Triple trouble: infection with hepatitis B increases risk of death for people with HIV and hepatitis C co-infection

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Infection with hepatitis B virus (HBV) is associated with a poorer prognosis for people living with HIV who are co-infected with hepatitis C virus (HCV), Spanish investigators report in a study published in the online edition of AIDS. After taking into account other factors, people with HIV and hepatitis C co-infection who were also infected with hepatitis B had a 75% increase in their mortality risk compared to individuals who were only infected with HIV and hepatitis C.

“Our results provide the strongest evidence to date that HBV infection significantly worsens the prognosis of HIV/HCV co-infected patients,” write the authors.

HIV, hepatitis B and hepatitis C share similar modes of transmission. A considerable amount is known about co-infection with HIV and hepatitis C, as well as about co-infection with HIV and hepatitis B. However, the consequences of infection with all three viruses are poorly understood.


hepatitis B virus (HBV)

The hepatitis B virus can be spread through sexual contact, sharing of contaminated needles and syringes, needlestick injuries and during childbirth. Hepatitis B infection may be either short-lived and rapidly cleared in less than six months by the immune system (acute infection) or lifelong (chronic). The infection can lead to serious illnesses such as cirrhosis and liver cancer. A vaccine is available to prevent the infection.

person years

In a study “100 person years of follow-up” could mean that information was collected on 100 people for one year, or on 50 people for two years each, or on ten people over ten years. In practice, each person’s duration of follow-up is likely to be different.


The prospect of survival and/or recovery from a disease as anticipated from the usual course of that disease or indicated by the characteristics of the patient.

AIDS defining condition

Any HIV-related illness included in the list of diagnostic criteria for AIDS, which in the presence of HIV infection result in an AIDS diagnosis. They include opportunistic infections and cancers that are life-threatening in a person with HIV.

end-stage disease

Final period or phase in the course of a disease leading to a person's death.

Investigators from the Spanish VACH cohort therefore designed a study involving 6342 people who were co-infected with HIV and hepatitis C. The primary aim of the study was to see if chronic hepatitis B virus infection (hepatitis B surface antigen [HBsAg] positive) was associated with increased mortality risk.

The prevalence of hepatitis B virus infection was 6%. People infected with all three viruses were slightly older (37 vs 36 years, p < 0.01), more likely to be male (87 vs 80%, p = 0.001), had a lower CD4 cell count (251 vs 293 cells/mm3, p = 0.006) and had a higher APRI score (AST to platelet index; 1.10 vs 0.82, p = 0.002) than people who were only infected with HIV and hepatitis C.

Overall, the study participants contributed almost 26,000 person-years of follow-up. There were a total of 543 deaths, providing a mortality rate of 2.1 deaths per 100 person years.

However, mortality rates differed according to hepatitis B virus infection status, and were 3.78 per 100 person-years for those infected with hepatitis B, and 2.01 per 100 person-years for people who were hepatitis B virus-negative.

Initial analysis therefore showed that infection with hepatitis B increased mortality risk for people with HIV/hepatitis C co-infection by 90% (1.90; 95% CI, 1.42-2.54).

Several other factors, including a prior AIDS-defining illness, age, HIV and hepatitis C treatment histories, CD4 cell count and viral load also affected mortality risk.

The investigators therefore performed a second set of analysis which took these factors into account.

This showed that hepatitis B virus infection increased mortality risk by approximately 75% (1.745; 95% CI, 1.41-2.67). Other factors associated with a worse outcome included older age and a detectable HIV viral load. A higher CD4 cell count, HIV therapy, treatment with tenofovir (Viread, also in Truvada, Atripla and Eviplera), which is active against both HIV and hepatitis B, and hepatitis C therapy were all associated with a reduction in mortality risk.

The investigators highlighted the findings of earlier research involving the same patient cohort that showed that hepatitis B virus infection was the most important factor affecting the risk of end-stage liver disease in people with HIV/hepatitis C co-infection. The results of the present research showed that liver-related deaths were more common in those infected with all three viruses than in people with HIV/hepatitis C co-infection (42 vs 24%).

Findings of this study underline the importance of hepatitis B vaccination for everyone with or at risk of infection with HIV.


Teira R et al. Hepatitis B virus infection predicts mortality of HIV and hepatitis C virus co-infected patients. AIDS 27, online edition. DOI: 10.1097/QAD.0b013e32835ecaf7, 2013.