HBV-HIV Coinfection Research Network
HBV-HIV Coinfection Research Network
Despite effective ART that can suppress both HIV and HBV, HBV-related liver disease remains a
 significant co-morbidity in this population. Little is known about the histologic spectrum of
 liver disease, the significance of complete vs. incomplete HBV suppression, the utility of
 novel virologic and serum markers of disease severity, and the long-term renal and bone
 effects of TDF-based therapy. This proposal will address these important questions and impact
 the science and health of those coinfected with HBV-HIV.
Since the introduction of highly active antiretroviral therapy (ART) in 1996, there has been
 a dramatic reduction in morbidity and mortality among those living with HIV. However, chronic
 liver disease due to coinfection with hepatitis B (HBV) or C (HCV) virus has emerged as the
 second leading cause of mortality among HIV-infected persons. The natural history of HBV
 infection is altered in those with HIV. Current guidelines recommend that most coinfected
 patients be treated for both HIV and HBV infection using combinations of ART that include
 tenofovir (TDF). Despite widespread adoption in the US, the effect of this regimen on
 long-term outcomes of HBV disease such as histologic severity, progression, and risk of
 emergence of resistant HBV variants, and the long term risks of TDF therapy remains
 unanswered. Further investigation is required to address the following important questions:
 (1) what is the proportion of HIV-coinfected patients who have incomplete viral suppression
 on TDF?; (2) is incomplete suppression of HBV acceptable in HIV coinfected persons and if so,
 what threshold HBV DNA level constitutes an adequate clinical goal?; (3) in view of the lack
 of acceptance of liver biopsy among HIV practitioners, can noninvasive markers accurately
 assess HBV disease activity and the impact of ART on disease progression?; (4) What are the
 long term risks of TDF-based therapy for HBV in HIV coinfection? In short, what are the risks
 and benefits of TDF-based therapy for CHB in patients with HIV coinfection? The NIH Hepatitis
 B Research Network (HBRN) is the first major effort to elucidate the natural history and
 treatment outcomes of persons with chronic HBV the US. The HBRN will not address the critical
 issue of HBV liver disease progression in HIV-infected persons because patients with HIV
 coinfection will be excluded. The current proposal, an approved ancillary study of the HBRN,
 offers a unique opportunity to fill major gaps in HBV-HIV knowledge and to compare HBV-HIV
 infected persons to those with HBV monoinfection participating in the HBRN. No other funded
 research network in North America has the expertise, patient population, and structure to
 carry out the proposed studies. The Specific Aims are: 1. Define the problem. We will
 clinically, histologically, serologically, and virologically characterize a well-defined
 cohort of HBV-HIV patients in North America in a cross-sectional manner; 2. Define the
 benefit of long term therapy. We will longitudinally determine the impact of complete vs.
 incomplete viral suppression on clinical and serologic outcomes, and histologic progression
 by paired biopsy and 2a. Define a threshold HBV DNA level associated with disease
 progression; 2b. Establish the utility of noninvasive assessment of hepatic fibrosis compared
 with biopsy; and 2c. Define the frequency of genotypic and phenotypic TDF resistance with
 long term therapy; and finally 3. Define the risk of long term therapy. We will assess the
 long term renal and bone effects of TDF-based therapy in the HBV-HIV cohort. Collectively,
 this study will fulfill many of the key priorities outlined in the NIH Action Plan for Liver
 Disease for HBV-HIV coinfection.
Inclusion Criteria: (1) Male and female subjects ≥ 18 years of age; (2) Serologic evidence
 of HIV infection by HIV antibody positivity or positive HIV-RNA > 6 months prior to
 screening (3) Serologic evidence of chronic hepatitis B infection by HBsAg positivity(4)
 Willingness to provide informed consent.

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 Exclusion Criteria: (1) Estimated life expectancy of less than one year based on clinical
 judgment of the investigator; (2) Hepatic decompensation as defined by presence of ascites
 or hepatic hydrothorax, variceal or portal hypertensive bleeding, hepatic encephalopathy,
 or Child-Turcotte-Pugh (CTP) score of 7 or above; (3) Hepatocellular carcinoma (HCC); (4)
 Anti-HCV positive; (5) History of solid organ or bone marrow transplantation; (6) Pregnant
 women; (7) Medical or social condition which in the opinion of the study physician would
 make the patient unsuitable for the study or will interfere with or prevent follow-up per
 protocol; (8) Unable or unwilling to return for follow-up visits; (9) Contraindications to
 liver biopsy.

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