Prevention and Management of Hepatitis A Virus in Adults With HIV

Purpose and Development of This Guideline

Reviewed and updated: Hector I. Ojeda-Martinez, MD; May 2021
Writing group: Joseph P. McGowan, MD, FACP, FIDSA; Steven M. Fine, MD, PhD; Rona Vail, MD; Samuel T. Merrick, MD; Asa Radix, MD, MPH, PhD; Christopher J. Hoffmann, MD, MPH; Charles J. Gonzalez, MD
Committee: Medical Care Criteria Committee
Date of original publication: August 2018

This guideline on hepatitis A virus (HAV) and HIV coinfection was developed by the New York State (NYS) Department of Health (DOH) AIDS Institute (AI). The purpose of this guideline is to inform NYS clinicians about HAV/HIV coinfection, including screening, vaccination, and post-exposure prophylaxis, to accomplish the following:

• Increase the number of individuals in NYS with HIV who are screened and vaccinated against HAV.
• Provide evidence-based recommendations for post-exposure prophylaxis in adults with HIV who experience an HAV exposure.
• Integrate current evidence-based clinical recommendations into the healthcare-related implementation strategies of the Ending the Epidemic initiative, which seeks to end the AIDS epidemic in NYS.

The NYSDOH AI guideline Comprehensive Primary Care for Adults With HIV includes recommendations for HAV vaccination.

Burden of HAV

The total annual reported cases of HAV in the United States decreased consistently between 2000 (13,397 cases) and 2014 (1,239 cases), with the decline attributed to the inclusion of HAV vaccination in the recommended pediatric immunization panels for children aged 2 to 18 years [CDC 2018]. Since 2014, however, the number of cases reported in the United States has increased, reaching 12,474 in 2018 [CDC 2020]. In 2017 and 2018, outbreaks among people who use drugs, homeless people, and men who have sex with men (MSM) contributed to substantial increases in the reported cases of HAV. A study using nationally representative data found that from 2007 to 2016, HAV susceptibility among nonvaccinated U.S.-born adults aged 20 years or older was approximately 74.1% [Yin, et al. 2020].

In 2019, the NYSDOH issued an advisory on increases in HAV infection and noted the following:

• In NYS (excluding New York City) the annual number of reported HAV cases (2,019) represented a 235% increase between 2016 and 2018 [NYSDOH 2019].
• People at high risk for HAV infection are those who use injection or noninjection drugs, have unstable housing or are homeless, are or were recently incarcerated, and who are MSM [NYSDOH 2019].
• In New York City, the number of reported HAV cases increased 64% from 2018 to 2019, with the increase largely due to outbreaks among MSM [NYCDOHMH 2020].

Development of This Guideline

This guideline was developed by the NYSDOH AI Clinical Guidelines Program, which is a collaborative effort between the NYSDOH AI Office of the Medical Director and the Johns Hopkins University School of Medicine, Division of Infectious Diseases.

Established in 1986, the goal of the Clinical Guidelines Program is to develop and disseminate evidence-based, state-of-the-art clinical practice guidelines to improve the quality of care provided to people who have HIV, hepatitis C virus (HCV), or sexually transmitted infections; people with substance use issues; and members of the LGBTQ community. NYSDOH AI guidelines are developed by committees of clinical experts through a consensus-driven process.

The NYSDOH AI charged the Medical Care Criteria Committee (MCCC) with developing evidence-based clinical recommendations to guide primary care and other medical care providers in HAV vaccination and post-exposure prophylaxis in patients with HIV, and in the management of HIV/HCV coinfection. The resulting recommendations are based on extensive review of the medical literature and reflect consensus among the committee members. Each recommendation is rated for strength and quality of the evidence based on the rating scheme below. If a recommendation is based on expert opinion, the rationale for the opinion is provided in the text.

References

CDC. Surveillance for Viral Hepatitis – United States, 2016. 2018 Apr 16. https://www.cdc.gov/hepatitis/statistics/2016surveillance/index.htm [accessed 2021 Mar 19]

CDC. Hepatitis A Outbreaks in the United States. 2020 Jul 28. https://www.cdc.gov/hepatitis/outbreaks/hepatitisaoutbreaks.htm [accessed 2021 Mar 19]

NYCDOHMH. New York City Department of Health and Mental Hygiene: Hepatitis A, B, and C in New York City: 2019 Annual Report. 2020 Dec. https://hepfree.nyc/wp-content/uploads/2020/12/Viral-Hep-2019-Annual-Report_Final_Web.pdf [accessed 2021 Mar 24]

NYSDOH. New York State Department of Health. Health Advisory: Outbreak of Hepatitis A Virus. 2019 Dec 12. https://www.health.ny.gov/diseases/communicable/hepatitis/hepatitis_a/docs/2019-12-12_health_advisory.pdf [accessed 2021 Mar 22]

Transmission and Prevention

Reviewed and updated: Hector I. Ojeda-Martinez, MD, with the Medical Care Criteria Committee; May 2021

Transmission

The modes of HAV transmission are well established: ingestion of contaminated water and food, such as raw clams or oysters; oral-anal contact; person-to-person spread via fomites, such as shared utensils or bath towels; or, very rarely, blood or blood product transfusion. In the last few years, HAV outbreaks have largely been attributed to foodborne transmission and close person-to-person contact with an individual with HAV [CDC 2020].

Men who have sex with men (MSM) and individuals who use drugs are at increased risk for HAV infection, and data from the National Health and Nutrition Examination Survey 2007 to 2016 indicate that, among adults born in the United States aged ≥20 years, the prevalences of HAV susceptibility and nonvaccination, respectively, were 67.5% and 65.2% among MSM and 72.9% and 73.1% among individuals who reported injection drug use [Yin, et al. 2020].

Pre-Exposure Vaccination

All adults with HIV should receive an HAV IgG test, and those who are antibody-negative should be vaccinated against HAV [Nelson, et al. 2020].

Infection with HAV can be prevented by active immunization before exposure with either of the 2 currently licensed vaccines, which are considered equivalent in efficacy. HAV vaccines are highly immunogenic in immunocompetent adults, with >95% seroconversion. However, the seroconversion rates and the geometric mean serum antibodies in individuals with HIV are lower than in those without HIV, with response rates from 50% to 95% [Kemper, et al. 2003; Wallace, et al. 2004; Rimland and Guest 2005; Shire, et al. 2006; Weissman, et al. 2006; Mena, et al. 2013]. HAV vaccine appears to have no effect on the course of HIV infection or on plasma HIV viral load. A combined HAV and hepatitis B virus vaccine is also available and can be used in people susceptible to both hepatitis A and B. It is given in three total doses at 0, 1, and 6 months.

Administration of HAV vaccine is recommended for all adults with HAV regardless of CD4 count. An effective antibody response may not occur in up to 15% of immunocompromised patients [Wallace, et al. 2004; Mena, et al. 2013]. This Committee recommends follow-up HAV antibody testing for patients who are at increased risk for HAV-related morbidity and mortality (see above) to verify vaccine efficacy and to identify those who should be counseled to avoid infection because of continued susceptibility.

Post-Exposure Immune Globulin

Immune serum globulin is the recommended HAV post-exposure prophylaxis for patients with HIV and should be given to individuals who are susceptible to HAV infection within 2 weeks after an exposure to an HAV-infected household contact, sexual partner, or needle-sharing partner [ACIP 2007; CDC 2020]. Consideration should also be given to patients with HIV who are providing other types of ongoing, close personal contact with someone with HAV (e.g., a regular babysitter or caretaker) [ACIP 2007; CDC 2020]. A single dose of 0.1 mL/kg intramuscularly is effective in preventing infection or attenuating HAV infection that might result from such an exposure [Nelson 2017]. Concurrent administration of HAV vaccine with immune serum globulin is indicated for individuals at risk for future infection (see above).

References

ACIP. Update: Prevention of hepatitis A after exposure to hepatitis A virus and in international travelers. Updated recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 2007;56(41):1080-1084. [PMID: 17947967]

CDC. Hepatitis A Outbreaks in the United States. 2020 Jul 28. https://www.cdc.gov/hepatitis/outbreaks/hepatitisaoutbreaks.htm [accessed 2021 Mar 19]

Kemper CA, Haubrich R, Frank I, et al. Safety and immunogenicity of hepatitis A vaccine in human immunodeficiency virus-infected patients: a double-blind, randomized, placebo-controlled trial. J Infect Dis 2003;187(8):1327-1331. [PMID: 12696015]

Mena G, García-Basteiro AL, Llupià A, et al. Factors associated with the immune response to hepatitis A vaccination in HIV-infected patients in the era of highly active antiretroviral therapy. Vaccine 2013;31(36):3668-3674. [PMID: 23777950] 

Nelson NP. Updated dosing instructions for immune globulin (human) GamaSTAN S/D for hepatitis A virus prophylaxis. MMWR Morb Mortal Wkly Rep 2017;66(36):959-960. [PMID: 28910270] 

Nelson NP, Weng MK, Hofmeister MG, et al. Prevention of hepatitis A virus infection in the United States: Recommendations of the Advisory Committee on Immunization Practices, 2020. MMWR Recomm Rep 2020;69(5):1-38. [PMID: 32614811] 

Rimland D, Guest JL. Response to hepatitis A vaccine in HIV patients in the HAART era. AIDS 2005;19(15):1702-1704. [PMID: 16184045] 

Shire NJ, Welge JA, Sherman KE. Efficacy of inactivated hepatitis A vaccine in HIV-infected patients: a hierarchical bayesian meta-analysis. Vaccine 2006;24(3):272-279. [PMID: 16139398] 

Wallace MR, Brandt CJ, Earhart KC, et al. Safety and immunogenicity of an inactivated hepatitis A vaccine among HIV-infected subjects. Clin Infect Dis 2004;39(8):1207-1213. [PMID: 15486846] 

Weissman S, Feucht C, Moore BA. Response to hepatitis A vaccine in HIV-positive patients. J Viral Hepat 2006;13(2):81-86. [PMID: 16436125] 

Yin S, Barker L, Ly KN, et al. Susceptibility to hepatitis A virus infection in the United States, 2007-2016. Clin Infect Dis 2020;71(10):e571-e579. [PMID: 32193542]

Management of HAV/HIV Coinfection

Reviewed and updated: Hector I. Ojeda-Martinez, MD, with the Medical Care Criteria Committee; May 2021

Morbidity and mortality: The incubation period of HAV infection averages 28 days (range, 15 to 50 days). Although HAV does not cause chronic hepatitis, it is not a benign disease; the morbidity in adults is substantial. Young children tend to have asymptomatic or minimally symptomatic disease, whereas older children and adults have more severe illness, with jaundice occurring in approximately 70% of cases [Cuthbert 2001]. Adults with acute HAV lose an average of 30 workdays [WHO 2000], and approximately 40.8% of patients with reported cases of acute HAV required hospitalization in 2013 [CDC 2015]. Overall case fatality is low, ranging from 0.3% to 0.6% for all ages and up to 1.8% among adults aged >50 years [CDC 2015].

Coinfection: HAV does not cause more severe clinical illness in people with HIV than in people without. Patients with HIV may have significantly higher HAV viral load levels and significantly prolonged durations of HAV viremia than people who do not have HIV [Gallego, et al. 2011], which may result in a prolonged duration of risk of HAV transmission to others.

Maintain ART: Patients with HIV and acute HAV infection rarely require even temporary interruption of ART. Cessation of ART should be avoided whenever possible because of the potential long-term consequences, such as reduced viral suppression when ART is reinstituted [Lutwick 1999; El-Sadr, et al. 2008]. In the rare instances when interruption of ART is indicated for management of fulminant liver disease, clinicians should consult with a care provider experienced in the treatment of hepatitis and HIV.

References

CDC. Surveillance for Viral Hepatitis – United States, 2013. 2015 May 31. https://www.cdc.gov/hepatitis/statistics/2013surveillance/index.htm [accessed 2021 Mar 19]

Cuthbert JA. Hepatitis A: old and new. Clin Microbiol Rev 2001;14(1):38-58. [PMID: 11148002] 

El-Sadr WM, Grund B, Neuhaus J, et al. Risk for opportunistic disease and death after reinitiating continuous antiretroviral therapy in patients with HIV previously receiving episodic therapy: a randomized trial. Ann Intern Med 2008;149(5):289-299. [PMID: 18765698] 

Gallego M, Robles M, Palacios R, et al. Impact of acute hepatitis A virus (HAV) infection on HIV viral load in HIV-infected patients and influence of HIV infection on acute HAV infection. J Int Assoc Physicians AIDS Care (Chic) 2011;10(1):40-42. [PMID: 21368013] 

Lutwick LI. Clinical interactions between human immunodeficiency virus and the human hepatitis viruses. Infect Dis Clin Pract 1999;8(1):9-20. https://journals.lww.com/infectdis/Citation/1999/01000/CLINICAL_INTERACTIONS_BETWEEN_HUMAN.3.aspx

WHO. Hepatitis A. 2000 Jul. https://www.who.int/csr/resources/publications/hepatitis/WHO_CDS_CSR_EDC_2000_7/en/ [accessed 2021 Mar 19]

All Recommendations

Reviewed and updated: Hector I. Ojeda-Martinez, MD, with the Medical Care Criteria Committee; May 2021

How This Guideline Was Developed

This guideline was developed by the New York State (NYS) Department of Health (DOH) AIDS Institute (AI) Clinical Guidelines Program, which is a collaborative effort between the NYSDOH AI Office of the Medical Director and the Johns Hopkins University School of Medicine, Division of Infectious Diseases.

Established in 1986, the goal of the Clinical Guidelines Program is to develop and disseminate evidence-based, state-of-the-art clinical practice guidelines to improve the quality of care provided to people with HIV, hepatitis C virus, or sexually transmitted infections; people with substance use issues; and members of the LGBTQ community. NYSDOH AI guidelines are developed by committees of clinical experts through a consensus-driven process.

Medical Care Criteria Committee (MCCC) for adult HIV care guidelines: The NYSDOH AI charged the MCCC (adult HIV and related guidelines) with developing evidence-based recommendations for clinicians in NYS who provide care to individuals with HIV. The purpose of the Prevention and Management of Hepatitis A Virus in Adults With HIV clinical practice guideline is to inform NYS clinicians about hepatitis A virus (HAV)/HIV coinfection, including screening, vaccination, and post-exposure prophylaxis.

Committee makeup: Members of the MCCC (see Box A1: MCCC Leaders and Members, below) were appointed by the NYSDOH AI to ensure representation of clinical practice in all major regions of the state, relevant medical disciplines and subspecialties, key NYS agencies, community stakeholders, and patient advocates. Individuals confirmed as MCCC members are required to disclose any potential conflicts of interest; disclosures are reviewed and approved by the NYSDOH AI Office of the Medical Director (see Funding and Disclosure of Potential Conflicts of Interest, below).

Committee role: Committee members actively participate in guideline development, including evidence review, drafting of recommendations and text, manuscript review, consensus approval of all recommendations, and rating of recommendations.

Committee leadership: Working with the lead author, the MCCC Writing Group reviewed and refined the manuscript, facilitated consensus approval of all recommendations, and addressed feedback from the Committee at large.

Johns Hopkins University (JHU) Editorial Role: The JHU editorial team coordinated, guided, and documented all Committee activities and edited the guideline material for clarity, flow, and style.

MCCC Writing Group (all Committee members and reviewers are listed in Box A1, below)

• Joseph P. McGowan, MD, FACP, FIDSA, Chair
• Steven Fine, MD, PhD, Co-Vice-Chair (effective January 2021)
• Rona Vail, MD, Co-Vice-Chair (effective January 2021)
• Samuel T. Merrick, MD, Chair Emeritus
• Charles J. Gonzalez, MD, AI Medical Director
• Asa Radix, MD, MPH, FACP, AAHIVS
• Christopher J. Hoffmann, MD, MPH, Director, JHU-NYSDOH Guidelines Program

AIDS Institute and JHU Editorial and Program Management Team

• Laura Duggan Russell, MPH, AI Guidelines Program Manager
• Mary Beth Hansen, MA, JHU Guidelines Project Director
• Johanna Gribble, MA, JHU Medical Editor
• Jen Ham, MPH, JHU Medical Editor
• Rachel Lastra, JHU Medical Editor
• Jesse Ciekot, JHU Program Coordinator

Funding and disclosure of potential conflicts of interest (COIs): NYS funds supported the development of this guideline through a grant awarded to the JHU School of Medicine, Division of Infectious Diseases, from the NYSDOH AI.

All active MCCC members, invited consultants and coauthors, peer reviewers, and program staff are required to disclose financial relationships with commercial entities, including gifts that may be actual conflicts of interest or may be perceived as conflicts. These individuals must disclose financial relationships annually, for themselves, their partners/spouses, and their organization/institution. On their annual disclosures, MCCC members are asked to report for the previous 12 months and the upcoming 12 months. 

All reported financial relationships with commercial entities are reviewed by the NYSDOH AI guidelines program to assess the potential for undue influence on guideline recommendations made by the Committee.

All guideline recommendations received consensus approval of the full MCCC, and the final review and approval of the recommendations were performed by the Committee Chair and the NYSDOH AI Medical Director and Deputy Medical Director, none of whom reported conflicts of interest.

Evidence collection and review: The NYSDOH AI guideline development process is based on a strategic search and analysis of the published evidence. Box A2 illustrates the evidence review and selection process.

Recommendation development and rating process: When this guideline was originally developed, the standard development process was followed. Clinical recommendations were developed by consensus based on a synthesis of the current evidence collected through the systematic search described above. If no data were available, the recommendations are based on expert opinion, and this status is indicated in the rating and the text. Once consensus among the Writing Group members was reached, the guideline was reviewed by the full MCCC, and consensus was reached on all recommendations. Writing Group review discussions were recorded, and recordings were reviewed carefully to ensure that all decisions and changes were captured and integrated into the manuscript. Members of the Writing Group then individually reviewed the evidence for each recommendation and assigned a 2-part rating (see below). The individual ratings were compiled into a report distributed to all raters, and conference call discussions were held to deliberate ratings for which consensus was needed. Once all raters agreed on the interpretation of evidence and ratings for all recommendations, the guideline was sent to the NYSDOH AI for review and approval.

The current guideline reflects a review and update that was completed at the 3-year anniversary of publication. New literature was reviewed by a member of the MCCC and minor updates were made, which were then reviewed and approved by the Writing Group.

Guideline updates: Members of the MCCC will monitor developments in an ongoing structured manner to maintain guideline currency. Once the guidelines are published on the program website: www.hivguidelines.org, any updates will be made to the HTML document as needed as new, peer-reviewed literature is published if evidence is made available that changes best practices.

Notification of newly published studies will be automated, and the Writing Group will review new data as available. Newly published data that provide support for existing recommendations will be cited in the text, and the studies will be added to the reference list(s).

If newly published data prompt a revision to recommendations or rationale, the lead author and the Writing Group will propose appropriate edits and determine whether the changes warrant review and approval by the entire MCCC. If MCCC review is required, JHU will distribute updates via email, and a conference call will be convened if required. Deletion of existing recommendations, addition of any new recommendations, or substantive changes to existing recommendations will prompt MCCC review and consensus.

The full guideline will be reviewed and updated on the fourth anniversary of original publication to prepare for publication of an updated guideline on or before the fifth anniversary of original publication.

Updates to This Guideline

May 2021

• Recommendation updated in Transmission and Prevention section: Clinicians should obtain a hepatitis A virus (HAV) immunoglobulin G (IgG) antibody measurement for all individuals with HIV [a] and should administer the HAV vaccine to those who are HAV antibody-negative, regardless of CD4 count.
• Citations and references have been updated throughout the guideline.
• New epidemiologic data added to Burden of HAV section: A study using nationally representative data found that from 2007 to 2016, HAV susceptibility among nonvaccinated U.S.-born adults aged 20 years or older was approximately 74.1% [Yin, et al. 2020].

August 2018

• Two new sections added:
  • Purpose of This Guideline, including: The Burden of HAV, The Role of the NYS Primary Care Provider, and Development of this Guideline
  • Transmission and HAV Disease, including: Severity of Disease and Disease Management in the Setting of HIV
• Updated recommendation in Prevention: The dosing for post-exposure immune globulin was updated to 0.1 mL/kg IM, based on updated CDC recommendation: Nelson N. Updated Dosing Instructions for Immune Globulin (Human) GamaSTAN S/D for Hepatitis A Virus Prophylaxis. MMWR Morb Mortal Wkly Rep 2017; 66:959-960. https://www.cdc.gov/mmwr/volumes/66/wr/mm6636a5.htm [accessed 2018 Aug 24].