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

Brain Behav Immun. 2010 Mar;24(3):403-8. doi: 10.1016/j.bbi.2009.11.004. Epub 2009 Nov 16.


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.

MeSH terms

  • Aged
  • Antiretroviral Therapy, Highly Active*
  • CD4-Positive T-Lymphocytes
  • Female
  • HIV Infections / blood*
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • HIV-1*
  • Humans
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Neopterin / blood
  • Neopterin / urine
  • Phenylalanine / blood*
  • Phenylalanine / urine
  • Phenylalanine Hydroxylase / metabolism
  • RNA, Viral / genetics
  • Tyrosine / blood*
  • Tyrosine / urine


  • RNA, Viral
  • Tyrosine
  • Phenylalanine
  • Neopterin
  • Phenylalanine Hydroxylase