Tryptophan depletion and HIV infection: a metabolic link to pathogenesis

HIV-1-infected patients have low circulating tryptophan concentrations despite evidence of adequate dietary intake of this essential amino acid. A chronic increase in inducible tryptophan oxidation is the basis of HIV-1-associated tryptophan depletion. This metabolic process results in the irretrievable loss of tryptophan molecules from the available pool. Such sustained disruption of normal tryptophan metabolism over time disturbs the many metabolic processes involving this amino acid, and has been implicated in some features of AIDS pathogenesis. Normal T-cell function is adversely affected by tryptophan depletion, but the extent of the effect in HIV-1-infected patients is still unclear. Attempting to directly supplement tryptophan is not advised given the potential increase in circulating concentrations of neurotoxic intermediates. Although only preliminary data are available, evidence suggests that antiretroviral and nicotinamide treatments can boost plasma tryptophan concentrations in HIV-1-infected patients and impact the secondary effects of tryptophan depletion. Additional study of this metabolism could lead to improved treatment strategies for patients with HIV infection. In this review I focus on the potential links between disturbed tryptophan metabolism and pathogenesis.