HBV-HIV Coinfection Research Network
Condition: Hepatitis B; Human Immunodeficiency Virus
MeSH terms: Hepatitis B; Acquired Immunodeficiency Syndrome; HIV Infections; Coinfection
Study type: Observational

Summary: 
      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.
    

Detailed description: 
      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.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        HBV-HIV coinfection
      
Biospecimen description: 
      Serum at baseline and every 6 months for 4 years. Liver biopsy at baseline and year 4
    
Keywords: HIV; HBV