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l-Carnitine for the treatment of highly active antiretroviral therapy-related hypertriglyceridemia in HIV-infected adults

Loignon, Maude; Toma, Emil

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In HIV-infected individuals, hypertriglyceridemia was first reported in the absence of antiretroviral therapy, and was probably dependent on the unregulated production of cytokines such as IFN-α or tumour necrosis factor alpha [1]. Among patients receiving highly active antiretroviral therapy (HAART), approximately 60–70% eventually develop hypertriglyceridemia, often associated with a complex syndrome of lipodystrophy, central adiposity and insulin resistance [2]. Moreover, pancreatitis and premature cardiovascular complications have been reported in HIV-infected patients with HAART-related hypertriglyceridemia [3,4].

Several therapeutic approaches to HIV- or HAART-related hypertriglyceridemia have been suggested or evaluated in small groups of patients. In AIDS patients, in the absence of antiretroviral therapy, l-carnitine treatment resulted in a strong reduction of serum triglyceride levels [5]. This was explained by the effect of l-carnitine on tumour necrosis factor alpha modulation. In patients with HAART-related hypertriglyceridemia, low l-carnitine doses (2 g/day) for 12 weeks had no significant effect on triglyceride levels but a trend was noted for decreased cholesterol levels [6]. Favourable results have been reported for gemfibrozil [7], bezafibrate [8], and fenofibrate [9]. On the other hand, the statins infrequently normalized cholesterol and triglyceride levels in patients with protease-inhibitor-related hyperlipidemia and might have increased hepatic toxicity [10].

We conducted a prospective open trial in 16 adults (one woman, 15 men) aged 44.1 ± 9.3 years, with HIV infection known for 8.8 ± 3.8 years (range 2–14), who had been receiving antiretroviral agents for 7.2 ± 2.8 years (range 2–12). Their ongoing HAART included at least one protease inhibitor in all but one patient. l-Carnitine, 3 g a day, was administered orally for 8.9 ± 5 months (range 2.3–19). Fasting serum triglyceride levels, cholesterol, glucose, C-peptide, other metabolic and biochemical parameters, CD4 cell counts and HIV-RNA levels were measured at 1–2 month intervals. Baseline data were compared with results at month 1, month 2, at the first change of HAART (after initiating l-carnitine therapy), and at the end of therapy or the time of data analysis. Changes in mean triglyceride, cholesterol and glucose levels from baseline were analysed using Student's t-test; a two-sided P value less than 0.05 was considered significant.

At baseline, the viral load was 3.4 ± 1.5 logs (range < 1.7–5.27) HIV-1-RNA copies/ml, and the median CD4 cell count was 218 ± 210 cells/ml (range 0–670). Mean baseline triglyceride levels were 5.67 ± 1.78 mmol/l (range 2.28–8.74; normal 0.5–2.0), cholesterol levels were 5.6 ± 1.58 mmol/l (range 3.43–8.07; normal 2–5.2), and glucose levels were 5.3 ± 0.93 mmol/l (range 3.7–7.4; normal 3.6–6.1).

In comparison with baseline values, during l-carnitine therapy, triglyceride levels were decreased by 39% at month 1, by 28% at month 2, by 23% when HAART was first changed, and by 34.7% at the last measurement (Table 1). The reduction in triglyceride levels was statistically significant at every time-point. A normal triglyceride level of 2.3 mmol/l or less was recorded in 15% of patients after 2 months of therapy, and in 40% of patients at the last evaluation. However, near-normal triglyceride levels (≤ 3 mmol/l) were obtained in 54% of patients after 2 months of treatment, and in 69% at the last assessment. No significant effect was noted for cholesterol (Table 1) and C-peptide in this group of patients.

Table 1
Table 1:
Effects of l-carnitine on triglyceride and cholesterol levels.

The role of carnitine in the regulation of fatty acid and carbohydrate metabolism is very complex. It is an essential co-factor for the transfer of fatty acyl groups into the mitochondrial matrix, where they undergo beta-oxidation [11]. Carnitine also plays a role in the transfer of acetyl and other short acyl groups from peroxisomes to mitochondria for further oxidation [11].

In conclusion, in this pilot trial, l-carnitine at a daily dose of 3 g significantly decreased serum triglyceride levels in HIV-infected adults with HAART-related hypertriglyceridemia. Although no significant effect was noted on other metabolic abnormalities in this group of patients, l-carnitine may fulfill a role in the management of HAART-related hypertriglyceridemia. Data from this pilot work helped in the design of a randomized, comparative, multicentre trial, now in preparation.

Acknowledgement

The authors would like to thank Mr Ovid Da Silva for editing this manuscript.

Maude Loignon

Emil Toma

References

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© 2001 Lippincott Williams & Wilkins, Inc.