Improvement of immune functions in HIV infection by sulfur supplementation: Two randomized trials

Abstract

To determine the therapeutic effect of sulfur amino acid supplementation in HIV infection we randomized 40 patients with antiretroviral therapy (ART; study 1) and 29 patients without ART (study 2) to treatment for 7 months with N-acetyl-cysteine or placebo at an individually adjusted dose according to a defined scheme. The main outcome measures were the change in immunological parameters including natural killer (NK) cell and T cell functions and the viral load. Both studies showed consistently that N-acetyl-cysteine causes a marked increase in immunological functions and plasma albumin concentrations. The effect of N-acetyl-cysteine on the viral load, in contrast, was not consistent and may warrant further studies. Our findings suggest that the impairment of immunological functions in HIV+ patients results at least partly from cysteine deficiency. Because immune reconstitution is a widely accepted aim of HIV treatment, N-acetyl-cysteine treatment may be recommended for patients with and without ART. Our previous report on the massive loss of sulfur in HIV-infected subjects and the present demonstration of the immunoreconstituting effect of cysteine supplementation indicate that the HIV-induced cysteine depletion is a novel mechanism by which a virus destroys the immune defense of the host and escapes immune elimination.

Glutathione and immune function

“…Both studies consistently showed that treatment of these patients with the additional source of cysteine caused a significant enhancement of several immunological functions under test, including restoration of natural killer cell activity to almost normal levels (Breitkreutz et al 2000b). Currently, there are no follow-up data available.…”

“…In view of the enormous variability of cysteine catabolism in HIV-infected patients, the individual dose in the two placebo-controlled trials was adjusted according to individual needs (Breitkreutz et al 2000b). Advantage was taken of the fact that treatment with N-acetyl-cysteine also increases the otherwise abnormally low plasma glutamine levels.…”

Chronic elevation of plasma thioredoxin: Inhibition of chemotaxis and curtailment of life expectancy in AIDS

“…Because NAC is a source of cysteine, the amino acid that limits GSH synthesis, and because NAC can also act directly to relieve oxidative stress, these findings indicate that increasing intracellular GSH and͞or decreasing oxidative stress in vitro decreases Trx release. This finding suggests that the release of Trx into plasma in HIV-infected subjects may be related to the low GSH levels that occur in many of these subjects (29) and hence that NAC treatment, which raises GSH in such subjects (27,30), might decrease plasma Trx.…”

Genetics, FACS, Immunology, and Redox: A Tale of Two Lives Intertwined

“…The Heidelberg group extended this finding by showing, in their placebocontrolled studies with HIV patients, that NAC treatment improves the in vitro function of T cells taken from these patients (75). In the placebo-controlled trial that we conducted sometime before, we demonstrated that NAC treatment replenishes GSH in HIV-infected people (76).…”