Evidence to Recommendations for Use of Hepatitis A Vaccine for Persons With HIV

• PWHIV are at increased risk of HAV infection.
  • HIV infection can lead to an immunocompromised state
  • PWHIV are frequently less likely to be vaccinated for a variety of reasons (missed opportunities for vaccination, lack of access to health care, etc.).
• Outbreaks that include PWHIV can have prolonged HAV transmission.
  • HAV viremia in PWHIV tends to be higher and more durable.

• In 2015, there were an estimated 1.12 million PWHIV in the United States (1).
• HIV co-infection outbreak data are available for a limited number of states.
  • Among 249 reported cases of hepatitis A in Tennessee, 11 (4%) patients were PWHIV (6).
  • Among 359 reported cases of hepatitis A in Massachusetts, 4% were PWHIV (as of June 5, 2019) (7).
  • Among 85 reported cases of hepatitis A in Illinois, 7 (8.2%) were PWHIV (as of June 5, 2019) (8).

• Infectious Diseases Society of America recommends vaccinating all PWHIV against HAV infection as part of their guidelines (9). Eleven other manuscripts described routinely vaccinating PWHIV as part of clinical practice (10–20).
• Spain, Italy, and Australia report routinely vaccinating all PWHIV against HAV infection.

• HAV infection may increase HIV replication, potentially increasing potential for HIV transmission.
• HAV viremia in PWHIV tends to be higher, more durable, and can lead to a longer transmission period.
• HepA vaccine is a highly effective vaccine in the general population.
  • Seroconversion rates in PWHIV are 48.5%–94% (2–4). Higher rates of response among PWHIV to vaccination were associated with higher baseline median CD4+ count at vaccination and/or lower HIV viral load.

• Over 20 years of safety monitoring have shown no safety concerns (CDC, unpublished).
• Similar rates of serious adverse events have been observed in PWHIV vs. HIV-negative persons.
  • No unexpected vaccine adverse events were reported among PWHIV from 1990 to 2016.
• HepA vaccine does not increase HIV viral load, affect CD4 cell count, or accelerate progression to acquired immunodeficiency syndrome (AIDS).

• Although seroconversion rates among PWHIV are lower following vaccination compared to the HIV-negative population, seroprotection against HAV infection in PWHIV can be achieved.
• Out of 130 PWHIV, 89% maintained seropositivity 6–10 years after a two-dose vaccine series (21).
  • Vaccination at higher CD4+ counts is associated with better vaccine-induced immune response.

Safety of the intervention is Level 3 (Low)

• The benefit outcome, reduction in hepatitis A infection, among randomized controlled trials (RCTs) was graded as EVIDENCE TYPE 2.
  • We downgraded for indirectness due to variability of hepatitis A antibody seroconversion thresholds used.
• The benefit outcome, reduction in hepatitis A infection, among observational studies was graded as EVIDENCE TYPE 4.
  • We downgraded for indirectness due to variability of hepatitis A antibody seroconversion thresholds used and for risk of bias due to limited studies comparing a 2-dose standard intervention to no vaccine.
• The harm outcome, mild adverse events, among RCTs was graded as EVIDENCE TYPE 1.
• The harm outcome, mild adverse events, among observational studies was graded as EVIDENCE TYPE 3.
• The harm outcome, serious adverse events, among RCTs was graded as EVIDENCE TYPE 3.
  • We downgraded for very serious imprecision due to small study population size.
• The harm outcome, serious adverse events, among observational studies was graded as EVIDENCE TYPE 4.
  • We downgraded indirectness for use of multiple non-hepatitis A vaccines and for imprecision due to small study population size.

• Few studies have been conducted to investigate PWHIV preferences regarding HAV infection.
• Reasons for non-vaccination (22):
  • Not recommended by providers
  • Lack of expected effectiveness
  • Fear of vaccine adverse effects

• Few studies have been conducted specifically to determine the value PWHIV assign to protection against HAV.
• Among people who use injection drugs from five U.S. cities (24.2% of whom were PWHIV) (23), convenience was the important determining factor for initiating HepA/hepatitis B (HepB) vaccination.

• The proposed recommendation parallels ACIP recommendations for HepB vaccination in PWHIV.
  • Similarly lower seroresponses have been observed after HepB vaccine administration among PWHIV with low CD4+ counts.
• ACIP currently recommends that all HIV patients receive their first dose of HepB vaccine during their first HIV care visit after having their hepatitis B virus serologies drawn.
  • This option is safe and effective for PWHIV and less confusing for providers.

• Adult HepA vaccines are licensed only for certain high-risk groups, and cost effectiveness data on vaccine use for these indications are limited.
• Outbreaks and subsequent response efforts incur medical costs, productivity losses, disruption of other public health services, and diversion of public health resources and extensive human resources.
  • Cost of an outbreak among people who use injection drugs (n = 590, Washington): $3.3 million (24).
  • Cost of an outbreak among MSM (n = 136, Ohio): $520,039 (24).
  • The cost of routine immunization through HIV and primary care clinics may be lower per capita than the cost of large, rapid vaccination campaigns for outbreak response.

• Vaccine response improves if individuals are vaccinated earlier in the course of HIV infection, when they tend to have higher initial CD4+ counts and lower HIV RNA viral loads.
• Despite existing recommendations to vaccinate based on specific risk factors, there is inadequate screening and vaccination for HAV among PWHIV, even in HIV clinics.
  • In a US study, 23.3% of eligible outpatient PWHIV received 1 dose of HepA vaccine (25).
  • In a British study, HepA vaccine was indicated in 75% of PWHIV, but had been delivered to only 36% of eligible individuals (26).