Increased blood phenylalanine to tyrosine ratio in HIV-1 infection and correction following effective antiretroviral therapy

Objective: Higher blood levels of the essential amino acid phenylalanine (phe) have been documented in patients with HIV-1 infection. They may relate to a diminished conversion of phe to tyrosine (tyr) by the enzyme phenylalanine-hydroxylase (PAH). PAH is rate-limiting in the biosynthesis of dopamine, and impaired PAH activity is reflected by an increased phe to tyr ratio (phe/tyr). Methods: Plasma phe/tyr was measured in 107 patients with HIV-1 infection before and after 12 months of effective antiretroviral therapy (ART). Results were compared with CD4(+) cell counts, HIV-1 RNA levels and concentrations of immune activation marker neopterin. Results: Before ART, phe/tyr was mean S.D.: 0.99 +/- 0.57 mu mol/mu mol. Phe/tyr correlated significantly with plasma and urine neopterin concentrations (rs = 0.434, and rs = 0.392; both p < 0.001) and less strongly with HIV-RNA levels (rs = 0.173) and CD4(+) counts (rs = -0.182, both p < 0.05). After ART, phe/tyr dropped to 0.72 +/- 0.16 (=-27%; U= 5.21, p = 0.01) which was due to an average decline of -14% of phe concentrations from 73.1 +/- 34.0 mu mol/L at baseline to 62.9 +/- 17.8 mu mol/L after ART (U = 2.51, p = 0.01) and a concomitant increase of tyr concentrations (+13%, U = 2.46, p = 0.01). In parallel, significant reductions of plasma and urine neopterin concentrations were observed during ART. Conclusions: Increased phe/tyr is frequent in patients with HIV-1 infection and is related to immune activation. ART was found to decrease phe/tyr and this change could indicate and influence on PAH activity. Future studies might be able to show whether the decline of phe/tyr under ART may concur with the often improved neuropsychiatric status in treated patients. (C) 2009 Elsevier Inc. All rights reserved.