www.hivandhepatitis.com

ICAAC 2011: Didanosine, Higher HCV Viral Load Predict Liver Fibrosis in HIV/HCV Coinfected People

Use of didanosine (ddI, Videx) -- along with higher hepatitis C virus (HCV) RNA level, male sex, and older age -- was a significant risk factor for liver fibrosis in people with HIV/HCV coinfection, researchers reported at the 51st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2011) this week in Chicago.

HIV positive people coinfected with hepatitis C tend to experience more rapid liver disease progression than those with HCV alone. Weakened immune function is thought to contribute to this disparity, but other factors may also play a role. Certain antiretroviral drugs are known to cause liver toxicity, but their effects on fibrosis progression has not been extensively studied.

In the present analysis, Spanish researchers looked at factors contributing to fibrosis progression as assessed by transient elastometry (FibroScan), a non-invasive method that uses sound waves to measures liver stiffness.

The study included 213 adult Caucasian HIV patients, 111 of whom also had hepatitis C. People reporting heavy alcohol consumption (> 50 g/day), those with hepatitis B virus (HBV) coinfection or non-infectious liver diseases, and those with < 75% adherence to antiretroviral therapy (ART) were excluded.

Results

• In a univariate analysis, several factors were associated with increased liver fibrosis:
  • Use of didanosine;
  • Use of stavudine (d4T, Zerit);
  • Amount of time on ART;
  • Duration of HIV infection;
  • Duration of HCV infection;
  • Higher HIV viral load;
  • Higher HCV viral load;
  • Presence of lipodystrophy;
  • Male sex;
  • Older age;
  • Low current CD4 T-cell count;
  • Low nadir (lowest-ever) CD4 count.
  • Smaller CD4 cell gains after starting ART;
  • Higher blood levels of matrix metalloproteases 2 (MMP-2) and its tissue inhibitor TIMP-2.
• No association was seen with other specific antiretroviral drugs.
• In a multivariate logistic regression controlling for other factors, the only remaining significant predictors of fibrosis progression were:
  • Use of didanosine (nearly 8 times higher risk);
  • HCV viral load (about 3.5 times higher risk);
  • Male sex;
  • Older age.

Didanosine is known to cause mitochondrial toxicity, which can manifest as liver steatosis, or fat accumulation. This study suggests that didanosine may also contribute to liver fibrosis. The association between fibrosis and HCV RNA level is also interesting, since most research indicates that HCV viral load is not closely linked to disease progression, as is the case with HIV.

Investigator affiliations: Hosp Central de Asturias, Oviedo Univ Medical School, Oviedo, Spain; Hosp. de Galdacano, Galdacano, Spain.

9/20/11

Reference

T Suarez-Zarracina, J Collazos, AH Montes, et al. Didanosine (ddi) Associated With Increased Liver Fibrosis In Adult HIV-infected Patients With/out HCV Coinfection. Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2011). Chicago, September 17-20, 2011. Abstract H3-811.