Purpose of This Guideline
Reviewed and updated: Hector I. Ojeda-Martinez, MD; May 21, 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 Department of Health AIDS Institute (NYSDOH AI). The purpose of this guideline is to inform New York State clinicians about HAV/HIV coinfection, including screening, vaccination, and post-exposure prophylaxis, to accomplish the following:
- Increase the number of individuals in New York State 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 New York State.
The NYSDOH AI guideline Immunizations 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 New York State (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].
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 21, 2021
RECOMMENDATIONS |
Pre-Exposure Vaccination
Post-Exposure Immune Globulin
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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 21, 2021
RECOMMENDATION |
Management of HAV/HIV Coinfection
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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]. 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].
KEY POINT |
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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
All Recommendations
Reviewed and updated: Hector I. Ojeda-Martinez, MD, with the Medical Care Criteria Committee; May 21, 2021
ALL RECOMMENDATIONS: PREVENTION AND MANAGEMENT OF HEPATITIS A VIRUS INFECTION IN ADULTS WITH HIV |
Pre-Exposure Vaccination
Post-Exposure Immune Globulin
Management of HAV/HIV Coinfection
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Guideline Information and Updates
Guideline Information | |
Intended users |
New York State clinicians in outpatient settings who provide primary and HIV specialty care for adults who have or are at risk of acquiring hepatitis A virus infection |
Last reviewed and updated |
May 21, 2021 |
Lead author |
Hector I. Ojeda-Martinez, MD |
Original publication |
August 2018 |
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 | |
Developer and funding |
New York State Department of Health AIDS Institute (NYSDOH AI) |
Development |
See Guideline Development and Recommendation Ratings Scheme, below. |
Updates | |
May 21, 2021 |
Hector I. Ojeda-Martinez, MD, with the MCCC:
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August 2018 |
MCCC:
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Guideline Development: New York State Department of Health AIDS Institute Clinical Guidelines Program | |
Developer | New York State Department of Health AIDS Institute (NYSDOH AI) Clinical Guidelines Program |
Funding Source | NYSDOH AI |
Program Manager |
Clinical Guidelines Program, Johns Hopkins University School of Medicine, Division of Infectious Diseases. See Program Leadership and Staff. |
Mission | To produce and disseminate evidence-based, state-of-the-art clinical practice guidelines that establish uniform standards of care for practitioners who provide prevention or treatment of HIV, viral hepatitis, other sexually transmitted infections, and substance use disorders for adults throughout New York State in the wide array of settings in which those services are delivered. |
Expert Committees |
The NYSDOH AI Medical Director invites and appoints committees of clinical and public health experts from throughout NYS to ensure that the guidelines are practical, immediately applicable, and meet the needs of care providers and stakeholders in all major regions of NYS, all relevant clinical practice settings, key NYS agencies, and community service organizations. |
Committee Structure |
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Conflicts of Interest Disclosure and Management |
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Evidence Collection and Review |
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Recommendation Development |
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Review and Approval Process |
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External Reviewers |
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Update Process |
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Recommendation Ratings Scheme | |||
Strength | Quality of Evidence | ||
Rating | Definition | Rating | Definition |
A | Strong | 1 | Based on published results of at least 1 randomized clinical trial with clinical outcomes or validated laboratory endpoints. |
B | Moderate | * | Based on either a self-evident conclusion; conclusive, published, in vitro data; or well-established practice that cannot be tested because ethics would preclude a clinical trial. |
C | Optional | 2 | Based on published results of at least 1 well-designed, nonrandomized clinical trial or observational cohort study with long-term clinical outcomes. |
2† | Extrapolated from published results of well-designed studies (including nonrandomized clinical trials) conducted in populations other than those specifically addressed by a recommendation. The source(s) of the extrapolated evidence and the rationale for the extrapolation are provided in the guideline text. One example would be results of studies conducted predominantly in a subpopulation (e.g., one gender) that the committee determines to be generalizable to the population under consideration in the guideline. | ||
3 | Based on committee expert opinion, with rationale provided in the guideline text. |