3rd International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV 23-26 October 2001, Athens, Greece

COULD ANTI-HEPATITIS C VIRUS TREATMENT WITH INTERFERON α AND RIBAVIRIN ENHANCE OR ENDURE LIOATROPHY IN PATIENTS PREVIOUSLY TREATED WITH ANTI-HIV MULTI THERAPY?

Antiviral Therapy 2001; 6(Suppl. 4):27 (abstract no. 35)

M Bentata, R Mansouri, P Honore and F Touam
SIDA Unit, Hospital AVICENNE, Bobigny, France

BACKGROUND: Combination therapy with interferon (IFN)2α pegylated (Peg) or not and ribavirin is increasing used in HIV-hepatitis C virus (HCV) co-infected patients on anti-HIV therapy. At this time, the anti-HIV therapies almost always comprise nucleoside reverse transcriptase inhibitors (NRTIs), which are considered the key factor in the pathogenesis of mitochondrial toxicity.

PATIENTS: We have observed seven patients who developed (3/7) or worsened (4/7) a peripheric lipoatrophy (LA) in the first months of anti-HCV treatment by IFN [1/7 pegIFN alone or associated with ribavirin (6/7)]. Four of seven were previously exposed to IP for a median time of 40 months (4-48) and 6/7 to NRTI for 45 months (28-54) probably to stavudine-didanosine for 30 months (4-54). Median weight loss (5/7) from the beginning of anti-HCV treatment to the apparition of LA was 5 kg, that is 8% of total body weight (0-10 kg, 0-15%). Weight loss was associated with impressive sunken cheeks, temples, eyes and limbs without fat repartition abnormalities. No consistent metabolic changes were observed. All of them presented with impressive fatigue and nausea. Three patients experienced hyperlactatemia (2.1-5.2 mmol/l), two polyneuropathies and one micro- and macrovacuolar steato-hepatitis. LA and other manifestations begin in the 3 months after the beginning of anti HCV treatment. LA did not regress after stopping IFN and ribavirin and switching NRTI but other clinical and biological abnormalities did slowly within 2 months. The most severe symptoms were observed in a patient on peg-IFN monotherapy.

DISCUSSION: Although a dose definition of lipodystrophies is not yet available, peripheral and severe facial fat wasting did not seem to be explained only by weight loss all the more because association with other symptoms commonly observed in mitochondrial dysfunction. As several studies have reported in vitro inhibition of mitochondrial mRNA by IFN, we hypothesize that IFN or pegINF (± ribavirin) could have acted synergistically with NRTI to develop lipoatrophy and mitochondrial toxicity.

CONCLUSIONS: Lipoatrophy with or without weight loss, constitutional symptoms, polyneuropathies, hepatitis and hyperlactatemia have been observed in the first 3 months of treatment with IFN (± ribavirin) in seven patients with previous well tolerated anti-HIV treatment comprising NRTL In the present context, the combination of INFα or pegIFN and ribavirin seems to be the best treatment, but as very limited data are available on tolerance of anti-HCV treatment in HIV infection clinicians must be aware of there possible side-effects and carefully monitor the markers of mitochondrial toxicity after initiation of anti-HCV treatment.

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