Question: Should routine two-dose* vaccination to prevent hepatitis A virus infection be given to HIV-positive persons?

Population: Adult HIV-positive persons 

Intervention: Routine two-dose* hepatitis A vaccination

Comparison(s): No routine two-dose* hepatitis A vaccination

Outcomes: 

• Hepatitis A infection

• Mild adverse events

• Serious adverse events

*Or three-dose vaccination when a combination vaccine is used.

Background: 

In 2015, there were an estimated 1.12 million persons with HIV (PWHIV) in the United States (1). When PWHIV are coinfected with hepatitis A virus (HAV), they experience higher peak HAV viral loads and a prolonged duration of hepatitis A 

viremia compared to persons without HIV infection, and are therefore more likely to transmit HAV. HAV co-infection may 

increase HIV viral load, potentially also increasing HIV transmission. PWHIV respond to hepatitis A (HepA) vaccine with 

seroconversion rates of 48.5%–94.0% (2,3,4) following a 2-dose monovalent vaccination schedule; factors associated with a 

protective antibody response in PWHIV include a CD4+ cell count above 200/μl and a low HIV RNA viral load. 

The Advisory Committee on Immunization Practices (ACIP) currently recommends HepA vaccine for groups at increased risk 

of HAV or severe HAV infection, but does not specify PWHIV as a risk group. The groups currently indicated for HepA vaccine 

include persons traveling to or working in countries that have high or intermediate endemicity of infection, men who have sex 

with men (MSM), persons who use injection or non-injection drugs, persons with clotting-factor disorders, persons who have 

occupational risk for infection, persons who anticipate close personal contact with an international adoptee, persons with 

chronic liver disease, and persons experiencing homelessness. The Medical Monitoring Project (5), which samples PWHIV in 

the United States and collects clinical and behavioral information, estimates that 59.9% (95% CI: 57.3–62.4) of PWHIV had 

one of the following indicators: male-to-male sexual contact in the past 12 months, injection or non-injection drug use in the 

past 12 months, experiencing homelessness in the past 12 months, chronic liver disease, or a clotting factor disorder. Data 

were not available for proportions of PWHIV who have occupational risk for infection, who travel, or who have close contact 

with an international adoptee; excluding these groups, 40.1% (95% CI: 37.6–42.7%) of PWHIV in the United States do not 

have a known ACIP-recommended indication for HepA vaccine.

From January 2017 to February 2019, more than 12,500 cases of HAV infection in the United States were associated with 

person-to-person transmission in multiple states. HIV co-infection data are available for these cases from a limited number of 

https://www.cdc.gov/vaccines/acip/recs/grade/hep-a-hiv-etr-h.pdf 7/17/2020
states. Among 249 reported HAV cases in Tennessee, 11 (4%) patients were PWHIV (6). Six (55%) of these 11 HAV/HIV coinfected patients received partial or complete HepA vaccination prior to acute hepatitis A infection. There were no identified 

cases of breakthrough acute hepatitis A infection in previously vaccinated persons not infected with HIV. The data from 

Tennessee and reports from other HAV outbreak–associated states indicate a need to include PWHIV as an indication for 

HepA routine vaccination, and potentially for additional prophylaxis after a potential exposure to HAV.

Additional background information supporting the ACIP recommendations on the use of HepA vaccine can be found in the relevant 

publication of the recommendation referenced on the ACIP website.

CRITERIA WORK GROUP JUDGMENTS EVIDENCE ADDITIONAL INFORMATION

PROBLEM

Is the problem 

of public health 

importance?

No Probably

no

Uncertain Probably

yes

Yes Varies

X

 PWHIV are at increased risk of

HAV infection.

– HIV infection leads 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.

o Among 249 reported cases of

hepatitis A in Tennessee, 11

(4%) patients were PWHIV

(6).

 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.
o Among 359 reported cases of 

hepatitis A in Massachusetts, 

4% were PWHIV (as of June 5, 

2019) (7).

o Among 85 reported cases of 

hepatitis A in Illinois, 7 (8.2%) 

were PWHIV (as of June 5, 

2019) (8).

BENEFITS & HARMS 

How 

substantial are 

the desirable 

anticipated 

effects?

Minimal Small Moderat

e

Large Don’t 

know

Varies

X

 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.

CRITERIA WORK GROUP JUDGMENTS RESEARCH EVIDENCE ADDITIONAL INFORMATION

How 

substantial are 

the 

undesirable 

anticipated 

effects?

Minimal Small Moderate Large Don’t 

know

Varies

X

 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 or CD4+ cell count, nor 

does it speed progression to AIDS.

Do the 

desirable 

effects 

outweigh the 

undesirable 

effects?

Favors 

intervention

Favors 

comparison

Favors 

both

Favors 

neither

Unclear

X

 Although seroconversion rates 

among PWHIV are lower following 

vaccination compared to the HIVnegative 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.

What is the 

overall 

certainty of 

this evidence 

for the critical 

outcomes?

Effectiveness of the intervention

No

included

studies

4 

Very low

3 

Low

2

Moderate

1

High

X

Safety of the intervention

No

included

studies

4

Very low

3

Low

2

Moderate

1

High

X

Please refer to GRADE (safety and 

effectiveness) tables for detailed 

assessment of the certainty of the evidence. 

For more information, please see the ACIP 

Handbook for Developing Evidence-Based 

Recommendations.

• 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 

Due to these vaccines’ 

long-term safety record, 

and lack of any significant 

adverse safety signal in 

the Vaccine Adverse Event 

Reporting System or in the 

literature, the workgroup 

was confident in the safety 

of this vaccine in this 

population.
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 nonhepatitis A vaccines and for 
imprecision due to small 

study population size. 

VALUES

Does the target 

population feel 

that the 

desirable 

effects are 

large relative 

to undesirable 

effects?

No Probably

no

Uncertain Probably

yes

Yes Varies

X

 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

CRITERIA WORK GROUP JUDGMENTS RESEARCH EVIDENCE ADDITIONAL INFORMATION

Is there 

important 

uncertainty 

about or 

variability in 

how much 

people value 

the main 

outcomes?

Important uncertainty or variability

Possibly important uncertainty or variability

Probably no important uncertainty or 

variability

X

No important uncertainty or variability

No known undesirable outcomes

• 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.

ACCEPTABILITY

Is the 

intervention 

acceptable to 

key 

stakeholders?

No Probably

no

Uncertain Probably

yes

Yes Varies

X

 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.

RESOURCE USE

Is the 

intervention a 

reasonable and 

efficient 

allocation of 

resources?

No Probably no Uncertain Probably yes Yes

X

 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.

A true cost-effectiveness 

analysis has not been 

performed.
FEASIBILITY

Is the 

intervention 

feasible to 

implement?

No Probably

no

Uncertain Probably

yes

Yes Varie

s

X

 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).

Simplifying provider 

guidance may improve 

protection of at-risk 

PWHIV.

Balance of 

consequences

Undesirable 

consequences 

clearly outweigh

desirable 

consequences

in most settings

Undesirable 

consequences 

probably outweigh

desirable 

consequences

in most settings

The balance 

between 

desirable and 

undesirable 

consequences 

is closely balanced 

or uncertain

Desirable 

consequences 

probably outweigh 

undesirable 

consequences

in most settings

X

Desirable 

consequences 

clearly outweigh

undesirable 

consequences

in most settings

There is 

insufficient 

evidence to 

determine the 

balance of 

consequences

Is there sufficient information to move forward with a recommendation?

Yes X No 
Policy Options for 

ACIP Consideration

ACIP does not recommend the 

intervention

ACIP recommends the intervention for 

individuals based on shared clinical 

decision-making

ACIP recommends the intervention

X

Recommendation 

(text)

All persons with HIV aged 1 year and older should be routinely vaccinated against hepatitis A. 

Additional 

considerations

(optional)

Final deliberation and decision by the ACIP

Final ACIP 

recommendation

ACIP does not recommend the 

intervention

ACIP recommends the intervention for 

individuals based on shared clinical 

decision-making

ACIP recommends the intervention

X

ACIP considerations All persons with HIV aged 1 year and older should be routinely vaccinated against hepatitis A. 
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