Effect of L-carnitine on human immunodeficiency virus-1 infection-associated apoptosis: a pilot study

Blood. 1998 May 15;91(10):3817-24.


The Fas/Fas ligand system is involved in uncontrolled apoptosis, which ultimately leads to the loss of T lymphocytes in human immunodeficiency virus (HIV)-infected individuals. The signal transduced by Fas receptor involves the activation of an acidic sphingomyelinase, sphingomyelin breakdown, and ceramide production. Our recent reports have shown that L-carnitine inhibits Fas-induced apoptosis and ceramide production both in vitro and in vivo. The aim of this study was to study, in a preliminary fashion, the impact of long-term L-carnitine administration on CD4 and CD8 absolute counts, rate, and apoptosis in HIV-1-infected subjects. The generation of cell-associated ceramide and HIV-1 viremia was also investigated. Eleven, asymptomatic, HIV-1-infected subjects, who refused any antiretroviral treatment despite experiencing a progressive decline of CD4 counts, were treated with daily infusions of L-carnitine (6 g) for 4 months. Immunologic and virologic measures and safety were monitored at the start of the treatment and then on days 15, 30, 90, and 150. L-carnitine therapy resulted in an increase of absolute CD4 counts, which was statistically significant on day 90 and 150 (P = . 010 and P = .019, respectively). A positive, not significant trend was also observed even in the change in absolute counts of CD8 lymphocytes. L-carnitine therapy also led to a drop in the frequency of apoptotic CD4 and CD8 lymphocytes. This reduction occurred gradually, but changes in actual values between each time point and baseline were strongly significant (P = .001 at the end of the study compared with the baseline). A strong reduction (P = .001) in cell-associated ceramide levels was found at the end of the study. In general, HIV-1 viremia increased slightly. No toxicity related to L-carnitine therapy was observed and dose reductions were not necessary. In HIV-1-infected subjects, long-term infusions of L-carnitine produced substantial increases in the rate and absolute counts of CD4 and, to a lesser degree, of CD8 lymphocytes. This was paralleled by a reduced frequency of apoptotic cells of both subgroups and a decline in the levels of ceramide. No clinically relevant change of HIV-1 viremia was observed.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Apoptosis / drug effects*
  • CD4-Positive T-Lymphocytes / drug effects*
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / pathology
  • CD8-Positive T-Lymphocytes / drug effects*
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / pathology
  • Carnitine / pharmacology*
  • Carnitine / therapeutic use
  • Ceramides / biosynthesis
  • Fas Ligand Protein
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • HIV Infections / pathology
  • HIV-1*
  • Humans
  • Lymphocyte Count / drug effects
  • Male
  • Membrane Glycoproteins / drug effects*
  • Membrane Glycoproteins / physiology
  • Pilot Projects
  • Safety
  • Signal Transduction / drug effects
  • Substance Abuse, Intravenous / complications
  • Treatment Outcome
  • Viremia / drug therapy*
  • Viremia / pathology
  • fas Receptor / physiology*


  • Ceramides
  • FASLG protein, human
  • Fas Ligand Protein
  • Membrane Glycoproteins
  • fas Receptor
  • Carnitine