Risk factors for symptomatic mitochondrial toxicity in HIV/hepatitis C virus-coinfected patients during interferon plus ribavirin-based therapy.
OBJECTIVE
To evaluate the incidence, clinical features, and risk factors for symptomatic mitochondrial toxicity in HIV/hepatitis C virus (HCV)-coinfected patients receiving anti-HCV therapy.


METHODS
All cases of symptomatic mitochondrial toxicity reported in 416 patients participating in an open, randomized trial of peg-interferon alpha-2b plus ribavirin vs. interferon alpha-2b plus ribavirin for 48 weeks were reviewed. Associations with antiretroviral treatments and with clinical and laboratory findings were sought by univariate and multivariate analysis.


RESULTS
Eleven of the 383 patients who received at least 1 dose of anti-HCV treatment developed symptomatic mitochondrial toxicity (symptomatic hyperlactatemia and pancreatitis in 6 and 5 patients, respectively). All cases occurred in patients being treated for HIV infection, and the incidence of symptomatic mitochondrial toxicity was 47.5 per 1000 patient-years. In multivariate analysis, symptomatic mitochondrial toxicity was significantly associated with didanosine-containing antiretroviral regimens (odds ratio 46; 95% CI, 7.4 to infinity; P < 0.001), but not with stavudine or with nucleoside reverse transcriptase inhibitor regimens not containing didanosine. The incidence of symptomatic mitochondrial toxicity was 200.2 per 1000 patient-years in patients receiving didanosine. Demographic characteristics were not associated with symptomatic mitochondrial toxicity.


CONCLUSIONS
Coadministration of ribavirin with didanosine should be avoided. If unavoidable, patients should be monitored closely for mitochondrial toxicity. Didanosine should be suspended if clinical signs or symptoms of mitochondrial toxicity occur.
Bani-Sadr
Firouzé
F
Groupe Hospitalier Universitaire Est, Université Paris 6, INSERM U444, France. firouze.bani-sadr@tnn.ap-hop-paris.fr
Carrat
Fabrice
F
Pol
Stanislas
S
Hor
Ravy
R
Rosenthal
Eric
E
Goujard
Cécile
C
Morand
Patrice
P
Lunel-Fabiani
Françoise
F
Salmon-Ceron
Dominique
D
Piroth
Lionel
L
Pialoux
Gilles
G
Bentata
Michèle
M
Cacoub
Patrice
P
Perronne
Christian
C
D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D006943:Hyperglycemia / Q000139:chemically induced; D007279:Injections, Subcutaneous; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects; D015999:Multivariate Analysis; D010195:Pancreatitis / Q000139:chemically induced; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012189:Retrospective Studies; D012254:Ribavirin / Q000009:adverse effects* / Q000627:therapeutic use; D012307:Risk Factors; D016896:Treatment Outcome
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b