A Pilot Study of Oral B Vitamin Therapy for Asymptomatic or Mildly Symptomatic Hyperlactatemia in Patients on NRTIs

Hyperlactatemia, with or without lactic acidosis, is a potentially life-threatening condition that appears to be associated with NRTI therapy. The natural history of lactate elevation as a complication of NRTI therapy is not clearly understood; however, some patients receiving these therapies experience a progressive increase in lactate to symptomatic levels. Deficiencies in thiamine (vitamin B1) and riboflavin (vitamin B2) have been implicated as cofactors in producing hyperlactatemia and lactic acidosis in NRTI-treated patients. A nontoxic intervention that could prevent or reverse advancing lactic acidosis and preserve NRTI use would be highly desirable. To date, no controlled studies have been done to examine the potential role of dietary intake, B vitamin deficiency, and B vitamin therapy on the pathogenesis and clinical course on NRTI-associated lactic acidosis. The hypothesis proposed is that high-dose vitamin B treatment can normalize elevated lactate levels among NRTI-exposed individuals with moderately elevated lactate levels.

This study consists of 2 steps: Step 1 (screening) and Step 2 (treatment). Patients are screened during Step 1 for sustained hyperlactatemia and Step 2 eligibility. Patients with sustained hyperlactatemia but no symptoms that indicate high risk of progression to lactic acidosis and with no plans to change existing NRTI-containing antiretroviral therapy may enter Step 2. A fasting, nonexercise, venous lactate level is obtained at Step 2 entry for use as a baseline measurement, and every patient receives high-dose oral vitamin B1 and B2 therapy for 4 weeks. Fasting, nonexercise, venous lactate levels are measured at Weeks 1, 2, and 4 to observe the kinetics of changes in lactate levels on study treatment.