drug, which has been used extensively and for many years in the treatment and prophylaxis of malaria.
Now, new data from in-vitro studies confirms a wide spectrum of activity against HIV-1 replication. A related compound, hydroxychloroquine also has evidence supporting an anti-HIV effect in HIV-infected patients.
A team of researchers led by Savarino and colleagues from the University of Turin, Italy, chose to study chloroquine instead of hydroxychloroquine because of its greater availability in resource poor countries.
The current research performed a number of screens and assays of the activity of chloroquine against both a range of HIV viral targets and different strains of the virus itself. In addition, activity in different cell types and cell lines was assessed.
The results clearly indicated that chloroquine at clinically achievable concentrations inhibits HIV-1 replication mainly by affecting the production of the viral envelope glycoproteins, and that the drug has broad spectrum activity against X4 and R5/X4 isolates from subtypes A-E and against HIV-2. The study also showed that chloroquine exerts these antiviral effects in peripheral blood mononuclear cells (PBMC) and that these effects are not confined to laboratory strains.
In considering further studies and clinical trials of chloroquine for HIV-infection the researchers note that the toxicity of chloroquine has been studied for much longer than any of the currently available antiretroviral drugs. It is also widely available and one of the cheapest drugs so far shown to have anti-HIV activity in addition to having some activity towards some AIDS-related opportunistic infections. A further attractive property of this compound is its inhibitory effect on the synthesis of the pro-inflammatory cytokines TNF-alpha, IL-1 and IL-6, which may also, in turn, have favourable effects on the milieu of HIV-disease.
It should also be noted that for a number of reasons chloroquine may be attractive as an anti-HIV drug in developed world settings. The effects of chloroquine on the maturation of the viral envelope glycoproteins inhibit viral replication at another step of the HIV-replication cycle. Additive in-vitro activity has also been demonstrated in combination with zidovudine and the combinations of didanosine and hydroxyurea or zidovudine and hydroxyurea. With inhibition of gp120 being the likely primary mechanism of action of chloroquine it appears that the drug affects cellular enzymes so that the likelihood of the emergence of resistance during chloroquine therapy would be low.
The team conclude their work by calling for further studies of this promising drug including clinical trials.
Savarino A, Gennero L, Chen HC et al. Anti-HIV effects of chloroquine: mechanisms of inhibition and spectrum of activity. AIDS 2001 Nov 23;15(17):2221-9.