N-acetylcysteine replenishes glutathione in HIV infection

Background Glutathione (GSH) deficiency is common in HIV-infected individua ls and is associated with impaired T cell function and impaired survival. N -acetylcysteine (NAC) is used to replenish GSH that has been depleted by ac etaminophen overdose. Studies here test oral administration of NAC for safe and effective GSH replenishment in HIV infection. Design Oral NAC administration in a randomized, 8-week double-blind, placeb o-controlled trial followed by optional open-label drug for up to 24 weeks. Subjects HIV-infected, low GSH, CD4 T cells < 500 <mu>L-1, no active opport unistic infections or other debilitation; n = 81. Study conducted prior to introduction of protease inhibitors. Results Whole blood GSH levels in NAC arm subjects significantly increased from 0.88 mM to 0.98 mM, bringing GSH levels in NAG-treated subjects to 89% of uninfected controls (P = 0.03). Baseline GSH levels in the placebo grou p (0.91) remained essentially the same during the 8 week placebo-controlled trial. T cell GSH, adjusted for CD4 T cell count and beta2-microglobulin l evels, also increased in the NAG-treated subjects (P = 0.04). Adverse effec ts were minimal and not significantly associated with NAC ingestion. Conclusion. NAC treatment for 8 weeks safely replenishes whole blood GSH an d T cell GSH in HIV-infected individuals. Thus, NAC offers useful adjunct t herapy to increase protection against oxidative stress, improve immune syst em function and increase detoxification of acetaminophen and other drugs. T hese findings suggest that NAC therapy could be valuable in other clinical situations in which GSH deficiency or oxidative stress plays a role in dise ase pathology, e.g. rheumatoid arthritis, Parkinson's disease, hepatitis, l iver cirrhosis, septic shock and diabetes.