Grading of Recommendations Assessment, Development, and Evaluation (GRADE): Meningococcal 

Conjugate Vaccines in HIV-Infected Persons

Introduction

A growing body of evidence demonstrates an increased risk of meningococcal disease among HIVinfected persons; risk increasesfurtherwith a low CD4 count or high viral load (1-3). Meningococcal 

vaccination has previously been recommended for certain groups with medical conditions that increase 

risk for meningococcal disease (4), including persons with persistent complement component 

deficiencies, persons receiving eculizumab (Soliris®, Alexion Pharmaceuticals), or persons with functional 

or anatomic asplenia. Three meningococcal conjugate vaccines are licensed for use in the United States: 

two quadrivalent (serogroups A, C, W, and Y) vaccines (MenACWY-D [Menactra®, Sanofi Pasteur] and 

MenACWY-CRM [Menveo®, GlaxoSmithKline]) and one bivalent (serogroups C and Y) vaccine (HibMenCY-TT [MenHibrix®, GlaxoSmithKline]). 

GRADE was used to evaluate routine vaccination of HIV-infected persons with meningococcal conjugate 

vaccine. The primary policy question was “Should meningococcal conjugate vaccines be administered 

routinely to all HIV-infected persons aged ≥2 months for prevention of meningococcal disease?”

Evidence of benefits and harms were reviewed in accordance with GRADE methods (5). 

Methods for GRADE

Immunogenicity and safety data from two open-label observational studies of MenACWY-D (6-8) were 

considered in the assessment.No studies of immunogenicity or safety of MenACWY-CRM or Hib-MenCYTT in HIV-infected persons were available.

The benefits outcomes considered for each vaccine included short-term immunogenicity (1 month after 

both the first dose of vaccine [week 4] and after the second dose of vaccine [week 28]) and persistence 

of immunogenicity (48weeks after the second dose of vaccine [week 72]). The harms outcome

considered included occurrence of serious adverse events(SAEs) after vaccination. The evidence type 

for each outcome was derived through a review of study design, risk of bias, inconsistency, indirectness, 

imprecision and other considerations (strength of association, dose response gradient and opposing 

plausible residual confounding or bias). 

Clinical effectiveness studies of meningococcal vaccines among HIV-infected persons are not feasible 

because of low incidence of disease. Estimates of short-term immunogenicity and persistence of 

immunogenicity were based on demonstration of immune response, as measured by serum bactericidal 

assay using a baby rabbit complement source (rSBA) against each meningococcal serogroup (A, C, W, 

https://www.cdc.gov/vaccines/acip/recs/grade/mening-vac-hiv.pdf 4/26/2017 
and Y). Immunogenicity was assessed by the proportion of subjects who achieved a ≥4-fold increase in 

rSBA titer for each of the strainstested and the proportion of subjects who achieved an rSBA titer 

≥1:128.

Results:

Table 1: Evidence Table: Use of MenACWY vaccinesin HIV-infected persons aged ≥2 months 

Outcomes Design

(# studies)

Initial 

Evidence

Risk of 

Bias Inconsistency Indirectness Imprecision Publication Bias Others Final Evidence

Overall 

Evidence 

Type

Benefits

3 

Short-term 

immunogenicity after 

1 dose (week 4)

2 Obs 3 

Not 

Serious Not Serious Serious *(-1) Not Serious

Not 

Serious

Yes §ǁ

(+1) 3 

Short-term 

immunogenicity after 

2 doses(week 28)

2 Obs 3 

Not 

Serious Not Serious Serious *(-1) Not Serious

Not 

Serious

Yes §ǁ

(+1) 3 

Persistence of 

immunogenicity after 

2 doses (week 72)

2 Obs 3 Not 

Serious Not Serious Serious *(-1) Not Serious Not Serious

Yesǁ

(+1) 3 

Harms

Serious adverse 

events (after any 

dose)

2 Obs 3 Not 

serious

Not serious Not Serious Serious ‡(-1) Not 

Serious

None 4 

*SBA titers for serogroups A C W Y not well-defined correlate of protection in HIV-infected persons ‡Total sample size not sufficient to detect rare adverse events

§Very strong strength of association: relative risk ranges between 5 and 49

ǁStrong dose response

Table 1b: Considerations for Vaccine Use: MenACWY vaccines in HIV-infected persons aged ≥2 months 

Key Factors Comments

Balance between benefits 

and harms

Vaccine is immunogenic in HIV-infected children and adolescents in the shortterm and safe. Immunogenicity persists in HIV-infected children but wanes 

rapidly in adolescents and young adults. Immune responses are suppressed 

with lower CD4 percentage and higher viral loads. Low disease burden lowers 

overall benefits.

Evidence type for benefits and harms

MenACWY vaccines in HIVinfected persons aged ≥2 

months

Overall Evidence Type: 3

Benefits:

Short term immunogenicity after 1 dose (week 4): Evidence Type 3

Short term immunogenicity after 2 doses (week 28): Evidence Type 3

Persistence in immunogenicity (week 72): Evidence Type 3

Harms:

Serious Adverse Events: Evidence Type 4

https://www.cdc.gov/vaccines/acip/recs/grade/mening-vac-hiv.pdf 3/12/2019 
Summary: 

The evidence type for use of meningococcal conjugate vaccine in HIV-infected persons aged ≥2 months 

was determined to be type 3 (low level of evidence). After reviewing the result of the GRADE analysis

and other data demonstrating increased risk of meningococcal disease among HIV-infected persons, the 

Advisory Committee on Immunization Practices (ACIP) recommended thatHIV-infected persons aged ≥2 

months be routinely vaccinatedwith a MenACWYvaccine to preventmeningococcal disease

(recommendation Category A). The full recommendations for the use of MenACWYvaccines in HIVinfected persons aged ≥2 months are available on the ACIP website. 

References

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meningococcal disease in HIV-infected individuals associated with higher case-fatality ratios in South 

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2. Miller L, Arakaki L, Ramautar A, Bodach S, Braunstein SL, Kennedy J, et al. Elevated risk for invasive 

meningococcal disease among persons with HIV. Annals of internal medicine. 2014 Jan 7;160(1):30-7.

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meningococcal disease in children and adults with HIV in England: a population-based cohort study. BMC 

Med. 2015;13:297.

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5. ACIP. Evidence-Based Recommendations--GRADE. 2015 [July 2015]; Available from: 

http://www.cdc.gov/vaccines/acip/recs/GRADE/about-grade.html. 

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Immunogenicity and safety of 1 vs 2 doses of quadrivalent meningococcal conjugate vaccine in youth 

infected with human immunodeficiency virus. J Pediatr. 2012 Oct;161(4):676-81 e2.

https://www.cdc.gov/vaccines/acip/recs/grade/mening-vac-hiv.pdf 3/12/2019