Decrease of elevated N,N-dimethylglycine and N-methylglycine in human immunodeficiency virus infection during short-term highly active antiretroviraltherapy

This study investigates fasting serum levels of methionine and related meta bolites, vitamin B-6, and folate during highly active antiretroviral therap y in therapy-naive human immunodeficiency virus (HIV)-1-infected outpatient s. The research design consisted of before and during therapy measurements with a median treatment period of 100 days (range, 50 to 188) in frozen sam ples. The subjects included 17 consecutive HIV-1-infected outpatients (15 m en and 2 women; 25 to 65-years-old). Controls were 42 healthy individuals ( 28 men and 14 women; 24- to 82-years-old) without serologic evidence of HIV and/or hepatitis C infection and normal clinical chemistry. Subjects recei ved treatment with the reverse transcriptase inhibitors, azidothymidine (AZ T) or stavudine (D4T) plus lamivudine (3TC) and either the protease inhibit ors, indinavir (IND), nelfinavir (NELF), ritonavir (RITV), or saquinavir (S AQ) at the standard dosage. Serum concentrations of methionine, total homoc ysteine (tHcy), cystathionine (CYSTA), N,N-dimethylglycine (DMG), N-methylg lycine (MG), methylmalonic acid (MMA), and total cysteine, as well as vitam in B-6, folate, and soluble tumor necrosis factor receptor p75 were taken a t baseline and during highly active antiretroviral therapy. Baseline, serum tHcy, MMA, CYSTA, vitamin B-6 concentrations were not significantly differ ent from healthy controls. There was, however, a trend towards lower folate serum concentrations at baseline in HIV-infected patients as compared with healthy controls (P = .06). There were no significant correlations between tHcy and vitamin B-6, folate, or MMA. Elevated baseline levels of DMG and MG decreased significantly during antiretroviral therapy (P = .0019 and .04 , respectively), whereas no significant changes in serum concentrations of CYSTA, MMA, or methionine were detected. tHcy increased in 12 of 17 patient s (P = .09). HIV-infected patients displayed significant alterations (eleva ted DMG and MG serum concentrations) in metabolite levels of the betaine pa thway in methionine metabolism, which might be positively influenced by new ly initiated antiretroviral combination therapy. Copyright (C) 2001 by W.B. Saunders Company.