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 micromol/micromol. 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 micromol/L at baseline to 62.9+/-17.8 micromol/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.
Zangerle
Robert
R
HIV Unit, Department of Dermatology and Venerology, Innsbruck Medical University, Innsbruck, Austria.
Kurz
Katharina
K
Neurauter
Gabriele
G
Kitchen
Maria
M
Sarcletti
Mario
M
Fuchs
Dietmar
D
D000368:Aged; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy* / Q000276:immunology; D015497:HIV-1; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D019798:Neopterin / Q000097:blood / Q000652:urine; D010649:Phenylalanine / Q000097:blood* / Q000652:urine; D010651:Phenylalanine Hydroxylase / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics; D014443:Tyrosine / Q000097:blood* / Q000652:urine
D012367:RNA, Viral; D014443:Tyrosine; D010649:Phenylalanine; D019798:Neopterin; D010651:Phenylalanine Hydroxylase