By Liz Highleyman

Numerous studies have indicated that HIV-HCV coinfected patients experience more rapid liver disease progression and do not respond as well to interferon-based treatment for hepatitis. Further, some data have elucidated the biological mechanisms underlying these differences.

The picture is complicated, however, by the fact that several other studies have failed to observe similar differences in disease progression or treatment response, including 2 presented at the 58th Annual Meeting of the American Association for the Study of Liver Diseases in Boston (November 2-6, 2007).

Liver Disease Progression

In the first study, researchers assessed mortality and liver-related complications in a prospective cohort of inner-city injection drug users with chronic hepatitis C followed at an urban county hospital and a veterans’ hospital. A total of 350 patients were enrolled beginning in 1997, and have been followed for about 5 years on average. About half (176 patients; 49.7%) were coinfected with HIV and HCV, while the remainder had chronic HCV infection alone.

Causes of death were determined by the investigators, and were attributed to HIV, end-stage liver disease (ESLD), or illicit drug use only when this was unequivocal. Liver cirrhosis was defined by histology or overt clinical or radiological evidence.

Results

• Overall, 48 HIV-HCV coinfected patients and 34 HCV monoinfected patients died during follow-up.

• Coinfected patients did not have a statistically significant increase in mortality compared with the group overall (OR 1.54; P = 0.09).

• Similar proportions of HIV-HCV coinfected and HCV monoinfected patients developed liver cirrhosis (16% vs 18%; P = non-significant).

• Use of HAART was not protective against death among the coinfected patients.

• 71% of coinfected patients who died had regularly received HAART, while 29% had not (P = non-significant).

Clinical Outcomes

Conclusion

“HIV-HCV coinfected and HCV monoinfected patients, when followed prospectively, have similar rates of death or cirrhosis,” the researchers concluded.

“End-stage liver disease and HIV are competing causes of death in coinfected patients,” they continued. “Reported high rates of ESLD-associated death in coinfected patients alive today should be interpreted with caution, and compared to those in similar groups of HCV monoinfected patients.”

Finally, they stated, “As the HAART era continues, morbidity and mortality in HIV positive patients may approach that of their HIV negative counterparts.”

Response to Treatment

In the second presentation, investigators revisited data from the pivotal APRICOT trial, looking at the relationship between early response to interferon-based therapy and sustained virological response (SVR) in HIV-HCV coinfected patients, and comparing these results to data from HCV monoinfected individuals.

APRICOT included 868 HCV-HIV coinfected patients in 19 countries with compensated liver disease, stable HIV disease, and a CD4 count above 100 cells/mm³. Participants were randomly assigned to receive conventional interferon plus 800 mg/day ribavirin, pegylated interferon alfa-2a (Pegasys) plus placebo, or pegylated interferon plus ribavirin for 48 weeks (it is now recognized that 1000-1200 mg/day weight-based ribavirin is superior to the fixed 800 mg/day dose). The SVR rate was highest in the pegylated interferon plus ribavirin arm: 40% overall, 29% for patients with HCV genotype 1, and 62% for those with genotypes 2/3.

The present analysis included all APRICOT participants from the pegylated interferon/ribavirin arm infected with HCV genotype 1, 2, or 3. SVR rates were determined as a function of response to therapy at weeks 4 and 12.

Rapid virological response (RVR) was defined as undetectable HCV RNA (< 50 IU/mL) at week 4. Complete early virological response (cEVR) was defined as lack of RVR but undetectable HCV RNA at week 12, while partial early virological response (pEVR) was defined as lack of RVR but ≥ 2 log reduction in HCV RNA from baseline (though still detectable) at week 12. SVR was defined as undetectable HCV RNA 24 weeks after completion of therapy.

Results

• Data from 271 patients were included (see table).

• SVR rates for HCV genotype 1 and genotypes 2/3 were greatest in patients achieving RVR (81.8% for genotype 1 and 94.3% for genotypes 2/3), followed by cEVR (63.2% and 69.7%, respectively), and then pEVR.

• Patients not achieving RVR, cEVR, or pEVR had a minimal chance of achieving SVR.

• Considering only patients with pEVR, SVR rates were influenced by several baseline and treatment factors, indicating that response in this subgroup of patients is variable.

“Coinfected patients who achieve an RVR have a similarly high chance as [HCV] monoinfected patients of achieving an SVR irrespective of genotype,” the researchers concluded. “Patients that achieve cEVR also have similarly high rates of SVR as in monoinfected patients. As in monoinfected patients, RVR is the strongest predictor for SVR, but in addition achieving a cEVR is also highly predictive of achieving an SVR.”

Fundación de Investigación de Diego, Santurce, PR; University of California, San Diego, CA; University of Bonn, Bonn, Germany; Roche, Nutley, NJ; Universita Degli Studi di Brescia, Brescia, Italy; Mount Sinai School of Medicine, New York, NY.

11/27/07

References

A Monto, S Currie, LM Dove, and others. HIV-HCV coinfection: similar rates of cirrhosis and death than HCV alone, outcomes not averted by HAART. AASLD 2007. Abstract 138.