Immunizations for Adults with HIV

Immunizations for Adults with HIV

Medical Care Criteria Committee, April 2018

Purpose of this Document

This compendium of immunization recommendations for adults (≥18 years) with HIV who are not pregnant was compiled by the New York State (NYS) Department of Health (DOH) AIDS Institute (AI) to assist clinical practitioners in NYS who provide primary care to adults with HIV. The goal is to present in one easy-to-use document all of the routine vaccinations recommended for adults with HIV by the Centers for Disease Control and Prevention (CDC), National Institutes of Health (NIH), HIV Medicine Association (HIVMA) [AIDSinfo 2017], and the Infectious Disease Society of America [Rubin et al. 2014]. The European AIDS Clinical Society guidelines were also consulted [EACS 2017]. Where a recommendation differs from these source documents, the NYSDOH AI rationale is provided. This document integrates 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 NYS by the end of 2020.

Immunizations against infectious diseases are a particularly important component of care for individuals with HIV. Immunodeficiency reduces natural defenses to vaccine-preventable diseases in people with HIV and places them at increased risk for disease and for severe disease [Crum-Cianflone and Wallace 2014; Rubin et al. 2014]. However, there is concern that patients with HIV-associated immunodeficiency may not be able to mount and maintain an appropriate immune response to vaccines and may be harmed by live virus vaccines. The strength of the immune response may be lower in patients with more advanced HIV, especially among those with CD4 counts <200 cells/mm3 and/or HIV viral load >200 copies/mL, and shorter in duration than in adults without HIV [Crum-Cianflone and Wallace 2014]. Immunogenicity, vaccine response monitoring, and requirements for additional booster doses for patients with HIV are discussed on pages for individual vaccines.

Development of this document: This reference was compiled by the NYSDOH AI Clinical Guidelines Program, which is a collaborative effort between the NYSDOH AI Office of the Medical Director and the Johns Hopkins University School of Medicine, Division of Infectious Diseases.

The goal of the Clinical Guidelines Program, established in 1986, is to develop and disseminate evidence-based, state-of-the-art clinical practice guidelines to improve the quality of care provided to people with HIV, hepatitis C virus infections, and sexually transmitted infections and to improve drug-user health and LGBT health throughout NYS. NYSDOH AI guidelines are developed by committees of clinical experts through a consensus-driven process.

The NYSDOH AI Medical Care Criteria Committee is charged with developing evidence-based clinical recommendations for clinicians in NYS who treat adults with HIV. The recommendations in this document, with the exception of one, are the same as those of the CDC/NIH/HIVMA guidelines. This document also discusses published literature related to specific vaccines and the rationale for recommendations for which there is no consensus among the referenced guidelines, no evidence specific to patients with HIV, or new data have been published.

References

AIDSinfo. Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: Recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. 2017 Jul 6. https://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf [accessed 2018 Mar 27]

Crum-Cianflone NF, Wallace MR. Vaccination in HIV-infected adults. AIDS Patient Care STDS 2014;28(8):397-410. [PMID: 25029589]

European AIDS Clinical Society (EACS). Guidelines Version 9.0. 2017 Oct. http://www.eacsociety.org/files/guidelines_9.0-english.pdf [accessed 2018 Mar 27]

Rubin LG, Levin MJ, Ljungman P, Davies EG, Avery R, Tomblyn M, Bousvaros A, Dhanireddy S, Sung L, Keyserling H, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis 2014;58(3):e44-100. [PMID: 24311479]

Considerations and Contraindications

Medical Care Criteria Committee, April 2018

The tables and accompanying discussion in this section compile recommendations from the Centers for Disease Control and Prevention (CDC), National Institutes of Health, and HIV Medicine Association guidelines on immunization of adults with HIV who are not pregnant, along with vaccination schedules, clinical comments, and sources. The only recommendation in this guideline that was developed by the HIV Clinical Guidelines Program Medical Care Criteria Committee is in the section on zoster vaccination. Table 14 compiles all immunization recommendations into one printable table.

Inactivated vaccines are generally considered safe, although insufficient data exist to rule out rare adverse effects [ACIP 2011; Rubin et al. 2014]. Live, attenuated vaccines are contraindicated for patients with CD4 counts <200 cells/mm3 because of the risk of severe reactions in the setting of immunosuppression [Davis et al. 1977; CDC 1985, 1996; Redfield et al. 1987]. For patients with HIV who have CD4 counts ≥200 cells/mm3, inactivated forms of vaccines, such as polio, influenza, typhoid, and zoster are preferred over the live vaccine options. Live, attenuated vaccines should be administered only when an inactivated version does not exist and when the risk of the disease clearly outweighs the theoretical risk of vaccination.

KEY POINT: USE OF LIVE ATTENUATED VACCINES
  • Patients with CD4 count <200 cells/mm3: The following live, attenuated vaccines are contraindicated: Bacillus Calmette-Guérin; measles, mumps, rubella; oral typhoid; rotavirus*; varicella; yellow fever; zoster.
  • Patients with CD4 count ≥200 cells/mm3Use live, attenuated vaccines only if an inactivated alternative is not available and the risk of disease is greater than the risk of vaccination.

*Patient education: Patients with HIV should avoid handling diapers of infants vaccinated for rotavirus in the previous 4 weeks and all household members should wash their hands after changing diapers of an infant recently vaccinated for rotavirus.

Transient increases in viral load and decreases in CD4 cell count due to immune system activation have been described after vaccination in patients with HIV in some older studies [Rey et al. 2000; Kolber et al. 2002]. The changes are less likely to occur in patients taking antiretroviral therapy (ART) and have not been found to have long-term negative effects [Sullivan et al. 2000; Rubin et al. 2014].

KEY POINTS
  • In people with HIV older than 5 years, effective ART is defined as ART taken for ≥6 months, with CD4 percentage ≥15% and CD4 count ≥200 cells/mm3 for ≥6 months [McLean et al. 2013].
  • Viral suppression is defined as HIV viral load <200 copies/mL.

Clinicians should advise their patients with HIV that their family members, close contacts, and other household members should receive all age-appropriate vaccinations, including an annual influenza vaccine, to reduce the patients’ exposure to vaccine-preventable diseases [Fiore et al. 2011; ACIP 2013; Rubin et al. 2014]. Live, attenuated virus vaccines may be safely administered to close contacts of persons with HIV, with specific precautions for varicella and rotavirus vaccines. Transmission of live, attenuated virus after vaccination is rare [Rubin et al. 2014]. However, patients with HIV who lack varicella immunity are advised to avoid direct contact with persons who develop a rash after varicella or zoster vaccination, and should not handle diapers of an infant recently vaccinated for rotavirus [Marin et al. 2007; Cortese and Parashar 2009; Fiore et al. 2011; Rubin et al. 2014].

Tables 1 through 13 (for each vaccine listed on the left) present the recommended immunizations for adults with HIV, followed by discussion of each. For complete vaccination recommendations, see the CDC Immunization Schedules and the vaccine manufacturers’ package inserts.

How to File a Claim With the Vaccine Injury Compensation Program
  • Tel: 1-800-338-2382
  • Website: hrsa.gov/vaccinecompensation
  • Address to file a claim: US Court of Federal Claims, 717 Madison Place, NW, Washington DC 20005
References

Advisory Committee on Immunization Practices (ACIP). General recommendations on immunization — recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2011;60(2):1-64. [PMID: 21293327]

Advisory Committee on Immunization Practices (ACIP). Prevention and control of seasonal influenza with vaccines. Recommendations of the Advisory Committee on Immunization Practices–United States, 2013-2014. MMWR Recomm Rep 2013;62(Rr-07):1-43. [PMID: 24048214]

Centers for Disease Control and Prevention (CDC). Disseminated Mycobacterium bovis infection from BCG vaccination of a patient with acquired immunodeficiency syndrome. MMWR Morb Mortal Wkly Rep 1985;34(16):227-228. [PMID: 3920493]

Centers for Disease Control and Prevention (CDC). Measles pneumonitis following measles-mumps-rubella vaccination of a patient with HIV infection, 1993. MMWR Morb Mortal Wkly Rep 1996;45(28):603-606. [PMID: 8676852]

Cortese MM, Parashar UD. Prevention of rotavirus gastroenteritis among infants and children: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2009;58(Rr-2):1-25. [PMID: 19194371]

Davis LE, Bodian D, Price D, Butler IJ, Vickers JH. Chronic progressive poliomyelitis secondary to vaccination of an immunodeficient child. N Engl J Med 1977;297(5):241-245. [PMID: 195206]

Fiore AE, Fry A, Shay D, Gubareva L, Bresee JS, Uyeki TM. Antiviral agents for the treatment and chemoprophylaxis of influenza — recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2011;60(1):1-24. [PMID: 21248682]

Kolber MA, Gabr AH, De La Rosa A, Glock JA, Jayaweera D, Miller N, Dickinson GM. Genotypic analysis of plasma HIV-1 RNA after influenza vaccination of patients with previously undetectable viral loads. AIDS 2002;16(4):537-542. [PMID: 11872996]

Marin M, Guris D, Chaves SS, Schmid S, Seward JF. Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2007;56(Rr-4):1-40. [PMID: 17585291]

McLean HQ, Fiebelkorn AP, Temte JL, Wallace GS. Prevention of measles, rubella, congenital rubella syndrome, and mumps, 2013: summary recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2013;62(Rr-04):1-34. [PMID: 23760231]

Redfield RR, Wright DC, James WD, Jones TS, Brown C, Burke DS. Disseminated vaccinia in a military recruit with human immunodeficiency virus (HIV) disease. N Engl J Med 1987;316(11):673-676. [PMID: 3821799]

Rey D, Krantz V, Partisani M, Schmitt MP, Meyer P, Libbrecht E, Wendling MJ, Vetter D, Nicolle M, Kempf-Durepaire G, et al. Increasing the number of hepatitis B vaccine injections augments anti-HBs response rate in HIV-infected patients. Effects on HIV-1 viral load. Vaccine 2000;18(13):1161-1165. [PMID: 10649616]

Rubin LG, Levin MJ, Ljungman P, Davies EG, Avery R, Tomblyn M, Bousvaros A, Dhanireddy S, Sung L, Keyserling H, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis 2014;58(3):e44-100. [PMID: 24311479]

Sullivan PS, Hanson DL, Dworkin MS, Jones JL, Ward JW. Effect of influenza vaccination on disease progression among HIV-infected persons. AIDS 2000;14(17):2781-2785. [PMID: 11125897]

Updates

June 2018

Zoster vaccine: Changes/insertions made on June 4, 2018, are indicated in red, below.

  • RZV provides strong protection against shingles and post-herpetic neuralgia. Currently, there are no data on efficacy immunogenicity specific to people with HIV; however, superior efficacy and longer duration of protection have been demonstrated among the elderly, and a recombinant vaccine is preferred people with HIV. In addition, immunogenicity and safety following a 3-dose schedule has been demonstrated among people with HIV infection [Berkowitz et al. 2015]. 
  • Note: RZV is administered IM in distinction to ZVL which is delivered by SQ injection [Shimabukuro et al. 2018] 
  • Two references added June 4, 2018:
    • Berkowitz EM, Moyle G, Stellbrink HJ, Schürmann D, Kegg S, El Idrissi M, Oostvogeis L, Heineman TC, Zoster-015 HZ/su Study Group. Safety and immunogenicity of an adjuvanted herpes zoster subunit candidate vaccine in HIV-infected adults: a phase 1/2a randomizedplacebo-controlled studyJ Infect Dis. 2015 Apr 15;211(8):1279-87. [PMID: 25371534]
    • Shimabukuro TT, Miller ER, Strikas RA, et al. Notes from the Field: Vaccine Administration Errors Involving Recombinant Zoster Vaccine — United States, 2017–2018. MMWR Morb Mortal Wkly Rep 2018;67:585–586. [PMID: 29795075]

Haemophilus Influenzae Type B Conjugate (Hib)

Medical Care Criteria Committee, April 2018

Table 1: Hib Vaccine
Trade Names Hiberix; ActHIB
Indications  Patients at risk of Hib infection (see CDC: Recommended Immunization Schedule for Adults Aged 19 Years or Older, United States 2018)
Administration  Administer according to the CDC Immunization Schedule for all adults at risk
Revaccination  None
Comments  Not routinely recommended for people with HIV in the absence of other risk factors (see the CDC Immunization Schedule)

Discussion: Hib vaccination is not routinely recommended for patients with HIV in the absence of other risk factors, such as anatomic or functional asplenia, sickle cell disease, or hematopoietic stem cell transplant, because there is a low risk of H. influenzae type b infection in adults with HIV [Briere et al. 2014; Rubin et al. 2014; CDC 2017]. Data on the safety and efficacy of the Hib vaccine among adults with HIV indicate a strong immune response, similar to that in adults without HIV, except among those with severe immunosuppression [Steinhoff et al. 1991; Kroon et al. 1997; Dockrell et al. 1999; MacLennan et al. 2016].

References

Briere EC, Rubin L, Moro PL, Cohn A, Clark T, Messonnier N. Prevention and control of haemophilus influenzae type b disease: recommendations of the advisory committee on immunization practices (ACIP). MMWR Recomm Rep 2014;63(Rr-01):1-14. [PMID: 24572654]

Centers for Disease Control and Prevention (CDC). Recommended Immunization Schedules for Adults. 2017 Feb 27. https://www.cdc.gov/vaccines/schedules/hcp/adult.html [accessed 2018 Mar 27]

Dockrell DH, Poland GA, Steckelberg JM, Wollan PC, Strickland SR, Pomeroy C. Immunogenicity of three Haemophilus influenzae type b protein conjugate vaccines in HIV seropositive adults and analysis of predictors of vaccine response. Vaccine 1999;17(22):2779-2785. [PMID: 10438047]

Kroon FP, van Dissel JT, Rijkers GT, Labadie J, van Furth R. Antibody response to Haemophilus influenzae type b vaccine in relation to the number of CD4+ T lymphocytes in adults infected with human immunodeficiency virus. Clin Infect Dis 1997;25(3):600-606. [PMID: 9314445]

MacLennan CA, Richter A, Hodson J, Faustini S, Birtwistle J, Whitelegg A, Chigiga J, Singo M, Walker-Haywood J, Mulugeta B, et al. Brief Report: Immunization of HIV-Infected Adults in the UK With Haemophilus influenzae b/Meningococcal C Glycoconjugate and Pneumococcal Polysaccharide Vaccines. J Acquir Immune Defic Syndr 2016;73(3):287-293. [PMID: 27163175]

Rubin LG, Levin MJ, Ljungman P, Davies EG, Avery R, Tomblyn M, Bousvaros A, Dhanireddy S, Sung L, Keyserling H, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis 2014;58(3):e44-100. [PMID: 24311479]

Steinhoff MC, Auerbach BS, Nelson KE, Vlahov D, Becker RL, Graham NM, Schwartz DH, Lucas AH, Chaisson RE. Antibody responses to Haemophilus influenzae type B vaccines in men with human immunodeficiency virus infection. N Engl J Med 1991;325(26):1837-1842. [PMID: 1683682]

Hepatitis A Virus (HAV)

Medical Care Criteria Committee, April 2018

Table 2: HAV Vaccine
Trade Names
  • HAV: Havrix; Vaqta
  • HAV inactivated + hepatitis B virus (HBV): Twinrix
Indications
  • Patients who: 1) are HAV IgG negative and at risk of HAV infection and related morbidity and mortality; 2) seek protection against HAV (see CDC: Recommended Immunization Schedule for Adults Aged 19 Years or Older, United States 2018)
  • At-risk populations, including men who have sex with men and people who:
    • Have chronic liver disease or conditions that can lead to chronic liver disease
    • Travel to countries with high or intermediate endemicity of infection
    • Use and inject illicit drugs
    • Live in a community experiencing an outbreak of HAV infection
    • Have a clotting-factor disorder
    • Are at occupational risk of HAV infection
Administration
  • Administer according to the CDC Immunization Schedule
  • Obtain HAV IgG at least 1 month after final dose of vaccination series to identify nonresponders
  • If immune reconstitution appears likely, then consider deferring until patient’s CD4 count >200 cells/mm3 [AIDSinfo 2017]
Revaccination Nonresponders to primary HAV vaccination series should be revaccinated [Aberg et al. 2014] and counseled to avoid exposure
Comments

Discussion: Among patients with HIV, the HAV vaccine is recommended for those at risk of HAV infection or those who wish to reduce their risk of HAV infection [CDC 2017; WHO 2017].

The reported rate of HAV antibody seroconversion after vaccination ranges from 49% to 96% [Fiore et al. 2006; Crum-Cianflone and Wallace 2014; Mena et al. 2015]. A long-term follow-up study reported that over 85% of those who seroconverted after vaccination had a sustained antibody response for 5 to 10 years [Crum-Cianflone et al. 2011; Cheng et al. 2017]. Although immunocompetent patients with HIV respond to the HAV vaccine nearly as well as patients without HIV, patients with lower CD4 cell counts are less likely to acquire protective levels of antibody [Fiore et al. 2006; Crum-Cianflone and Wallace 2014; Mena et al. 2015].

If a patient’s CD4 count is <200 cells/mm3 or the patient has symptomatic HIV, it is preferable to defer vaccination until several months after initiation of antiretroviral therapy to maximize the antibody response to the vaccine [AIDSinfo 2017]. HAV vaccination should not be deferred in patients who are unlikely to achieve an increased CD4 cell count (see NYSDOH AI HAV-HIV Coinfection Guideline).

Care providers should perform HAV IgG at least 1 month after final dose of vaccination series to identify nonresponders. Nonresponders to HAV vaccination should be revaccinated [Aberg et al. 2014] and counseled to avoid exposure to HAV because they remain susceptible to infection, although one recent small study reported that 31% of primary nonresponders (n = 16) subsequently seroconverted after completing the two-dose vaccination series [Cheng et al. 2017]. If patients are susceptible to both HAV and HBV, the combined HAV/HBV vaccine (three doses at 0, 1, and 6 months) can be used regardless of the patient’s immune status [Aberg et al. 2014].

References

Aberg JA, Gallant JE, Ghanem KG, Emmanuel P, Zingman BS, Horberg MA. Primary care guidelines for the management of persons infected with HIV: 2013 update by the HIV medicine association of the Infectious Diseases Society of America. Clin Infect Dis 2014;58(1):e1-34. [PMID: 24235263]

AIDSinfo. Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: Recommendations from the Centers for Disease Control and Prevention, the National Insitutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. 2017 Jul 6. https://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf [accessed 2018 Mar 27]

Centers for Disease Control and Prevention (CDC). Recommended Immunization Schedules for Adults. 2017 Feb 27. https://www.cdc.gov/vaccines/schedules/hcp/adult.html [accessed 2018 Mar 27]

Cheng A, Chang SY, Sun HY, Tsai MS, Liu WC, Su YC, Wu PY, Hung CC, Chang SC. Long-term Durability of Responses to 2 or 3 Doses of Hepatitis A Vaccination in Human Immunodeficiency Virus-Positive Adults on Antiretroviral Therapy. J Infect Dis 2017;215(4):606-613. [PMID: 28011921]

Crum-Cianflone NF, Wallace MR. Vaccination in HIV-infected adults. AIDS Patient Care STDS 2014;28(8):397-410. [PMID: 25029589]

Crum-Cianflone NF, Wilkins K, Lee AW, Grosso A, Landrum ML, Weintrob A, Ganesan A, Maguire J, Klopfer S, Brandt C, et al. Long-term durability of immune responses after hepatitis A vaccination among HIV-infected adults. J Infect Dis 2011;203(12):1815-1823. [PMID: 21606540]

Fiore AE, Wasley A, Bell BP. Prevention of hepatitis A through active or passive immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2006;55(Rr-7):1-23. [PMID: 16708058]

Mena G, Garcia-Basteiro AL, Bayas JM. Hepatitis B and A vaccination in HIV-infected adults: A review. Hum Vaccin Immunother 2015;11(11):2582-2598. [PMID: 26208678]

World Health Organization (WHO). Hepatitis A outbreaks mostly affecting men who have sex with men–European Region and the Americas. 2017 Jun 7. http://www.who.int/csr/don/07-june-2017-hepatitis-a/en/ [accessed 2018 Mar 27]

Hepatitis B Virus (HBV)

Medical Care Criteria Committee, April 2018

Table 3: HBV Vaccine
Trade names
  • HBV 2-dose series: HEPLISAV-B (see note in comments)
  • HBV 3-dose series: Engerix-B; Recombivax HB
  • Hepatitis A virus (HAV) inactivated + HBV: Twinrix
Indications Patients who are negative for anti-HBs and do not have chronic HBV infection (see CDC: Recommended Immunization Schedule for Adults Aged 19 Years or Older, United States 2018 and the NYSDOH AI guideline HBV-HIV Coinfection > Figure 3: Algorithm for HBV Pre-Vaccination Screening and Vaccination in Patients with HIV)
Administration
  • Administer according to the CDC Immunization Schedule for all adults [Schillie et al. 2018b]
  • Alternative administration strategies, such as a 3- or 4-injection double-dose vaccination series or an accelerated schedule of 0, 1, and 3 weeks, may be considered [AIDSinfo 2017]
  • Test for anti-HBs 1 to 2 months after administration of the last dose of the vaccination series [Rubin et al. 2014]
Revaccination Nonresponders to the primary HBV vaccination series (anti-HBs <10 IU/L) should receive a double-dose revaccination series; a 4-dose schedule should be considered 
Comments
  • In patients at risk for HBV infection, initial vaccination should not be deferred if CD4 count is <200 cells/mm3 [AIDSinfo 2017]
  • If an accelerated schedule is used, a fourth dose booster should be administered at least 6 months after initiation of the series; the accelerated schedule is not recommended for patients with CD4 counts ­<500 cells/mm3
  • The HAV/HBV combined vaccine is not recommended for the double-dose or 4-injection HBV vaccination strategy
  • HEPLISAV-B, a two-dose (1 month apart) recombinant HBV surface antigen vaccine with a novel adjuvant is now available. There are no data available on use among people with HIV. There were no autoimmune adverse events among people with HIV exposed to the adjuvant [FDA 2017; Schillie et al. 2018a]
  • See the NYSDOH AI guideline HBV-HIV Coinfection
  • Covered by the Vaccine Injury Compensation Program

Discussion: The HBV vaccine is recommended for all adults with HIV who do not have immunity to HBV and who do not have chronic HBV infection [CDC 2017]. The antibody response to the HBV vaccine is reduced in persons with HIV compared with those who do not have HIV; the reported immune response to the standard dose (20 µg) ranges from 34% to 89% [Mast et al. 2006; Mena et al. 2015], with diminishing response with lower CD4 cell counts [Overton et al. 2005; Kim et al. 2008; Pettit et al. 2010; Pollack et al. 2016]. Undetectable or very low viral load is associated with increased response to HBV vaccination [Overton et al. 2005; Kim et al. 2008; Mena et al. 2012]. Initial vaccination should not be deferred in patients with low CD4 cell counts; some patients with HIV and CD4 counts <200 cells/mm3 may have an immune response [Whitaker et al. 2012; AIDSinfo 2017].

Improved immune response has been reported using a four-injection double-dose (40 µg) regimen [Launay et al. 2011; Chaiklang et al. 2013]. Studies of a three-injection double-dose regimen reported increased seroconversion rates compared to standard dose only among adults with HIV with CD4 counts >350 cells/mm3 and low or undetectable HIV viral load [Fonseca et al. 2005; Potsch et al. 2012]. Accelerated schedules (0, 1, and 3 weeks) may increase adherence to the full vaccination series but are not recommended for patients with CD4 counts ­<500 cells/mm3 due to the increased likelihood of nonresponse [de Vries-Sluijs et al. 2011]. Patients with HIV should be tested for anti-HBs 1 to 2 months after completing the vaccination series [Aberg et al. 2014; AIDSinfo 2017]. Other strategies to improve immune response have demonstrated some success, including intradermal administration [Launay et al. 2011] and addition of adjuvants [Sasaki et al. 2003; Cooper et al. 2005; Overton et al. 2010], but the evidence is not sufficient to make a recommendation.

Nonresponders to primary vaccination should be revaccinated using a double-dose regimen with consideration of a four-dose schedule. Several studies have reported increased response rates from double-dose revaccination among nonresponders [Cardell et al. 2008; de Vries-Sluijs et al. 2008; Psevdos et al. 2010], although the only randomized controlled trial comparing a three-injection standard dose (20 µg) to a three-injection, double-dose (40 µg) regimen for revaccination found no difference in response rates. However, the double-dose regimen resulted in a greater and more durable immune response [Rey et al. 2015]. HBV revaccination can be deferred among nonresponders who are initiating antiretroviral therapy until CD4 counts increase to ≥200 cells/mm3 [AIDSinfo 2017]. Revaccination should not be delayed in patients who are unlikely to achieve an increased CD4 cell count. For more detailed information, see the NYSDOH AI guideline HBV-HIV Coinfection.

Three HBV vaccination formulations are available in the United States. The efficacy of these vaccines has been reported to be equivalent when used in patients who do not have HIV; however, the three formulations have not yet been established to be equally effective in patients with HIV. For persons who are susceptible to both HAV and HBV, the combined HAV/HBV vaccine can be used regardless of immune status, with three doses, administered at 0, 1, and 6 months. Because no data are available regarding double-dose or four-injection HBV vaccination with the combined HAV/HBV vaccine in the presence of HIV, the combined vaccine is not recommended for the double-dose or four-injection HBV vaccination strategy. A two-dose (1 month apart) recombinant hepatitis B surface antigen vaccine with a novel adjuvant is available. There are no data available on use in people with HIV, but seroprotective rates were superior to comparator 3-dose series among older adults and adults with diabetes [Janssen 2017]. No autoimmune adverse events were reported among people with HIV exposed to the adjuvant [FDA 2017]. The two-dose option may facilitate completion rates for the vaccination series. For more information, see the NYSDOH AI guideline HBV-HIV Coinfection > Prevention.

References

Aberg JA, Gallant JE, Ghanem KG, Emmanuel P, Zingman BS, Horberg MA. Primary care guidelines for the management of persons infected with HIV: 2013 update by the HIV medicine association of the Infectious Diseases Society of America. Clin Infect Dis 2014;58(1):e1-34. [PMID: 24235263]

AIDSinfo. Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: Recommendations from the Centers for Disease Control and Prevention, the National Insitutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. 2017 Jul 6. https://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf [accessed 2018 Mar 27]

Cardell K, Akerlind B, Sallberg M, Fryden A. Excellent response rate to a double dose of the combined hepatitis A and B vaccine in previous nonresponders to hepatitis B vaccine. J Infect Dis 2008;198(3):299-304. [PMID: 18544037]

Centers for Disease Control and Prevention (CDC). Recommended Immunization Schedules for Adults. 2017 Feb 27. https://www.cdc.gov/vaccines/schedules/hcp/adult.html [accessed 2018 Mar 27]

Chaiklang K, Wipasa J, Chaiwarith R, Praparattanapan J, Supparatpinyo K. Comparison of immunogenicity and safety of four doses and four double doses vs. standard doses of hepatitis B vaccination in HIV-infected adults: a randomized, controlled trial. PLoS One 2013;8(11):e80409. [PMID: 24265819]

Cooper CL, Davis HL, Angel JB, Morris ML, Elfer SM, Seguin I, Krieg AM, Cameron DW. CPG 7909 adjuvant improves hepatitis B virus vaccine seroprotection in antiretroviral-treated HIV-infected adults. AIDS 2005;19(14):1473-1479. [PMID: 16135900]

de Vries-Sluijs TE, Hansen BE, van Doornum GJ, Kauffmann RH, Leyten EM, Mudrikova T, Brinkman K, den Hollander JG, Kroon FP, Janssen HL, et al. A randomized controlled study of accelerated versus standard hepatitis B vaccination in HIV-positive patients. J Infect Dis 2011;203(7):984-991. [PMID: 21266513]

de Vries-Sluijs TE, Hansen BE, van Doornum GJ, Springeling T, Evertsz NM, de Man RA, van der Ende ME. A prospective open study of the efficacy of high-dose recombinant hepatitis B rechallenge vaccination in HIV-infected patients. J Infect Dis 2008;197(2):292-294. [PMID: 18177248]

Food and Drug Administration (FDA). Briefing Document. Heplisav-B (Hepatitis B Vaccine Recombinant and 1018 ISS Adjuvant). 2017 Jul 28. https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/
BloodVaccinesandOtherBiologics/VaccinesandRelatedBiologicalProductsAdvisoryCommittee/UCM568492.pdf
[accessed 2018 Mar 27]

Fonseca MO, Pang LW, de Paula Cavalheiro N, Barone AA, Heloisa Lopes M. Randomized trial of recombinant hepatitis B vaccine in HIV-infected adult patients comparing a standard dose to a double dose. Vaccine 2005;23(22):2902-2908. [PMID: 15780739]

HEPLISAV-B. Highlights of prescribing information. 2017 Nov. http://www.dynavax.com/files/7815/1026/3335/HEPLISAV-B-Package-Insert.pdf [accessed 2018 Apr 20]

Janssen R. HEPLISAV-B. Advisory Committee on Immunization Practices. 2017 Oct 25. https://stacks.cdc.gov/view/cdc/57606 [accessed 2019 Jan 2]

Kim HN, Harrington RD, Van Rompaey SE, Kitahata MM. Independent clinical predictors of impaired response to hepatitis B vaccination in HIV-infected persons. Int J STD AIDS 2008;19(9):600-604. [PMID: 18725550]

Launay O, van der Vliet D, Rosenberg AR, Michel ML, Piroth L, Rey D, Colin de Verdiere N, Slama L, Martin K, Lortholary O, et al. Safety and immunogenicity of 4 intramuscular double doses and 4 intradermal low doses vs standard hepatitis B vaccine regimen in adults with HIV-1: a randomized controlled trial. JAMA 2011;305(14):1432-1440. [PMID: 21486976]

Mast EE, Weinbaum CM, Fiore AE, Alter MJ, Bell BP, Finelli L, Rodewald LE, Douglas JM, Jr., Janssen RS, Ward JW. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) Part II: immunization of adults. MMWR Recomm Rep 2006;55(Rr-16):1-33; quiz CE31-34. [PMID: 17159833]

Mena G, Garcia-Basteiro AL, Bayas JM. Hepatitis B and A vaccination in HIV-infected adults: A review. Hum Vaccin Immunother 2015;11(11):2582-2598. [PMID: 26208678]

Mena G, Llupia A, Garcia-Basteiro AL, Diez C, Leon A, Garcia F, Bayas JM. Assessing the immunological response to hepatitis B vaccination in HIV-infected patients in clinical practice. Vaccine 2012;30(24):3703-3709. [PMID: 22446635]

Overton ET, Kang M, Peters MG, Umbleja T, Alston-Smith BL, Bastow B, Demarco-Shaw D, Koziel MJ, Mong-Kryspin L, Sprenger HL, et al. Immune response to hepatitis B vaccine in HIV-infected subjects using granulocyte-macrophage colony-stimulating factor (GM-CSF) as a vaccine adjuvant: ACTG study 5220. Vaccine 2010;28(34):5597-5604. [PMID: 20600512]

Overton ET, Sungkanuparph S, Powderly WG, Seyfried W, Groger RK, Aberg JA. Undetectable plasma HIV RNA load predicts success after hepatitis B vaccination in HIV-infected persons. Clin Infect Dis 2005;41(7):1045-1048. [PMID: 16142673]

Pettit NN, DePestel DD, Malani PN, Riddell Jt. Factors associated with seroconversion after standard dose hepatitis B vaccination and high-dose revaccination among HIV-infected patients. HIV Clin Trials 2010;11(6):332-339. [PMID: 21239361]

Pollack TM, Trang le TT, Ngo L, Cuong do D, Thuy PT, Colby DJ. Response to hepatitis B vaccination among HIV-infected adults in Vietnam. J Virus Erad 2016;2(2):102-106. [PMID: 27482443]

Potsch DV, Camacho LA, Tuboi S, Villar LM, Miguel JC, Ginuino C, Silva EF, Mendonca RM, Moreira RB, Barroso PF. Vaccination against hepatitis B with 4-double doses increases response rates and antibodies titers in HIV-infected adults. Vaccine 2012;30(41):5973-5977. [PMID: 22828589]

Psevdos G, Kim JH, Groce V, Sharp V. Efficacy of double-dose hepatitis B rescue vaccination in HIV-infected patients. AIDS Patient Care STDS 2010;24(7):403-407. [PMID: 20586648]

Rey D, Piroth L, Wendling MJ, Miailhes P, Michel ML, Dufour C, Haour G, Sogni P, Rohel A, Ajana F, et al. Safety and immunogenicity of double-dose versus standard-dose hepatitis B revaccination in non-responding adults with HIV-1 (ANRS HB04 B-BOOST): a multicentre, open-label, randomised controlled trial. Lancet Infect Dis 2015;15(11):1283-1291. [PMID: 26257021]

Rubin LG, Levin MJ, Ljungman P, Davies EG, Avery R, Tomblyn M, Bousvaros A, Dhanireddy S, Sung L, Keyserling H, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis 2014;58(3):e44-100. [PMID: 24311479]

Sasaki M, Foccacia R, de Messias-Reason IJ. Efficacy of granulocyte-macrophage colony-stimulating factor (GM-CSF) as a vaccine adjuvant for hepatitis B virus in patients with HIV infection. Vaccine 2003;21(31):4545-4549. [PMID: 14575766]

Schillie S, Harris A, Link-Gelles R, Romero J, Ward J, Nelson N. Recommendations of the Advisory Committee on Immunization Practices for Use of a Hepatitis B Vaccine with a Novel Adjuvant. MMWR Morb Mortal Wkly Rep 2018a;67(15):455-458. [PMID: 29672472]

Schillie S, Vellozzi C, Reingold A, Harris A, Haber P, Ward JW, Nelson NP. Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep 2018b;67(No. RR-1):1–31.

Whitaker JA, Rouphael NG, Edupuganti S, Lai L, Mulligan MJ. Strategies to increase responsiveness to hepatitis B vaccination in adults with HIV-1. Lancet Infect Dis 2012;12(12):966-976. [PMID: 23174382]

Human Papillomavirus (HPV)

Medical Care Criteria Committee, April 2018

Table 4: HPV Vaccine
Trade Names Gardasil 9
Indications All patients aged 9 to 26 years who were not previously vaccinated or did not receive a complete three-dose series (see CDC: Recommended Immunization Schedule for Adults Aged 19 Years or Older, United States 2018)
Administration Administer through age 26 years as a three-dose series according to the CDC Immunization Schedule for adults with immunocompromising conditions
Revaccination None 
Comments
  • A two-dose schedule is not recommended [CDC 2017a]
  • Because of the broader coverage offered by the 9-valent HPV vaccine, it is the only HPV vaccine currently available in the United States (see CDC: HPV Vaccine Information for Clinicians for more information)
  • Although the 9-valent vaccine has not been specifically studied in people with HIV, it is expected that the response will be the same in this population as with the 4-valent vaccine
  • Follow recommendations for cervical and anal cancer screening in women with HIV and men who have received the HPV vaccine [AIDSinfo 2017]
  • Covered by the Vaccine Injury Compensation Program

Discussion: The HPV vaccine is safe and immunogenic among individuals with HIV [Giacomet et al. 2014; Kojic et al. 2014; Markowitz et al. 2014; Toft et al. 2014; Faust et al. 2016] and is recommended for females and males aged 9 to 26 years if they did not already receive a complete three-dose series [CDC 2017b]. Routine HPV vaccination is recommended for all adolescents at age 11 to 12 years [CDC 2018]. Available data do not support HPV vaccination in all adults older than 26 years, including those with HIV [Wilkin et al. 2016]. Mathematical modeling based on the quadrivalent vaccine has demonstrated that offering HPV vaccination to MSM with HIV up to age 40 years likely would be cost-effective [Lin et al. 2017]; however, this study did not account for lower vaccine response rates with increased age. Other analyses demonstrate 1) efficacy in adults older than 26 years, although at rates lower than in adolescents; 2) a comparable immune response for HPV type 16; and 3) a slightly lower immune response for HPV types 6, 11, and 18 among women aged 25 to 45 years [Munoz et al. 2009; Westra et al. 2011].

The HPV vaccine is approved by the U.S. Food and Drug Administration for preventive but not therapeutic use; there are no data to support the use of the HPV vaccine to ameliorate existing disease. In individuals who have had an abnormal Pap test result before being vaccinated, the HPV vaccine may protect against infection from HPV types other than those that caused earlier or existing cervical abnormalities. HPV vaccination should be offered regardless of CD4 cell count [AIDSinfo 2017]. Lower seroconversion rates after HPV vaccination have been reported among women with HIV who are not taking antiretroviral therapy [Kahn et al. 2013] or who have CD4 counts <200 cells/mm3 and/or HIV viral load >10,000 copies/ml, compared with women who do not have HIV [Kojic et al. 2014]. In another study, women with HIV and a suppressed viral load had a 1.74 to 3.03 times higher peak antibody response than those who did not have viral suppression at the time of first injection; the clinical significance of this finding is not known [Money et al. 2016].

In individuals who have had an abnormal Pap test before being vaccinated, the HPV vaccine may protect against infection from HPV subtypes other than those that caused earlier or existing cervical abnormalities. However, the vaccine does not cover all HPV serotypes that increase risk of cancer, and the vaccine may be less effective in individuals with HIV. In women and men with HIV who have received the HPV vaccine, clinicians should continue to follow recommendations for cervical and anal cytologic screening, including visual inspection of the anogenital area during annual examinations [AIDSinfo 2017] (see the NYSDOH AI guidelines Cervical Screening for Dysplasia and Cancer and Anal Dysplasia and Cancer).

HPV testing is not required before administration of the vaccine [Markowitz et al. 2014]. The two-dose schedule is not recommended for immunocompromised adults, including those with HIV [Meites et al. 2016]. There is no recommendation for obtaining follow-up antibody titers because the minimum protective titers have not been established and the immune response rate is high [Markowitz et al. 2014]. Although the 9-valent vaccine has not been specifically studied in people with HIV, it is the preferred vaccine because of the broader range of HPV subtypes seen in this population [AIDSinfo 2017].

References

AIDSinfo. Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: Recommendations from the Centers for Disease Control and Prevention, the National Insitutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. 2017 Jul 6. https://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf [accessed 2018 Mar 27]

Centers for Disease Control and Prevention (CDC). Clinician FAQ: CDC Recommendations for HPV Vaccine 2-Dose Schedules. 2017a Nov 30. https://www.cdc.gov/hpv/downloads/hcvg15-ptt-hpv-2dose.pdf [accessed 2018 Mar 27]

Centers for Disease Control and Prevention (CDC). Recommended Immunization Schedules for Adults. 2017b Feb 27. https://www.cdc.gov/vaccines/schedules/hcp/adult.html [accessed 2018 Mar 27]

Centers for Disease Control and Prevention (CDC). Recommended Immunization Schedule for Children and Adolescents Aged 18 Years or Younger, United States, 2018. 2018 Mar 2. https://www.cdc.gov/vaccines/schedules/downloads/child/0-18yrs-child-combined-schedule.pdf [accessed 2018 Mar 27]

Faust H, Toft L, Sehr P, Muller M, Bonde J, Forslund O, Ostergaard L, Tolstrup M, Dillner J. Human Papillomavirus neutralizing and cross-reactive antibodies induced in HIV-positive subjects after vaccination with quadrivalent and bivalent HPV vaccines. Vaccine 2016;34(13):1559-1565. [PMID: 26896686]

Giacomet V, Penagini F, Trabattoni D, Vigano A, Rainone V, Bernazzani G, Bonardi CM, Clerici M, Bedogni G, Zuccotti GV. Safety and immunogenicity of a quadrivalent human papillomavirus vaccine in HIV-infected and HIV-negative adolescents and young adults. Vaccine 2014;32(43):5657-5661. [PMID: 25149430]

Kahn JA, Xu J, Kapogiannis BG, Rudy B, Gonin R, Liu N, Wilson CM, Worrell C, Squires KE. Immunogenicity and safety of the human papillomavirus 6, 11, 16, 18 vaccine in HIV-infected young women. Clin Infect Dis 2013;57(5):735-744. [PMID: 23667266]

Kojic EM, Kang M, Cespedes MS, Umbleja T, Godfrey C, Allen RT, Firnhaber C, Grinsztejn B, Palefsky JM, Webster-Cyriaque JY, et al. Immunogenicity and safety of the quadrivalent human papillomavirus vaccine in HIV-1-infected women. Clin Infect Dis 2014;59(1):127-135. [PMID: 24723284]

Lin A, Ong KJ, Hobbelen P, King E, Mesher D, Edmunds WJ, Sonnenberg P, Gilson R, Bains I, Choi YH, et al. Impact and Cost-effectiveness of Selective Human Papillomavirus Vaccination of Men Who Have Sex With Men. Clin Infect Dis 2017;64(5):580-588. [PMID: 28011615]

Markowitz LE, Dunne EF, Saraiya M, Chesson HW, Curtis CR, Gee J, Bocchini JA, Jr., Unger ER. Human papillomavirus vaccination: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2014;63(Rr-05):1-30. [PMID: 25167164]

Meites E, Kempe A, Markowitz LE. Use of a 2-Dose Schedule for Human Papillomavirus Vaccination – Updated Recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep 2016;65(49):1405-1408. [PMID: 27977643]

Money DM, Moses E, Blitz S, Vandriel SM, Lipsky N, Walmsley SL, Loutfy M, Trottier S, Smaill F, Yudin MH, et al. HIV viral suppression results in higher antibody responses in HIV-positive women vaccinated with the quadrivalent human papillomavirus vaccine. Vaccine 2016;34(40):4799-4806. [PMID: 27544584]

Munoz N, Manalastas R, Jr., Pitisuttithum P, Tresukosol D, Monsonego J, Ault K, Clavel C, Luna J, Myers E, Hood S, et al. Safety, immunogenicity, and efficacy of quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine in women aged 24-45 years: a randomised, double-blind trial. Lancet 2009;373(9679):1949-1957. [PMID: 19493565]

Toft L, Storgaard M, Muller M, Sehr P, Bonde J, Tolstrup M, Ostergaard L, Sogaard OS. Comparison of the immunogenicity and reactogenicity of Cervarix and Gardasil human papillomavirus vaccines in HIV-infected adults: a randomized, double-blind clinical trial. J Infect Dis 2014;209(8):1165-1173. [PMID: 24273179]

Westra TA, Rozenbaum MH, Rogoza RM, Nijman HW, Daemen T, Postma MJ, Wilschut JC. Until which age should women be vaccinated against HPV infection? Recommendation based on cost-effectiveness analyses. J Infect Dis 2011;204(3):377-384. [PMID: 21742836]

Wilkin TJ, Chen H, Cespedes M, Paczuski P, Godfrey C, Chiao E, Luque A, Webster-Cyriaque JY, Bastow B, Cranston R. ACTG A5298: A Phase 3 Trial of the Quadrivalent HPV Vaccine in Older HIV+ Adults. CROI; 2016 Feb 22-25; Boston, MA. http://www.croiconference.org/sessions/actg-a5298-phase-3-trial-quadrivalent-hpv-vaccine-older-hiv-adults

Influenza

Medical Care Criteria Committee, April 2018

Table 5: Influenza Vaccine
Trade Names See the CDC’s annual seasonal influenza vaccines table
Indications For all patients, as determined by the CDC’s Recommended Immunization Schedule for Adults Aged 19 Years or Older, United States 2018 
Administration Administer annually during flu season (October through May) according to 

the CDC’s Immunization Schedule

Revaccination None
Comments Covered by the Vaccine Injury Compensation Program

Discussion: People with HIV are at greater risk of severe morbidity from an influenza infection [Kunisaki and Janoff 2009; ACIP 2013] than people who do not have HIV and should be vaccinated annually during flu season (October through May) according to standard (CDC) guidelines for all adults [ACIP 2013; Aberg et al. 2014]. Inactivated influenza vaccine offers protective immunity in adults with HIV [Beck et al. 2012; ACIP 2013; Remschmidt et al. 2014]. Live attenuated influenza vaccine should not be used for individuals with HIV. Antibody titers lower than those observed in the general population have been reported among adults with HIV, especially among those with advanced HIV disease who are older than 35 years, have low CD4 cell counts, and have detectable viremia [Kroon et al. 2000; Yamanaka et al. 2005; Evison et al. 2009; Crum-Cianflone et al. 2011; Garg et al. 2016]. Studies comparing intradermal and intramuscular vaccines report no difference in immunogenicity, but intradermal vaccination is associated with increased likelihood of redness, swelling, and tenderness at the injection site [Garg et al. 2016; Seo et al. 2016].

The CDC does not recommend a second vaccination in individuals with HIV [ACIP 2013], although one study reported that a second dose of an adjuvanted vaccine significantly increased the rate of seroprotective responses [Bickel et al. 2011]. There is some evidence that influenza seroprotection is higher for people aged 18 years or older who are given a double-dose vaccine than for those given the standard dose vaccine, but the clinical significance of this remains unknown [Cooper et al. 2011; McKittrick et al. 2013]. Another study among children and young adults (3 to 21 years of age) found no increased immunity among participants with HIV who received the double-dose vaccine [Hakim et al. 2016]. The high-dose vaccine is not licensed for people younger than 65 years.

Results of two studies suggest a possible benefit to delaying influenza vaccination to after mid-November; patients vaccinated later in the flu season had lower rates of laboratory-confirmed influenza and influenza-like illnesses than those vaccinated earlier in the season [Werker et al. 2014; Glinka et al. 2016]. Monitoring regional influenza activity will help ensure appropriate timing of influenza vaccination. There is no recommendation for post-vaccination serologic testing to determine immune response [ACIP 2013].

References

Aberg JA, Gallant JE, Ghanem KG, Emmanuel P, Zingman BS, Horberg MA. Primary care guidelines for the management of persons infected with HIV: 2013 update by the HIV medicine association of the Infectious Diseases Society of America. Clin Infect Dis 2014;58(1):e1-34. [PMID: 24235263]

Advisory Committee on Immunization Practices (ACIP). Prevention and control of seasonal influenza with vaccines. Recommendations of the Advisory Committee on Immunization Practices–United States, 2013-2014. MMWR Recomm Rep 2013;62(Rr-07):1-43. [PMID: 24048214]

Beck CR, McKenzie BC, Hashim AB, Harris RC, Nguyen-Van-Tam JS. Influenza vaccination for immunocompromised patients: systematic review and meta-analysis by etiology. J Infect Dis 2012;206(8):1250-1259. [PMID: 22904335]

Bickel M, von Hentig N, Wieters I, Khaykin P, Nisius G, Haberl A, Stephan C, Herrmann E, Doerr HW, Brodt HR, et al. Immune response after two doses of the novel split virion, adjuvanted pandemic H1N1 influenza A vaccine in HIV-1-infected patients. Clin Infect Dis 2011;52(1):122-127. [PMID: 21148530]

Cooper C, Thorne A, Klein M, Conway B, Boivin G, Haase D, Shafran S, Zubyk W, Singer J, Halperin S, et al. Immunogenicity is not improved by increased antigen dose or booster dosing of seasonal influenza vaccine in a randomized trial of HIV infected adults. PLoS One 2011;6(3):e17758. [PMID: 21512577]

Crum-Cianflone NF, Eberly LE, Duplessis C, Maguire J, Ganesan A, Faix D, Defang G, Bai Y, Iverson E, Lalani T, et al. Immunogenicity of a monovalent 2009 influenza A (H1N1) vaccine in an immunocompromised population: a prospective study comparing HIV-infected adults with HIV-uninfected adults. Clin Infect Dis 2011;52(1):138-146. [PMID: 21148532]

Evison J, Farese S, Seitz M, Uehlinger DE, Furrer H, Muhlemann K. Randomized, double-blind comparative trial of subunit and virosomal influenza vaccines for immunocompromised patients. Clin Infect Dis 2009;48(10):1402-1412. [PMID: 19361304]

Garg S, Thongcharoen P, Praphasiri P, Chitwarakorn A, Sathirapanya P, Fernandez S, Rungrojcharoenkit K, Chonwattana W, Mock PA, Sukwicha W, et al. Randomized Controlled Trial to Compare Immunogenicity of Standard-Dose Intramuscular Versus Intradermal Trivalent Inactivated Influenza Vaccine in HIV-Infected Men Who Have Sex With Men in Bangkok, Thailand. Clin Infect Dis 2016;62(3):383-391. [PMID: 26486702]

Glinka ER, Smith DM, Johns ST. Timing Matters – Influenza Vaccination to HIV-Infected Patients. HIV Med 2016;17(8):601-604. [PMID: 26810556]

Hakim H, Allison KJ, Van de Velde LA, Tang L, Sun Y, Flynn PM, McCullers JA. Immunogenicity and safety of high-dose trivalent inactivated influenza vaccine compared to standard-dose vaccine in children and young adults with cancer or HIV infection. Vaccine 2016;34(27):3141-3148. [PMID: 27129426]

Kroon FP, van Dissel JT, de Jong JC, Zwinderman K, van Furth R. Antibody response after influenza vaccination in HIV-infected individuals: a consecutive 3-year study. Vaccine 2000;18(26):3040-3049. [PMID: 10825608]

Kunisaki KM, Janoff EN. Influenza in immunosuppressed populations: a review of infection frequency, morbidity, mortality, and vaccine responses. Lancet Infect Dis 2009;9(8):493-504. [PMID: 19628174]

McKittrick N, Frank I, Jacobson JM, White CJ, Kim D, Kappes R, DiGiorgio C, Kenney T, Boyer J, Tebas P. Improved immunogenicity with high-dose seasonal influenza vaccine in HIV-infected persons: a single-center, parallel, randomized trial. Ann Intern Med 2013;158(1):19-26. [PMID: 23277897]

Remschmidt C, Wichmann O, Harder T. Influenza vaccination in HIV-infected individuals: systematic review and assessment of quality of evidence related to vaccine efficacy, effectiveness and safety. Vaccine 2014;32(43):5585-5592. [PMID: 25131742]

Seo YB, Lee J, Song JY, Choi HJ, Cheong HJ, Kim WJ. Safety and immunogenicity of influenza vaccine among HIV-infected adults: Conventional vaccine vs. intradermal vaccine. Hum Vaccin Immunother 2016;12(2):478-484. [PMID: 26431466]

Werker GR, Sharif B, Sun H, Cooper C, Bansback N, Anis AH. Optimal timing of influenza vaccination in patients with human immunodeficiency virus: a Markov cohort model based on serial study participant hemoagglutination inhibition titers. Vaccine 2014;32(6):677-684. [PMID: 24355089]

Yamanaka H, Teruya K, Tanaka M, Kikuchi Y, Takahashi T, Kimura S, Oka S. Efficacy and immunologic responses to influenza vaccine in HIV-1-infected patients. J Acquir Immune Defic Syndr 2005;39(2):167-173. [PMID: 15905732]

Measles, Mumps, Rubella (MMR)

Medical Care Criteria Committee, April 2018

Table 6: MMR Vaccine
Trade Names
  • M-M-R II
  • MMR + varicella: ProQuad 
Indications For patients with CD4 counts ≥200 cells/mm3 who do not have evidence of MMR immunity, as determined by the CDC’s Recommended Immunization Schedule for Adults Aged 19 Years or Older, United States 2018 
Administration Two doses at least 28 days apart (see the CDC Immunization Schedule)
Revaccination Recommended only in the setting of an outbreak (see the CDC Immunization Schedule)
Comments
  • Contraindicated for patients with CD4 counts <200 cells/mm3 (see the CDC Immunization Schedule)
  • MMR + varicella (MMRV) should not be substituted for MMR [McLean et al. 2013; Rubin et al. 2014]
  • Those who previously received two doses of a mumps-containing vaccine and are at increased risk for mumps in the setting of an outbreak should receive a third dose to improve protection against mumps disease and related complications [Marin et al. 2018]
  • Covered by the Vaccine Injury Compensation Program

Discussion: Immunocompromised persons are at increased risk of serious and life-threatening complications if infected with measles [McLean et al. 2013]. Patients with HIV who have CD4 counts >200 cells/mm3 and who do not have evidence of immunity to MMR should be vaccinated with two doses of MMR vaccine at least 28 days apart. Documentation of previous age-appropriate vaccination or laboratory confirmation of prior disease is acceptable evidence of immunity. Serologic screening is required if other acceptable evidence of immunity is not available and to determine rubella immunity among individuals of childbearing potential. In the absence of other evidence of immunity, persons with perinatally acquired HIV who received childhood vaccination with MMR before establishment of effective ART should be revaccinated (two doses) after effective antiretroviral therapy (ART) is established [McLean et al. 2013]. There is no recommendation for post-vaccination serologic testing to determine immune response [McLean et al. 2013].

Two studies that examined the antibody response after MMR vaccination in adults with HIV taking ART reported high levels of protective antibodies post-vaccination, although the levels were lower than in adults without HIV. A study conducted in Mexico among adults with HIV who were seronegative for measles reported no significant difference in initial antibody response to measles vaccination between adults with and without HIV (81% vs 85%). However, at 1 year, the observed decline in antibody response was faster in adults with HIV than in those without [Belaunzaran-Zamudio et al. 2009]. A recent study in Thailand reported protective antibodies to measles (74.1%), mumps (65.7%), and rubella (93.3%) among adults with HIV 8 to 12 weeks after vaccination with MMR. Compared with adults without HIV, the seroconversion rates were lower but reached statistical significance only for mumps [Chaiwarith et al. 2016].

No data are available on revaccination in adults with HIV. Revaccination has improved measles antibody response in children with HIV on ART who had an inadequate initial response to vaccination [Aurpibul et al. 2007; Abzug et al. 2012]. If persons previously vaccinated with two doses of a mumps-containing vaccine are identified as at increased risk for mumps by public health authorities because of an outbreak, these at-risk individuals should receive a third dose of a mumps-containing vaccine to improve protection against mumps disease and related complications [Marin et al. 2018].

MMR vaccination contains live virus and is contraindicated for patients with CD4 counts <200 cells/mm3 due to reports of adverse events, such as measles pneumonitis, in severely compromised patients [CDC 1996; Angel et al. 1998]. Serious adverse effects have not been reported in adults who were not severely immunocompromised [Belaunzaran-Zamudio et al. 2009; McLean et al. 2013; Chaiwarith et al. 2016]. MMRV has not been adequately studied in individuals with HIV and is not recommended as a substitute for MMR in this population [McLean et al. 2013; Rubin et al. 2014].

References

Abzug MJ, Qin M, Levin MJ, Fenton T, Beeler JA, Bellini WJ, Audet S, Sowers SB, Borkowsky W, Nachman SA, et al. Immunogenicity, immunologic memory, and safety following measles revaccination in HIV-infected children receiving highly active antiretroviral therapy. J Infect Dis 2012;206(4):512-522. [PMID: 22693229]

Angel JB, Walpita P, Lerch RA, Sidhu MS, Masurekar M, DeLellis RA, Noble JT, Snydman DR, Udem SA. Vaccine-associated measles pneumonitis in an adult with AIDS. Ann Intern Med 1998;129(2):104-106. [PMID: 9669968]

Aurpibul L, Puthanakit T, Sirisanthana T, Sirisanthana V. Response to measles, mumps, and rubella revaccination in HIV-infected children with immune recovery after highly active antiretroviral therapy. Clin Infect Dis 2007;45(5):637-642. [PMID: 17683001]

Belaunzaran-Zamudio PF, Garcia-Leon ML, Wong-Chew RM, Villasis-Keever A, Cuellar-Rodriguez J, Mosqueda-Gomez JL, Munoz-Trejo T, Escobedo K, Santos JI, Ruiz-Palacios GM, et al. Early loss of measles antibodies after MMR vaccine among HIV-infected adults receiving HAART. Vaccine 2009;27(50):7059-7064. [PMID: 19799846]

Centers for Disease Control and Prevention (CDC). Measles pneumonitis following measles-mumps-rubella vaccination of a patient with HIV infection, 1993. MMWR Morb Mortal Wkly Rep 1996;45(28):603-606. [PMID: 8676852]

Chaiwarith R, Praparattanapan J, Nuket K, Kotarathitithum W, Supparatpinyo K. Seroprevalence of antibodies to measles, mumps, and rubella, and serologic responses after vaccination among human immunodeficiency virus (HIV)-1 infected adults in Northern Thailand. BMC Infect Dis 2016;16:190. [PMID: 27138005]

Marin M, Marlow M, Moore KL, Patel M. Recommendation of the Advisory Committee on Immunization Practices for Use of a Third Dose of Mumps Virus-Containing Vaccine in Persons at Increased Risk for Mumps During an Outbreak. MMWR Morb Mortal Wkly Rep 2018;67(1):33-38. [PMID: 29324728]

McLean HQ, Fiebelkorn AP, Temte JL, Wallace GS. Prevention of measles, rubella, congenital rubella syndrome, and mumps, 2013: summary recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2013;62(Rr-04):1-34. [PMID: 23760231]

Rubin LG, Levin MJ, Ljungman P, Davies EG, Avery R, Tomblyn M, Bousvaros A, Dhanireddy S, Sung L, Keyserling H, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis 2014;58(3):e44-100. [PMID: 24311479]

Meningococcal Serotype Non-B (MenACWY)

Medical Care Criteria Committee, April 2018

Table 7: MenACWY Vaccine
Trade Names
  • MenACWY: Menactra
  • MCV4: Menveo
Indications
Administration
  • Administer two doses of MenACWY at least 8 weeks apart in those not previously vaccinated (see the CDC Immunization Schedule)
  • For those previously vaccinated with one dose of MenACWY, administer the second dose at the earliest opportunity at least 8 weeks after the previous dose (see the CDC Immunization Schedule)
Revaccination Administer one booster dose of MenACWY every 5 years (see the CDC Immunization Schedule)
Comments

Discussion: Adults with HIV are at increased risk of invasive meningococcal disease due to serogroups C, W, and Y. [MacNeil et al. 2016; Folaranmi et al. 2017]. A recent study in New York City reported a 10-fold increased risk of invasive meningococcal disease in patients with HIV, with the highest risk among those with CD4 counts <200 cells/mm3 [Miller et al. 2014]. As of 2017, the CDC recommends vaccinating all previously unvaccinated adults with HIV with a two-dose primary series of MenACWY (MenACWY-CRM or MenACWY-D) administered at least 8 weeks apart [MacNeil et al. 2016].

Data on meningococcal vaccine efficacy among adults with HIV are not currently available [MacNeil et al. 2016]. Among adolescents with HIV, available evidence indicates that the vaccine is immunogenic and serious adverse events are rare, but adolescents with HIV (and especially those with lower CD4 cell counts and higher viral loads) had reduced antibody levels compared with adolescents without HIV [Siberry et al. 2010; Lujan-Zilbermann et al. 2012]. Adding a second vaccine dose significantly improved antibody levels 28 and 72 weeks after immunization, particularly among adolescents with CD4% >15 [Lujan-Zilbermann et al. 2012].

Booster doses every 5 years are needed to maintain immunity. Although MPSV4 is the only meningococcal vaccine licensed for persons aged 56 years or older, MenACWY is preferred among older adults because of the need for revaccination. Limited data among healthy adults suggest a greater immune response after a booster dose of MenACWY than with MPSV4; however, no data are available for adults with HIV. There is no recommendation for post-vaccination serologic testing to determine immune response [MacNeil et al. 2016].

References

Folaranmi TA, Kretz CB, Kamiya H, MacNeil JR, Whaley MJ, Blain A, Antwi M, Dorsinville M, Pacilli M, Smith S, et al. Increased Risk for Meningococcal Disease among Men who have Sex with Men in the United States, 2012-2015. Clin Infect Dis 2017. [PMID: 28505234]

Lujan-Zilbermann J, Warshaw MG, Williams PL, Spector SA, Decker MD, Abzug MJ, Heckman B, Manzella A, Kabat B, Jean-Philippe P, et al. Immunogenicity and safety of 1 vs 2 doses of quadrivalent meningococcal conjugate vaccine in youth infected with human immunodeficiency virus. J Pediatr 2012;161(4):676-681.e672. [PMID: 22622049]

MacNeil JR, Rubin LG, Patton M, Ortega-Sanchez IR, Martin SW. Recommendations for Use of Meningococcal Conjugate Vaccines in HIV-Infected Persons – Advisory Committee on Immunization Practices, 2016. MMWR Morb Mortal Wkly Rep 2016;65(43):1189-1194. [PMID: 27811836]

Miller L, Arakaki L, Ramautar A, Bodach S, Braunstein SL, Kennedy J, Steiner-Sichel L, Ngai S, Shepard C, Weiss D. Elevated risk for invasive meningococcal disease among persons with HIV. Ann Intern Med 2014;160(1):30-37. [PMID: 24166695]

Siberry GK, Williams PL, Lujan-Zilbermann J, Warshaw MG, Spector SA, Decker MD, Heckman BE, Demske EF, Read JS, Jean-Philippe P, et al. Phase I/II, open-label trial of safety and immunogenicity of meningococcal (groups A, C, Y, and W-135) polysaccharide diphtheria toxoid conjugate vaccine in human immunodeficiency virus-infected adolescents. Pediatr Infect Dis J 2010;29(5):391-396. [PMID: 20431379]

Meningococcal Serotype B (MenB)

Medical Care Criteria Committee, April 2018

Table 8: MenB Vaccine
Trade Names Bexsero; Trumenba
Indications Patients at risk of MenB infection, as determined by the CDC’s Recommended Immunization Schedule for Adults Aged 19 Years or Older, United States 2018 
Administration Administer according to the CDC Immunization Schedule for patients at risk
Revaccination None
Comments

Discussion: MenB vaccine is not routinely recommended for adults with HIV unless they have another indication for immunization. No increased risk of serogroup B meningococcal disease among individuals with HIV has been reported [CDC 2017].

Reference

Centers for Disease Control and Prevention (CDC). Recommended Immunization Schedules for Adults. 2017 Feb 27. https://www.cdc.gov/vaccines/schedules/hcp/adult.html [accessed 2018 Mar 27]

Pneumococcal

Medical Care Criteria Committee, April 2018

Table 9: Pneumococcal Vaccine: 13-Valent and 23-Valent (PCV13, PPSV23)
Trade Names Prevnar 13 (PCV130); Pneumovax 23 (PPSV23)
Indications All patients with HIV (see the CDC’s Recommended Immunization Schedule for Adults Aged 19 Years or Older, United States 2018)
Administration
  • The complete series of vaccinations is one dose of PCV13 and two doses of PPSV23 before age 65 years, followed by one additional dose of PPSV23 after age 65 years (see the CDC Immunization Schedule)
  • See Table 10, below, for detailed administration guidelines based on age and previous vaccination history
Revaccination See Table 10, below
Comments The PCV13 vaccine should be not be deferred for patients with CD4 count <200 cells mm3 and/or detectable viral load; however, the follow-up secondary administration of PPSV23 vaccine may be deferred until the patient’s CD4 count is >200 cells mm3 and/or viral load is undetectable 

Discussion: Individuals with HIV are at increased risk of serious disease due to Streptococcus pneumoniae, including bacteremia, meningitis, and pneumonia. Pneumococcal vaccination is recommended for all adults with HIV as soon as possible after HIV diagnosis [CDC 2012, 2017]. The complete series is one dose of PCV13 as a priming vaccine, followed by two doses of PPSV23 before age 65 years, and one additional dose of PPSV23 after age 65 years. Because only one dose of PPSV23 is recommended after a patient reaches age 65 years, those who begin vaccination at age 65 years or older should receive one dose of PCV13 and one dose of PPSV23 [Tomczyk et al. 2014]. There is no recommendation for post-vaccination serologic testing to determine immune response [CDC 2012, 2017]. See Table 10 for vaccination recommendations by previous pneumococcal immunization history and age at time of initial evaluation.

Pneumococcal vaccination has been demonstrated to reduce pneumococcal bacteremia and mortality among adults with HIV [Hung et al. 2004; Grau et al. 2005; Rodriguez-Barradas et al. 2008; Chowers et al. 2017]. Both polysaccharide and conjugate pneumococcal vaccines appear to be safe and immunogenic among adults with HIV who have CD4 counts >200 cells/mm3 [Ho et al. 2013; Bhorat et al. 2015; Rodriguez-Barradas et al. 2015; Lombardi et al. 2016]. In a recent randomized controlled trial, the prime-boost regimen of PCV13 followed by PPSV23 significantly increased antibody response compared with PPSV23 alone in adults with HIV [Sadlier et al. 2016].

Patients with CD4 counts <200 cells/mm3 are at the highest risk of pneumococcal disease. Because immunogenicity has been demonstrated for individuals with HIV with CD4 counts <200 cells/mm3 who received PCV7 [French et al. 2010], use of PCV13 may be considered in severely immunocompromised patients. Patients with HIV who have not previously received any pneumococcal vaccine should receive a dose of PCV13, regardless of CD4 cell count. Although there is evidence of the effectiveness of PPSV23 among patients with CD4 counts <200 cells/mm3, the benefit appears to be greatest among patients with viral loads <100,000 copies/mL and among those who are on antiretroviral therapy.

If zoster vaccine is also being administered, it should be separated from the pneumococcal vaccine by at least 4 weeks [Zostavax 2017].

Table 10. Pneumococcal Vaccination Recommendations for Adults with HIV, by Previous Pneumococcal Immunization History and Age at Time of Initial Evaluation (see CDC Immunization Schedule)
Previous Immunization History Aged 18-64 Years Aged 65 Years or Older

No previous PCV13/PPSV23* or unknown status

*by clinical documentation or patient self-report

  • 1 dose of PCV13, then
  • 1st dose of PPSV23 ≥8 weeks later, then
  • 2nd dose of PPSV23 ≥5 years after 1st dose of PPSV23, then
  • 3rd dose of PPSV23 if 65 years or older and ≥5 years since 2nd dose of PPSV23 and 2nd dose of PPSV23 given before age 65 years
  • 1 dose of PCV13, then
  • 1 dose of PPSV23 ≥8 weeks later

No PCV13

+

1 dose of PPSV23

  • 1 dose of PCV13 ≥1 year after 1st dose of PPSV23, then
  • 2nd dose of PPSV23 if both ≥8 weeks after PCV13 dose and ≥5 years after 1st dose of PPSV23, then
  • 3rd dose of PPSV23 if 65 years or older and ≥5 years since 2nd dose of PPSV23 and 2nd dose of PPSV23 given before age 65 years
  • 1 dose of PCV13 ≥1 year after 1st dose of PPSV23, then
  • 2nd dose of PPSV23 if both ≥8 weeks after PCV13 dose and ≥5 years after 1st dose of PPSV23 and 1st dose of PPSV23 was given before age 65 years

No PCV13

+

2 doses of PPSV23

  • 1 dose of PCV13 ≥1 year after most recent dose of PPSV23 and
  • 3rd dose of PPSV23 if 65 years or older and ≥5 years after 2nd dose of PPSV23 and 2nd dose of PPSV23 given before age 65 years and ≥8 weeks after PCV13 dose
  • 1 dose of PCV13 ≥1 year after most recent dose of PPSV23, then
  • 3rd dose of PPSV23 if ≥5 years after 2nd dose of PPSV23 and 2nd dose of PPSV23 given before age 65 years and ≥8 weeks after PCV13 dose 

1 dose of PCV13

+

No PPSV23

  • 1st dose of PPSV23 ≥8 weeks after PCV13 dose, then
  • 2nd dose of PPSV23 ≥5 years later, then
  • 3rd dose of PPSV23 if 65 years or older and ≥5 years since 2nd dose of PPSV23 and 2nd dose of PPSV23 given before age 65 years
  • 1 dose of PPSV23 ≥8 weeks after PCV13 dose

1 dose of PCV13

+

1 dose of PPSV23

  • 2nd dose of PPSV23 if ≥8 weeks after PCV13 dose and ≥5 years since 1st dose of PPSV23, then
  • 3rd dose of PPSV23 if both 65 years or older and ≥5 years since 2nd dose of PPSV23 and 2nd dose of PPSV23 given before age 65 years
  • If 1st dose of PPSV23 given before age 65 years: 2nd dose of PPSV23 ≥8 weeks after PCV13 dose and ≥5 years after 1st dose of PPSV23
  • If 1st dose of PPSV23 given at 65 years or older: No further doses of PPSV23 required

1 dose of PCV13

+

2 doses of PPSV23

  • If 2nd dose of PPSV23 given before age 65 years: 3rd dose of PPSV23 if 65 years or older and ≥5 years since 2nd dose of PPSV23
  • If 2nd dose of PPSV23 given before age 65 years: 3rd dose of PPSV23 ≥8 weeks after PCV13 dose and ≥5 years since 2nd dose of PPSV23
  • If 2nd dose of PPSV23 given at 65 years or older: No 3rd dose of PPSV23 required
References

Bhorat AE, Madhi SA, Laudat F, Sundaraiyer V, Gurtman A, Jansen KU, Scott DA, Emini EA, Gruber WC, Schmoele-Thoma B. Immunogenicity and safety of the 13-valent pneumococcal conjugate vaccine in HIV-infected individuals naive to pneumococcal vaccination. AIDS 2015;29(11):1345-1354. [PMID: 25888646]

Centers for Disease Control and Prevention (CDC). Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine for adults with immunocompromising conditions: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 2012;61(40):816-819. [PMID: 23051612]

Centers for Disease Control and Prevention (CDC). Recommended Immunization Schedules for Adults. 2017 Feb 27. https://www.cdc.gov/vaccines/schedules/hcp/adult.html [accessed 2018 Mar 27]

Chowers M, Regev-Yochay G, Mor O, Cohen-Poradosu R, Riesenberg K, Zimhony O, Chemtob D, Stein M, Dagan R, Levy I. Invasive pneumococcal disease (IPD) in HIV infected patients in Israel since the introduction of pneumococcal conjugated vaccines (PCV): Analysis of a nationwide surveillance study, 2009-2014. Hum Vaccin Immunother 2017;13(1):216-219. [PMID: 27648488]

French N, Gordon SB, Mwalukomo T, White SA, Mwafulirwa G, Longwe H, Mwaiponya M, Zijlstra EE, Molyneux ME, Gilks CF. A trial of a 7-valent pneumococcal conjugate vaccine in HIV-infected adults. N Engl J Med 2010;362(9):812-822. [PMID: 20200385]

Grau I, Pallares R, Tubau F, Schulze MH, Llopis F, Podzamczer D, Linares J, Gudiol F. Epidemiologic changes in bacteremic pneumococcal disease in patients with human immunodeficiency virus in the era of highly active antiretroviral therapy. Arch Intern Med 2005;165(13):1533-1540. [PMID: 16009870]

Ho YL, Brandao AP, de Cunto Brandileone MC, Lopes MH. Immunogenicity and safety of pneumococcal conjugate polysaccharide and free polysaccharide vaccines alone or combined in HIV-infected adults in Brazil. Vaccine 2013;31(37):4047-4053. [PMID: 23684823]

Hung CC, Chen MY, Hsieh SM, Hsiao CF, Sheng WH, Chang SC. Clinical experience of the 23-valent capsular polysaccharide pneumococcal vaccination in HIV-1-infected patients receiving highly active antiretroviral therapy: a prospective observational study. Vaccine 2004;22(15-16):2006-2012. [PMID: 15121313]

Lombardi F, Belmonti S, Fabbiani M, Morandi M, Rossetti B, Tordini G, Cauda R, De Luca A, Di Giambenedetto S, Montagnani F. Immunogenicity and Safety of the 13-Valent Pneumococcal Conjugate Vaccine versus the 23-Valent Polysaccharide Vaccine in Unvaccinated HIV-Infected Adults: A Pilot, Prospective Controlled Study. PLoS One 2016;11(6):e0156523. [PMID: 27258647]

Rodriguez-Barradas MC, Goulet J, Brown S, Goetz MB, Rimland D, Simberkoff MS, Crothers K, Justice AC. Impact of pneumococcal vaccination on the incidence of pneumonia by HIV infection status among patients enrolled in the Veterans Aging Cohort 5-Site Study. Clin Infect Dis 2008;46(7):1093-1100. [PMID: 18444830]

Rodriguez-Barradas MC, Serpa JA, Munjal I, Mendoza D, Rueda AM, Mushtaq M, Pirofski LA. Quantitative and Qualitative Antibody Responses to Immunization With the Pneumococcal Polysaccharide Vaccine in HIV-Infected Patients After Initiation of Antiretroviral Treatment: Results From a Randomized Clinical Trial. J Infect Dis 2015;211(11):1703-1711. [PMID: 25538270]

Sadlier C, O’Dea S, Bennett K, Dunne J, Conlon N, Bergin C. Immunological efficacy of pneumococcal vaccine strategies in HIV-infected adults: a randomized clinical trial. Sci Rep 2016;6:32076. [PMID: 27580688]

Tomczyk S, Bennett NM, Stoecker C, Gierke R, Moore MR, Whitney CG, Hadler S, Pilishvili T. Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine among adults aged >/=65 years: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 2014;63(37):822-825. [PMID: 25233284]

Zostavax. Package insert. 2017 Aug. https://www.merck.com/product/usa/pi_circulars/z/zostavax/zostavax_pi2.pdf [accessed 2018 Mar 27]

Tetanus, Diphtheria, and Pertussis (Tdap) and Tetanus-Diphtheria (Td)

Medical Care Criteria Committee, April 2018

Table 11: Tdap and Td Vaccines
Trade Names
  • Tdap: Adacel; Boostrix
  • Td: Tenivac; Decavac (generic 9Td)
Indications For all patients, as determined by the CDC’s Recommended Immunization Schedule for Adults Aged 19 Years or Older, United States 2018 for all adults
Administration Administer according to the CDC Immunization Schedule for all adults
Revaccination None
Comments Covered by the Vaccine Injury Compensation Program

Discussion: The recommendations for Tdap and Td vaccination of adults with HIV are the same as for all adults [CDC 2017]. The safety and efficacy of vaccination with Tdap has not been studied in this population [Rubin et al. 2014].

References

Centers for Disease Control and Prevention (CDC). Recommended Immunization Schedules for Adults. 2017 Feb 27. https://www.cdc.gov/vaccines/schedules/hcp/adult.html [accessed 2018 Mar 27]

Rubin LG, Levin MJ, Ljungman P, Davies EG, Avery R, Tomblyn M, Bousvaros A, Dhanireddy S, Sung L, Keyserling H, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis 2014;58(3):e44-100. [PMID: 24311479]

Varicella

Medical Care Criteria Committee, April 2018

Table 12: Varicella Vaccine
Trade Names
  • Varicella: Varivax
  • Measles, mumps, and rubella (MMR) + varicella (MMRV): ProQuad
Indications For patients with CD4 counts ≥200 cells/mm3 who do not have evidence of immunity to varicella, as determined by the CDC’s Recommended Immunization Schedule for Adults Aged 19 Years or Older, United States 2018 
Administration Administer according to the CDC Immunization Schedule for all adults
Revaccination None
Comments
  • Contraindicated for patients with CD4 counts <200 cells/mm3 (see the CDC Immunization Schedule)
  • Anti-varicella IgG screening should be performed in patients with no known history of chickenpox or shingles [Marin et al. 2007]
  • MMRV should not be used [Rubin et al. 2014]
  • Antiherpetic agents should be avoided at least 24 hours before and 14 days after administration [ACIP 2011]
  • An interval of at least 5 months is recommended between administration of post-exposure varicella IgG (VariZIG) and varicella vaccination [Cohn et al. 2013]
  • Clinical disease due to varicella after vaccination, a very rare event, should be treated with acyclovir [AIDSinfo 2017]
  • Covered by the Vaccine Injury Compensation Program

Discussion: Patients with HIV who have CD4 counts >200 cells/mm3 and do not have immunity to varicella should be vaccinated according to CDC Immunization Schedule for all adults with two doses of single-antigen varicella vaccine 4 to 8 weeks apart, or a second dose if they have received only one dose. Varicella vaccination contains live virus and is contraindicated for patients with CD4 counts <200 cells/mm3 because of the risk of disseminated disease [Kramer et al. 2001; Marin et al. 2007; CDC 2017]. Data on the effectiveness of varicella vaccination among adults with HIV are lacking, but vaccination has been shown to be effective among children with HIV [Marin et al. 2007; CDC 2012; Crum-Cianflone and Wallace 2014].

Clinicians should verify varicella immunity due to the possibility of severe disease in individuals with HIV. Birth before 1980 is not accepted as evidence of immunity in immunocompromised persons; anti-varicella IgG screening should be performed in patients with HIV who have no known history of chickenpox or shingles [Marin et al. 2007]. Post-vaccination serologic testing to determine immune response is not recommended because commercially available assays lack sensitivity and may give false-negative results [Marin et al. 2007]. Clinical disease due to varicella after vaccination, a very rare event, should be treated with acyclovir [Marin et al. 2007; AIDSinfo 2017]. If household members or close contacts develop a rash after vaccination, individuals with HIV should avoid contact with the affected person until after the rash resolves [Marin et al. 2007; ACIP 2011; Rubin et al. 2014]. Because they can interfere with vaccine virus replication and decrease vaccine effectiveness, all antiherpetic agents should be avoided for at least 72 hours before varicella vaccination through 14 days after [CDC 2016]. If post-exposure varicella immune globulin is given, clinicians should wait at least 5 months before vaccination [ACIP 2011].

References

Advisory Committee on Immunization Practices (ACIP). General recommendations on immunization — recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2011;60(2):1-64. [PMID: 21293327]

AIDSinfo. Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: Recommendations from the Centers for Disease Control and Prevention, the National Insitutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. 2017 Jul 6. https://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf [accessed 2018 Mar 27]

Centers for Disease Control and Prevention (CDC). FDA approval of an extended period for administering VariZIG for postexposure prophylaxis of varicella. MMWR Morb Mortal Wkly Rep 2012;61(12):212. [PMID: 22456121]

Centers for Disease Control and Prevention (CDC). Varicella. Epidemiology and Prevention of Vaccine-Preventable Diseases. 2016 Dec 30. https://www.cdc.gov/vaccines/pubs/pinkbook/index.html [accessed 2018 Mar 27]

Centers for Disease Control and Prevention (CDC). Recommended Immunization Schedules for Adults. 2017 Feb 27. https://www.cdc.gov/vaccines/schedules/hcp/adult.html [accessed 2018 Mar 27]

Cohn AC, MacNeil JR, Clark TA, Ortega-Sanchez IR, Briere EZ, Meissner HC, Baker CJ, Messonnier NE. Prevention and control of meningococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2013;62(Rr-2):1-28. [PMID: 23515099]

Crum-Cianflone NF, Wallace MR. Vaccination in HIV-infected adults. AIDS Patient Care STDS 2014;28(8):397-410. [PMID: 25029589]

Kramer JM, LaRussa P, Tsai WC, Carney P, Leber SM, Gahagan S, Steinberg S, Blackwood RA. Disseminated vaccine strain varicella as the acquired immunodeficiency syndrome-defining illness in a previously undiagnosed child. Pediatrics 2001;108(2):E39. [PMID: 11483849]

Marin M, Guris D, Chaves SS, Schmid S, Seward JF. Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2007;56(Rr-4):1-40. [PMID: 17585291]

Rubin LG, Levin MJ, Ljungman P, Davies EG, Avery R, Tomblyn M, Bousvaros A, Dhanireddy S, Sung L, Keyserling H, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis 2014;58(3):e44-100. [PMID: 24311479]

Zoster

Medical Care Criteria Committee, April 2018

Table 13: Zoster Vaccine
Trade Names Shingrix: Recombinant zoster vaccine (RZV), adjuvanted—PREFERRED
Indications Medical Care Criteria Committee recommendation: Patients with HIV ≥50 years of age (A2)
Administration
  • Two IM doses, spaced 2 to 6 months apart, regardless of past receipt of zoster live vaccine (ZVL)
  • RZV is preferred over the ZVL [Dooling et al. 2018] (AII)
  • Perform anti-varicella IgG screening in patients with no known history of chickenpox or shingles
Comments
  • RZV provides strong protection against shingles and post-herpetic neuralgia. Currently, there are no data on immunogenicity specific to people with HIV; however, superior efficacy and longer duration of protection have been demonstrated among the elderly, and a recombinant vaccine is preferred people with HIV. In addition, immunogenicity and safety following a 3-dose schedule has been demonstrated among people with HIV infection [Berkowitz et al. 2015].
  • Note: RZV is administered IM in distinction to ZVL which is delivered by SQ injection [Shimabukuro et al. 2018].
  • ZVL (brand name Zostavax) is also available, but is not recommended for people with HIV, and is contraindicated in patients with CD4 count <200 cells/mm3 (see the CDC’s Recommended Immunization Schedule for Adults Aged 19 Years or Older, United States 2018).
  • If RZV is not available and ZVL must be administered:
    • Perform anti-varicella IgG screening in patients with no known history of chickenpox or shingles
    • Instruct patients to avoid antiherpetic agents for 1 to 2 days before vaccination through 14 days after [Marin et al. 2007]
    • Separate administration of ZVL from administration of pneumococcal vaccine by at least 4 weeks [Zostavax 2017]

Discussion: Patients with HIV are at increased risk of zoster (initial episodes and recurrences) at all stages of HIV disease; the risk is greater among those with severe immunodeficiency and lower CD4 cell counts [Harpaz et al. 2008; Blank et al. 2012]. Zoster vaccination may reduce disease burden in individuals with HIV; however, data on the use of zoster vaccine among adults with HIV are limited.

The Advisory Committee on Immunization Practices recommends the RZV for use in immunocompetent adults aged ≥50 years. As noted above, this Committee recommends two doses of RZV, administered 2 to 6 months apart, for adults with HIV ≥50 years of age. RZV provides strong protection against shingles and post-herpetic neuralgia. There is no specific data on immunogenicity in people with HIV, however superior efficacy and longer duration of seroprotection have been demonstrated in the elderly, and a recombinant vaccine is preferred over a live attenuated vaccine in this population [Dooling et al. 2018].

Limited data are available on the immunogenicity of live attenuated zoster vaccine in people with HIV (ZVL). The Committee does not recommend use of ZVL in people with HIV due to the potential for adverse effects and for interference by co-administered antiviral and immune globulin therapy [Benson et al. 2012; Shafran 2016]. If ZVL is used due to lack of access to RZV, CDC guidelines recommend that, if possible, antiherpetic agents should be avoided 1 to 2 days before through 14 days after administration of the zoster vaccine [Harpaz et al. 2008]. In addition, zoster vaccine should be separated from pneumococcal vaccine by at least 4 weeks [Zostavax 2017]. Anti-varicella IgG screening should be performed in patients with no known history of chickenpox or shingles. Zoster vaccination is contraindicated for patients with CD4 counts <200 cells/mm3 [Harpaz et al. 2008]. There is no recommendation for post-vaccination serologic testing to determine immune response [Harpaz et al. 2008].

References

Benson CA, Hua L, W. AJ, Jiang JH, Bozzolo DR, Bergstrom K, Annunziato PW, Read SW, Pollard R, Rusin D, et al. Zostavax is generally safe and immunogenic in HIV-infected adults with CD4 counts ≥200 cells/μL virologically suppressed on ART: Results of a Phase 2, randomized, placebo-controlled trial. Oral abstract 96. CROI; 2012 Mar 5-8; Seattle, WA. http://www.viraled.com/modules/info/files/files_4f68abf5b1ba1.pdf

Berkowitz EM, Moyle G, Stellbrink HJ, Schürmann D, Kegg S, El Idrissi M, Oostvogeis L, Heineman TC, Zoster-015 HZ/su Study Group. Safety and immunogenicity of an adjuvanted herpes zoster subunit candidate vaccine in HIV-infected adults: a phase 1/2a randomizedplacebo-controlled studyJ Infect Dis. 2015 Apr 15;211(8):1279-87. [PMID: 25371534]

Blank LJ, Polydefkis MJ, Moore RD, Gebo KA. Herpes zoster among persons living with HIV in the current antiretroviral therapy era. J Acquir Immune Defic Syndr 2012;61(2):203-207. [PMID: 22766968]

Dooling KL, Guo A, Patel M, Lee GM, Moore K, Belongia EA, Harpaz R. Recommendations of the Advisory Committee on Immunization Practices for Use of Herpes Zoster Vaccines. MMWR Morb Mortal Wkly Rep 2018;67(3):103-108. [PMID: 29370152]

Harpaz R, Ortega-Sanchez IR, Seward JF. Prevention of herpes zoster: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2008;57(Rr-5):1-30; quiz CE32-34. [PMID: 18528318]

Marin M, Guris D, Chaves SS, Schmid S, Seward JF. Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2007;56(Rr-4):1-40. [PMID: 17585291]

Shafran SD. Live attenuated herpes zoster vaccine for HIV-infected adults. HIV Med 2016;17(4):305-310. [PMID: 26315285]

Shimabukuro TT, Miller ER, Strikas RA, et al. Notes from the Field: Vaccine Administration Errors Involving Recombinant Zoster Vaccine — United States, 2017–2018. MMWR Morb Mortal Wkly Rep 2018;67:585–586. [PMID: 29795075]

Zostavax. Package insert. 2017 Aug. https://www.merck.com/product/usa/pi_circulars/z/zostavax/zostavax_pi2.pdf [accessed 2018 Mar 27]

Summary of Recommended Vaccines for Adults with HIV

Medical Care Criteria Committee, April 2018

Click here to download full PDF version of the below table