Background:  We examined the hypothesis that positive hepatitis C serostatus in HIV-infected patients indicates the presence of risk factors with considerable influence on survival, independent of the pathogenicity of the hepatitis C virus.

Methods:  The Danish HIV Cohort Study encompasses all HIV-infected patients treated in Danish HIV clinics. Of these, the 3026 patients living in Denmark at the time of HIV diagnosis, and born after 1951, were included as index patients. In the Danish Civil Registration System (DCRS), we identified 99 population controls per index patient, matched on gender, age, and council. For both HIV-infected index patients and population controls we identified all siblings and dates of death, emigration, or loss to follow-up in DCRS. Index siblings were classified according to hepatitis C virus (HCV) serostatus of the index patient. Cox’ regression analyses were used to estimate mortality rate ratios (MRR).

Results:  Of the index patients, 594 (20%) were HCV⁺, 2137 (71%) were HCV^­, and 295 (10%) were never tested for HCV. The 2 former groups had 450 and 1909 registered siblings, respectively. These index siblings provided 93,227 person-years; 120 (5.1%) died and 3.4% were lost to follow-up. The 332,344 control siblings provided 12,945,819 person-years with 10,677 fatal cases (3.2%) and 3.9% lost to follow-up. The mortality was significantly increased when comparing index HCV⁺ siblings with either index HCV^­ siblings, MRR = 2.89 (95%CI 2.00 to 4.19), or control siblings, MRR = 3.34 (95%CI 2.51 to 4.39), but not when comparing index HCV^­ siblings with control siblings, MRR = 1.15 (95%CI 0.91 to 1.45). In analyses restricted to siblings born in Denmark, born after 1967, one sibling per family, or with observation time restricted to the period after the index patient was diagnosed with HIV, the mortality estimates were essentially unchanged.

Conclusions:  HCV/HIV-co-infected patients experienced more sibling mortality than both HIV-mono-infected patients and controls. This implies that factors other than pathogenicity of the HCV contribute to the increased mortality in co-infected patients. The disparity in relative mortality of HCV-co-infected patients in different studies may be explained by different clinical settings with different socioeconomic risk factors associated with specific transmission groups. It is crucial to ascertain causes of death in HCV prognosis and mortality studies.