Virological and immunological effects of antioxidant treatment in patients with HIV infection.
BACKGROUND
Intracellular oxidative stress in CD4+ lymphocytes due to disturbed glutathione homeostasis may lead to impaired lymphocyte functions and enhanced HIV replication in patients with HIV infection, especially in those with advanced immunodeficiency. The aim of the present study was to assess whether short-term, high-dose antioxidant treatment might have effects on immunological and virological parameters in patients with HIV infection.


METHODS
In this pilot study, we examined virological and immunological effects of antioxidant combination treatment for 6 days with high doses of N-acetylcysteine (NAC) and vitamin C in 8 patients with HIV infection. The following were assayed before, during and after antioxidant treatment: HIV RNA plasma levels; numbers of CD4+, CD8+, and CD14+ leukocytes in blood; plasma thiols; intracellular glutathione redox status in CD4+ lymphocytes and CD14+ monocytes; lymphocyte proliferation; lymphocyte apoptosis and plasma levels of tumour necrosis factor (TNF)alpha; soluble TNF receptors and neopterin in plasma.


RESULTS
No significant changes in HIV RNA plasma levels or CD4+ lymphocyte counts in blood were noted during antioxidant treatment in the patient group. However, in the 5 patients with the most advanced immunodeficiency (CD4+ lymphocyte counts < 200 x 106 L(-1)), a significant rise in CD4+ lymphocyte count, a reduction in HIV RNA plasma level of 0.8 log, an enhanced lymphocyte proliferation and an increased level of intracellular glutathione in CD4+ lymphocytes were found. No change in lymphocyte apoptosis was noted.


CONCLUSIONS
Short-term, high-dose combination treatment with NAC and vitamin C in patients with HIV infection and advanced immunodeficiency lead to immunological and virological effects that might be of therapeutic value.
Müller
F
F
University of Oslo, The National Hospital, Rikshospitalet, Oslo, Norway. fredrik.muller@labmed.uio.no
Svardal
A M
AM
Nordoy
I
I
Berge
R K
RK
Aukrust
P
P
Frøland
S S
SS
D000111:Acetylcysteine / Q000008:administration & dosage* / Q000009:adverse effects; D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism*; D000328:Adult; D000975:Antioxidants / Q000008:administration & dosage* / Q000009:adverse effects; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D017209:Apoptosis / Q000276:immunology; D001205:Ascorbic Acid / Q000008:administration & dosage* / Q000009:adverse effects; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002455:Cell Division / Q000276:immunology; D003545:Cysteine / Q000097:blood; D004151:Dipeptides / Q000097:blood; D004359:Drug Therapy, Combination; D005978:Glutathione / Q000097:blood; D006801:Humans; D016753:Interleukin-10 / Q000097:blood; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D019798:Neopterin / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects; D010865:Pilot Projects; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D012995:Solubility; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000975:Antioxidants; D000998:Antiviral Agents; D004151:Dipeptides; D018950:Lipopolysaccharide Receptors; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; C028505:cysteinylglycine; D019798:Neopterin; D005978:Glutathione; D003545:Cysteine; D001205:Ascorbic Acid; D000111:Acetylcysteine