EFFECT OF L-CARNITINE ON HUMAN IMMUNODEFICIENCY VIRUS-1 INFECTION-ASSOCIATED APOPTOSIS - A PILOT-STUDY

The Fas/Fas ligand system is involved in uncontrolled apoptosis, which ultimately leads to the loss of T lymphocytes in human immunodeficien cy virus (HIV)-infected individuals. The signal transduced by Fas rece ptor involves the activation of an acidic sphingomyelinase, sphingomye lin breakdown, and ceramide production. Our recent reports have shown that L-carnitine inhibits Fas-induced apoptosis and ceramide productio n 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 administratio n on CD4 and CD8 absolute counts, rate, and apoptosis in HIV-1-infecte d subjects. The generation of cell-associated ceramide and HIV-1 virem ia was also investigated. Eleven, asymptomatic, HIV-1-infected subject s, who refused any antiretroviral treatment despite experiencing a pro gressive 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 1 5, 30, 90, and 150. L-carnitine therapy resulted in an increase of abs olute CD4 counts, which was statistically significant on day 90 and 15 0 (P = .010 and P = .019 respectively). A positive, not significant tr end was also observed even in the change in absolute counts of CD8 lym phocytes. L-carnitine therapy also led to a drop in the frequency of a poptotic CD4 and CD8 lymphocytes. This reduction occurred gradually, b ut changes in actual values between each time point and baseline were strongly significant (P = .001 at the end of the study compared with t he baseline). A strong reduction (P = .001) in cell-associated ceramid e levels was found at the end of the study. In general, HIV-1 viremia increased slightly. No toxicity related to L-carnitine therapy was obs erved and dose reductions were not necessary. In HIV-1-infected subjec ts, 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 cl inically relevant change of HIV-1 viremia was observed. (C) 1998 by Th e American Society of Hematology.