Sex: U
Vaccine: HEPA, HEPA
Symptoms: Headache, Hepatitis A, Hepatitis A antibody positive, Hepatitis A virus test positive, Hepatitis B surface antigen negative
Clinical narrative: Vaccination failure; Hepatitis A infection; Fatigue; Headache; Fever; Dark urine; This case was reported in a literature article and described the occurrence of vaccination failure in a 55-year-old other patient who received Hepatitis A vaccine for prophylaxis.   Co-suspect products included Hepatitis A vaccine for prophylaxis.   Concurrent medical conditions included hiv infection. Concomitant products included abacavir, lamivudine and dolutegravir.   On an unknown date, the patient received the 1st dose of Hepatitis A vaccine and Hepatitis A vaccine. On an unknown date, more than 2 years after receiving Hepatitis A vaccine and Hepatitis A vaccine, the patient experienced vaccination failure (serious criteria hospitalization and GSK medically significant), acute hepatitis a (serious criteria hospitalization), fatigue (serious criteria hospitalization), headache (serious criteria hospitalization), fever (serious criteria hospitalization) and dark urine (serious criteria hospitalization). On an unknown date, the outcome of the vaccination failure was unknown and the outcome of the acute hepatitis a, fatigue, headache, fever and dark urine were recovered/resolved.   The reporter considered the vaccination failure, acute hepatitis a, fatigue, headache, fever and dark urine to be related to Hepatitis A vaccine and Hepatitis A vaccine.  Additional details were reported as follows: This case was reported in a literature article and described the vaccination failure in a 55 years old transgender female patient who was vaccinated with unspecified Hepatitis A vaccine (manufacturer unknown) for prophylaxis.  [Since 1st January 2019, 2 separate acute hepatitis A (HAV) outbreaks had identified spreading mainly via person-to-person transmission: (1) a small outbreak primarily among men who had sex with men (MSM; November 2018 to March 2019) and (2) a large outbreak beginning in April 2019, primarily among persons experiencing homelessness (PEH) or persons who use drugs (PWUD). The authors described 4 people with HIV (PWH) who acquired acute hepatitis A (HAV) infection during recent outbreaks despite documented immunity and/or vaccination. The authors identified patients with acute HAV infection during outbreak surveillance within the above noted outbreaks. Coauthors on this report initiated a discussion with local public health collaborators when some coauthors identified 2 of these cases through direct patient care at the hospital. The authors gathered data from surveillance records, case report forms, and medical records via existing public health and electronic medical records data systems]. The patient had male sex at birth. The patient had housing in a private stable single apartment. The patient had no known prior HAV infection and documented past immunity (via qualitative HAV immunoglobulin G [IgG] positivity years after vaccination). The patient's sexual orientation was sex with men. The patient had condomless sex with a new male partner during their exposure period. The patient denied illicit drug use. The patient was unemployed. The patient had diagnosed to HIV (Human immunodeficiency virus) 28 years (between HIV and HAV diagnosis). The patient's CD4 cell count nadir was unknown. The patient's HIV viral load (VL) history was undetectable viral load (since unknown date). The patient had been taking antiretroviral medication (at time of HAV diagnosis) as abacavir, lamivudine, dolutegravir. No information on patient's family history was provided. On an unspecified date, 12 years and 6 years prior to HAV infection, the patient received two doses of unspecified Hepatitis A vaccine (administration route and site unspecified; dosage unknown; batch number not provided) respectively. [The patient received the two doses 12 and 6 years prior to HAV infection]. On an unspecified date, the patient's CD4 cell count at HAV vaccination was 333 cells/mL. The patient's HAV IgG positivity was not known. The patient's autoimmune workup showed antinuclear antibody (ANA) was negative 12 years prior. The patient's CD4 cell count was 1013 cells/mL and HIV VL was undetectable within year before HAV diagnosis. On an unspecified date, between January 2019 and June 2020, an unknown period after the vaccination, the patient presented with 10 days of fatigue, headache, fever and dark urine. The patient required hospitalization due to HAV infection. The patient had likely source of acute HAV acquisition was condomless receptive anal sex with new, consistent male partner for 2 months prior. The patient's liver function tests (LFT) peak showed aspartate aminotransferase/alanine aminotransferase (AST/ALT) was 538/1090 units/litre and total bilirubin was 6.0 units/litre. The patient had no radiologic findings. The patient's hepatitis C virus (HCV) antibody (Ab) was negative. Other workup showed hepatitis B surface antigen (HBV sAg) was negative, Cytomegalovirus (CMV) was not known, and Herpes Simplex virus (HSV) was not known. The patient's sexual transmitted infection (STI) testing at admission showed rapid plasma regain (RPR) positive (titer 1:32); Urine gonorrhea (GC)/Chlamydia (CT) nucleic acid amplification test (NAATs) was negative. The patient's HAV IgM at admission was positive (Positive if more than 1.0 (s/co)). The patient's HAV IgG at presentation was not known. The patient's HAV PCR was positive at admission. The patient was consistently engaged in HIV care and adherent to antiretrovirals (ARVs). The patients' liver function and subjective symptoms improved quickly with supportive care. The patient was discharged to home and returned to their baseline health status.  This case was considered serious due to hospitalization and vaccination failure. The authors commented, "All 4 PWH presented here acquired acute HAV requiring hospitalization despite documented immune response after vaccination and/or prior documentation of HAV vaccination at CD4 more than 200 cells/mL. Several factors may account for HAV infection despite presumed immunity. First, we know that protective immunity may wane over time and lead to disease acquisition and that immunosuppressed states, such as HIV, may predispose individuals to less durable immunity. Vaccination at a CD4 count more than 200 is thought to predict long-lasting immunity in PWH. Despite that, the patients in our case series were either vaccinated at a CD4 count more than 200 (Patient D) or had well-controlled HIV with long-standing undetectable HIV viral loads at the time of HAV vaccination (Patients A-C). Therefore, it is unlikely that secondary failures correlate with profound immune suppression at the time of vaccination in these patients. Accordingly, the reliance on CD4 count alone as an indicator of who will benefit from an HAV booster vaccination is insufficient. Second, a past or current positive HAV IgG titer may be an unreliable correlate of protection from acute HAV infection in PWH. Neutralizing anti-HAV IgG titers, which are thought to be associated with lifelong protection, are significantly lower after inactivated HAV vaccination as compared with natural infection. Total HAV IgG titers are correlated with neutralizing antibody titers where a level of more than 10 mIU/mL is considered a surrogate correlate of protection in vaccine trials. However, a minimum anti-HAV IgG level that confers protection in real-world situations has not been established. Three patients in our series (A-C) had positive HAV IgG titers both at the time of acute HAV infection and 3-8 years prior, which is consistent with their prior vaccination, although, admittedly, acute infection may have boosted HAV IgG titers. Further study is required to define the mechanisms of these secondary failures and may inform whether the traditional surrogate markers of immunity (ie, more than or equal to 10 mIU/mL anti-HAV IgG) should be modified for PWH. Possible mechanisms of these "breakthrough" infections could include a large inoculum related to unprotected anal intercourse, particularly with oral-anal sex, or viral escape phenomenon overcoming any existing immunity. Third, self-reported, and even well-documented, complete HAV vaccination may not be evidence of sufficient protection during an outbreak. Given the limitations of using CD4 monitoring, HAV IgG titers, and vaccination history to predict protection from acute HAV in PWH, we suggest that HAV booster vaccination be considered, especially during a local outbreak, based on risk factors for HAV acquisition irrespective of documented prior vaccination or immunity. The risk of HAV infection is higher in MSM; as such, it is possible that anal intercourse, particularly anal-oral sex, delivers a larger HAV inoculum or at least increases rates of fecal-oral transmission as compared with other exposures. In our series, Patients A to C were MSM, and Patient D identified as a transgender woman (male at birth) with similar sexual risk factors for HAV infection. Of note, a limitation of our report is the lack of risk factor analysis with comparator groups, such as persons within the local HAV outbreak not living with HIV. However, no foodborne transmission risk factors were identified in the patients reported in this series. These 4 cases serve as "proof of concept" that some form of prior immunity is not protective against acute HAV infection during local outbreaks among PWH. As such, we posit that certain sexual behaviors historically associated with MSM, such as anal-penile sex or anal-oral sex, reported by PWH should prompt consideration of an HAV booster vaccination during a local outbreak. HAV risk factors, such as homelessness (PEH), drug use (PWUD), and predisposing sexual behaviors, often coexist within individual patients and patient populations. A comprehensive social history, including a detailed history of drug use and specific sexual behaviors, will help clinicians identify PWH who may benefit from booster vaccination during an outbreak. Single booster vaccination has been shown to generate sufficient immune response in PWH. Logistical considerations, such as supply or administration during the coronavirus disease 2019 pandemic, must also be accounted for in future public health policy regarding HAV booster vaccination".  This article corresponding to this case is not available for regulatory submission due to copyright restriction. This case is 1 of the 4 cases reported in the literature article.; Sender's Comments:  US-GLAXOSMITHKLINE-US2021GSK232965:Same reporter US-GLAXOSMITHKLINE-US2021GSK232999:Same reporter US-GLAXOSMITHKLINE-US2021GSK233001:Same reporter