Progression of fibrosis in HIV and hepatitis C virus-coinfected patients treated with interferon plus ribavirin-based therapy: analysis of risk factors.
BACKGROUND
We determined the prevalence and determinants of worsening fibrosis in patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) who were receiving anti-HCV therapy.


METHODS
Among 383 HIV-HCV-coinfected patients who received at least 1 dose of anti-HCV treatment (weekly subcutaneous injections of 1.5 mug/kg pegylated interferon-alpha-2b plus daily ribavirin or thrice-weekly subcutaneous injections of 3 MU of interferon-alpha-2b plus daily ribavirin for 48 weeks), paired pretreatment and posttreatment liver biopsy specimens were available and interpretable for 198 cases. Hepatic necroinflammation and fibrosis were graded with Ishak's classification. Histological worsening of fibrosis was defined as a score increase of > or =2 points in patients with fibrosis stage of <4 and as a score increase of 1 point in patients with stage-5 fibrosis.


RESULTS
The mean interval +/- standard deviation between the 2 biopsies was 109 +/- 34 weeks. Fibrosis worsened in 34 patients (17.1%). In univariate analysis, ongoing antiretroviral therapy, failure to achieve a sustained viral response, nucleoside reverse-transcriptase inhibitor therapy, didanosine therapy, and stavudine therapy were significantly associated with worsening of fibrosis. Didanosine (odds ratio, 3.34; 95% confidence interval, 1.39-7.96; P = .007) and failure to have a sustained viral response (odds ratio, 9.05; 95% confidence interval, 2.06-39.66; P = .003) remained significantly associated with worsening of fibrosis.


CONCLUSIONS
The mitochondrial toxicity of antiretrovirals, such as didanosine, seems to play a major role in worsening of fibrosis during HCV therapy. Therefore, anti-HCV therapy should ideally be administered before antiretroviral treatment initiation. If anti-HCV and anti-HIV treatments have to be administered concomitantly, then nucleoside reverse-transcriptase inhibitors with the lowest mitochondrial toxicity should be preferred.
Bani-Sadr
Firouzé
F
Groupe Hospitalier Universitaire Est, Université Paris 6, INSERM U707, France. firouze.bani-sadr@tnn.ap-hop-paris.fr
Lapidus
Nathanael
N
Bedossa
Pierre
P
De Boever
Corinne Merle
CM
Perronne
Christian
C
Halfon
Philippe
P
Pol
Stanislas
S
Carrat
Fabrice
F
Cacoub
Patrice
P
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use* / Q000633:toxicity; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D007372:Interferons / Q000008:administration & dosage / Q000627:therapeutic use*; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000453:epidemiology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects; D015995:Prevalence; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use*; D012307:Risk Factors
D019380:Anti-HIV Agents; D012254:Ribavirin; D007372:Interferons