Preventing Deaths in Persons With HIV/Hepatitis B Virus Coinfection: A Call to Accelerate Prevention and Treatment Efforts

Abstract

The prognosis associated with a new diagnosis of human immunodeficiency virus (HIV) infection has improved dramatically since the virus was first recognized [1]. However, the remarkable increases in survival have been attenuated in some groups because of the presence of comorbid infectious diseases and other illnesses. Globally, an estimated 5%–10% of the 33.3 million people living with HIV are coinfected with the hepatitis B virus (HBV). This double-whammy of HIV/HBV coinfection has translated into poorer outcomes. For instance, in settings where expanded access to antiretroviral therapy (ART) has reduced deaths from HIV, liver-related death (from any of a variety of etiologies) has emerged as an important cause for the remaining mortality [2]. Infection with HIV increases the rate of replication of HBV, thereby accelerating progression to cirrhosis, hepatocellular carcinoma, and other liver-related morbidity [3]. There is not clear evidence that HBV impacts the progression of HIV disease, but it has been speculated that HBV infection increases susceptibility to liver toxicity from ART and impairs the immunological response (eg, CD4 cell–count recovery) to HIV treatment. Evaluating whether HIV progression is an important element of the increased mortality seen in coinfected patients has been challenging because of the heterogeneity of available HIV and HBV data in studies reported to date. The report by Chun et al [4] in this issue of The Journal presents data from the U.S. Military HIV Natural History Study, which evaluates the impact of HBV coinfection on the composite endpoint of AIDS-defining illness or death. To minimize the influence of duration of HIV infection, the analysis was limited to the 2352 cohort participants whose date of HIV seroconversion could be estimated within 3 years, and whose HBV status was known or determined within 2 years of HIV seroconversion (although the timing of their HBV infection was not known). Each patient’s HBV status was classified as either chronic (hepatitis B surface antigen [HBsAg] reactivity), resolved (hepatitis B core antibody [HBcAb] and surface antibody [HBsAb] reactivity with a negative HBsAg), isolated HBcAb (HBcAb reactivity with negative HBsAb and HBsAg), or no evidence of past or current infection (negative HBcAb and HBsAg). Patients classified as having chronic HBV were observed to have a higher risk (approximately double the risk in adjusted analysis) for developing the composite outcome of AIDS-defining illness or death, compared with that of patients who were HBV negative. Hepatitis C virus (HCV) infection was uncommon in this cohort (1.7% of patients had a reactive HCV antibody test), but was also associated with an increased risk of developing an AIDS-defining illness or death. Some strengths of this analysis were the focus on individuals with known dates of HIV seroconversion to minimize survivorship bias, and the classification of HBV status around the HIV seroconversion date to minimize misclassification bias. Although the findings suggest that HBV infection may impact HIV outcomes, as with any cohort study there are methodological limitations that restrict our ability to determine causality. A limitation is that HBV infection directly causes mortality, and these deaths would be counted toward the composite outcome. In both HIV-infected and -uninfected populations, HBV infection is associated with a higher risk of mortality Received 26 September 2011; accepted 26 September 2011; electronically published 5 December 2011. Correspondence: Barbara Marston, Centers for Disease Control and Prevention, 1600 Clifton Rd, Mailstop A-05, Atlanta, GA 30329 (bxm5@cdc.gov). The Journal of Infectious Diseases 2012;205:166–8 Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2011. DOI: 10.1093/infdis/jir728