Predictors of HBV infection in HIV infected individuals

Predictors of Chronic HBV Infection in HIV-infected Individuals
Reported by Jules Levin
CROi 2009 Montreal Feb 8-12
Michael Landrum*1,2, A Fieberg2,3, H Chun4, A Ganesan2,5, N Crum-Cianflone2,6, V Marconi1, G Wortmann7, R Barthel8, and S Wegner2
1San Antonio Military Med Ctr, TX, US; 2Infectious Disease Clinical Res Prgm, Uniformed Svcs Univ of the Hlth Sci, Bethesda, MD, US; 3Univ of Minnesota, Minneapolis, US; 4Naval Hlth Res Ctr, San Diego, CA, US; 5Natl Naval Med Ctr, Bethesda, MD, US; 6Naval Med Ctr, San Diego, CA, US; 7Walter Reed Army Med Ctr, Washington, DC, US; and 8Naval Med Ctr, Portsmouth, VA, US
AUTHOR CONCLUSIONS: Several identified risk factors suggest immune function is an important determinant of HBV outcome, specifically the development of chronic HBV infection. Chronic compared to non-chronic HBV infection was associated with:
•Infection with HBV after HIV infection
•Lower CD4 cell count at the time of HBV diagnosis
•Lack of HAART use prior to HBV diagnosis
• Benefit from HAART was seen even for those with CD4 ≥350 cells/mL. In those initially with non-chronic HBV who later developed chronic HBV, CD4 cell counts were significantly lower at the onset of chronic disease. These data suggest immunologic dysfunction may be an important determinant of HBV outcome, and imply HAART in addition to anti-HBV agents may improve HBV outcomes following therapy, supporting current HIV treatment guidelines.
Background: Factors associated with chronic compared to resolved hepatitis B virus (HBV) infection in HIV-infected individuals remain poorly understood, yet such knowledge may lead to improvements in the treatment of chronic HBV infection. Therefore, we evaluated factors associated with chronic HBV infection among participants with HBV infection in the Tri-service AIDS Clinical Consortium (TACC) HIV Natural History Study.
Methods: Eligible participants had a documented positive HIV test and were HBV infected. HBV infection was defined as the presence of hepatitis B core antibody (HBcAb) concurrently with hepatitis B surface antigen (HBsAg) or HBsAb, or the presence of HBsAg or HBcAb on at least 2 occasions. Chronic HBV was defined as the presence of HBsAg on ≥2 occasions at least 6 months apart. HBV infection after HIV diagnosis was defined as infection occurring in participants serologically negative for HBV at the time of HIV seropositivity. Risk factors for chronic HBV infection were determined using logistic regression for all eligible participants and for the subset with HBV infection after HIV diagnosis. Odds ratios (OR) are given with 95% confidence intervals (CI).
Results: Of 2131 participants with a diagnosis of HBV infection enrolled from 1986 to 2008, 281 (13%) had chronic HBV. Overall, after adjusting for age and ethnicity, risk of chronic HBV was increased for those with HBV infection occurring after HIV diagnosis (OR 1.88, 95%CI 1.36 to 2..60) and reduced for those with higher CD4 count at the time HBV diagnosis (OR 0.90, 95%CI 0.85 to 0.94 per 100 cells/µL increase). Of the 282 with known HBV infection after HIV diagnosis, 60 (21%) were chronic. In multivariate analysis of HBV infections after HIV, use of HAART was associated with reduced risk of chronic infection (OR 0.21, 95%CI 0.05 to 0.93). Even in those with CD4 ≥350 cells/µL, HAART use was associated with lower risk of chronic infection (0 of 24 for those on HAART at the time of HBV diagnosis compared to 26 of 131(20%) for those not on HAART, p = 0.01).
Conclusions: Immunologic dysfunction may be an important determinant regarding HBV outcome, as higher CD4 cell count and HAART use at the time of HBV diagnosis were associated with reduced risk of chronicity. These data suggest that HAART use may improve HBV disease control in co-infected patients, indirectly supporting current guidelines recommending initiation of HAART for those needing HBV treatment.
INTRODUCTION
HBV infection is a leading cause of morbidity and mortality among HIV-infected patients.1-3Factors at the time of HBV infection associated with development of chronic disease, including CD4 count and HAART use, are not well characterized.
• Increased understanding of these factors may lead to better HBV outcomes through improved treatment strategies.The relative impact upon HBV outcomes of therapy targeting immune dysfunction or HBV directly is not well described.
•Immune restoration following HAART has been postulated to improve the course of chronic HBV infection.4
•Recently updated HIV treatment guidelines encouraged initiation of HAART in addition to HBV treatment for patients with active co-infection, but data supporting this practice are limited.5Therefore, we sought to describe the association between clinical factors at the time of HBV infection and risk of chronic HBV disease in our observational cohort.
METHODS
Study Design
•The U.S. Military HIV Natural History Study Cohort
•Observational cohort at 7 military medical treatment facilities in the U.S.
•Enrolling since 1986; more than 5000 participants with signed, written consent
•Eligibility for analysis
•Serologically documented HBV/HIV co-infection
•Chronic HBV defined as positive HBsAgon two occasions at least 6 months apart
•Participants categorized by timing of HBV infection relative to HIV (at/after/unknown) and grouped by chronic HBV status for analysisStatistical Methods
•Comparison of group baseline characteristics using general linear models and chi-squared tests
•Risk for chronic HBV assessed by univariateand multivariate logistic regression
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