AIDSWEEKLY Plus; Monday, June 8 & 15, 1998
Daniel J. DeNoon, Senior Editor
Eight of the 11 patients in the study had increased CD4 counts after four months of the treatment. No toxicities occurred.
The fact that the increases occurred despite increased HIV viremia suggest that the agent, L-carnitine, may be a useful adjunct to highly active antiretroviral therapy (HAART). Clinical trials investigating this possibility are underway, according to an Italian research team.
"Our results indicate that L-carnitine targets the immune system and suggest that complementing antiretroviral therapy with L-carnitine may be an attractive approach to the management of HIV-1 infected patients," wrote Sonia Moretti of La Sapienza University, Rome, Italy, and colleagues.
Moretti et al. reported their findings in the journal Blood ("Effect of L-Carnitine on Human Immunodeficiency Virus-1 Infection- Associated Apoptosis: A Pilot Study," Blood, 1998;91(10):3817-24).
The researchers based their trial on laboratory evidence that the T-cell decline characteristic to AIDS is largely due to uncontrolled, HIV-accelerated apoptosis, or programmed cell death. The in vitro data suggest that the molecular mechanism of this apoptosis involves a signal (sent via the surface Fas receptor) that tells the cell to produce ceramide, which mediates apoptosis. Ceramide also enhances HIV-1 replication.
A preliminary clinical study showed that L-carnitine could reduce the frequency of apoptotic CD4(+) and CD8(+) T cells - and reduce cell-associated ceramide - in AIDS patients.
The 11 patients, all members of a long-term drug addiction rehabilitation community, received daily infusions of 6 grams of L- carnitine for four months.
At entry the patients had a median baseline CD4 count of 331 cells/(micro)L which increased to 476 cells/(micro)L on day 150. There was a smaller, statistically nonsignificant increase in CD8(+) counts. Also seen was a strongly significant reduction in the frequency of apoptotic CD4(+) and CD8(+) lymphocytes and in cell- associated ceramide levels.
"Taken together, our data suggest that long-term L-carnitine administration may have a substantial impact on the chief immunologic abnormality associated with HIV-1 infection, the loss of CD4 T cells, through downmodulating the generation of ceramide and reducing the rate of apoptotic lymphocyte death," Moretti et al. wrote.
"Indeed, L-carnitine administration, although not affecting the viral life cycle, interrupts the HIV infection-associated ceramide generation and consequently the lymphocyte apoptosis, which is considered a crucial factor in the pathogenesis of AIDS."
The authors reported no adverse effects from L-carnitine treatment.
The corresponding author for this study is Claudo De Simone, Department of Experimental Medicine, Via Vetoio 10, Coppito 2, 67100 L'Aquila, Italy.
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