N-acetylcysteine replenishes glutathione in HIV infection.
BACKGROUND
Glutathione (GSH) deficiency is common in HIV-infected individuals and is associated with impaired T cell function and impaired survival. N-acetylcysteine (NAC) is used to replenish GSH that has been depleted by acetaminophen overdose. Studies here test oral administration of NAC for safe and effective GSH replenishment in HIV infection.


METHODS
Oral NAC administration in a randomized, 8-week double-blind, placebo-controlled trial followed by optional open-label drug for up to 24 weeks.


METHODS
HIV-infected, low GSH, CD4 T cells < 500 micro L(-1), no active opportunistic 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 NAC-treated subjects to 89% of uninfected controls (P = 0.03). Baseline GSH levels in the placebo group (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 levels, also increased in the NAC-treated subjects (P = 0.04). Adverse effects were minimal and not significantly associated with NAC ingestion.


CONCLUSIONS
NAC treatment for 8 weeks safely replenishes whole blood GSH and T cell GSH in HIV-infected individuals. Thus, NAC offers useful adjunct therapy to increase protection against oxidative stress, improve immune system function and increase detoxification of acetaminophen and other drugs. These findings suggest that NAC therapy could be valuable in other clinical situations in which GSH deficiency or oxidative stress plays a role in disease pathology, e.g. rheumatoid arthritis, Parkinson's disease, hepatitis, liver cirrhosis, septic shock and diabetes.
De Rosa
S C
SC
Department of Genetics, Stanford University, USA.
Zaretsky
M D
MD
Dubs
J G
JG
Roederer
M
M
Anderson
M
M
Green
A
A
Mitra
D
D
Watanabe
N
N
Nakamura
H
H
Tjioe
I
I
Deresinski
S C
SC
Moore
W A
WA
Ela
S W
SW
Parks
D
D
Herzenberg
L A
LA
Herzenberg
L A
LA
D000111:Acetylcysteine / Q000008:administration & dosage*; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage*; D018450:Disease Progression; D004311:Double-Blind Method; D005978:Glutathione / Q000097:blood*; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality; D006801:Humans; D008297:Male; D016019:Survival Analysis
D000998:Antiviral Agents; D005978:Glutathione; D000111:Acetylcysteine