INTRODUCTION — HIV infection, because of the immunocompromised state, is a risk factor for morbidity and mortality caused by a number of infections that can usually be prevented by immunization. A number of factors contribute to the HIV-infected patient's "net state of immunosuppression" including defects in cell-mediated immunity, B-cell dysfunction, and suboptimal humoral immune responses . In the absence of effective therapy, the immunocompromise is continually progressive. On the other hand, patients who respond to antiretroviral therapy (ART) have substantial increases in their CD4 cells, suggesting improved immunity.
Although vaccine efficacy is usually compromised in advanced disease, adequate responses can be achieved when vaccines are administered early after HIV infection . Concerns have been raised about vaccine safety, specifically the risk of activating the immune system and the potential for increasing HIV replication and promoting HIV infection. As discussed below, the benefits of administering vaccines appear to outweigh the risks.
Prevention of opportunistic infections is discussed in detail elsewhere. (See "Overview of prevention of opportunistic infections in HIV-infected patients".)
Treatment of these infections in general and in HIV-infected individuals is discussed in the dedicated topic reviews for each infection.
GUIDELINES — In 2013, the Infectious Diseases Society of America (IDSA) published guidelines for vaccination of immunocompromised hosts, including HIV-infected patients, as well as guidelines for the primary care of HIV-infected individuals, which discussed vaccinations [3,4]. Recommendations on immunization in HIV-infected patients have also been discussed in the guidelines on prevention of opportunistic infections in adults and adolescents from the Centers for Disease Control and Prevention (CDC), the National Institutes of Health, and the HIV Medicine Association of the IDSA  and in the guidelines on prevention of opportunistic infections in children from the US Department of Health and Human Services . The vaccine recommendations in the last two guidelines reflect the HIV-specific discussion in the general recommendations on immunization from the Advisory Committee on Immunization Practices (ACIP) in the United States .
The recommendations discussed in this topic are generally consistent with these guidelines above. Clinicians in other countries should refer to their national guidelines for recommendations regarding immunization of HIV-infected individuals.
GENERAL PRINCIPLES — Most data on vaccinations in HIV-infected individuals have examined immunogenicity rather than clinical efficacy. Overall, vaccines tend to be less immunogenic and antibody responses shorter-lived in the setting of HIV-infection. In general, protective antibodies are more likely elicited when vaccines are administered early in infection, prior to the decline in CD4 cell count, or after immune reconstitution and virologic suppression with antiretroviral therapy (ART).
Inactivated vaccines are generally safe and acceptable in HIV-infected individuals. Despite the greater immunogenicity in the setting of higher CD4 cell counts or virologic suppression with some vaccines, administration of inactivated vaccines does not have to be delayed if these have not yet been achieved; protective immunity with vaccination can be achieved in some patients despite immunosuppression, and the risk of infection is greatest in the setting of immunosuppression. However, if there was suboptimal antibody response to the initial vaccine, revaccination once immune reconstitution and virologic suppression has been achieved is recommended for certain vaccines.
Certain live vaccines have sufficient safety data and are thus recommended in HIV-infected patients who have CD4 cell percentage ≥15 percent (if <5 years old) or cell counts ≥200 cells/microL (if ≥5 years old). Live vaccines should not be given to HIV-infected individuals with CD4 cell parameters below these thresholds because of the absence of safety data and the concern about vaccine-associated infection.
All standard childhood vaccinations in the United States can be given to HIV-infected or exposed children, although certain live vaccinations (such as varicella vaccine and measles, mumps, and rubella [MMR] vaccines) should be limited to individuals without severe immunosuppression (ie, CD4 cell percentage ≥15 percent). HIV infection is an indication for meningococcal conjugate vaccination in infants and children.
Among adults, HIV-infected patients should receive the following categories of vaccines:
●Inactivated vaccines recommended for the general adult population:
•Inactivated seasonal influenza vaccine
•Tetanus toxoid and reduced diphtheria toxoid with or without acellular pertussis vaccine (Td or TdaP)
•Human papillomavirus (HPV) vaccination (up to age 26 in HIV-infected patients, if not received previously)
●Vaccines for which HIV is itself an indication:
•Hepatitis B virus (HBV) vaccine (if not already immune)
●Other vaccines are recommended for HIV-infected adults only if there is a specific indication or if there is evidence of no immunity:
•Hepatitis A virus (HAV) vaccine (if indicated)
•Haemophilus influenzae b vaccine (if indicated)
•Measles, mumps, rubella vaccine (if not already immune and CD4 cell count ≥200 cells/microL)
•Varicella vaccine (if not already immune and CD4 cell count ≥200 to 350 cells/microL)
Based on the results of one trial, zoster vaccine appears safe and immunogenic in HIV-infected adults with ≥200 cells/microL and virologic suppression on ART, but the optimal timing of vaccination is unclear . Guidelines from the HIV Medical Association of the Infectious Diseases Society of America IDSA in the United States suggest considering zoster vaccine in such patients older than 60 years. Zoster vaccine is contraindicated among those with CD4 cell counts <200 cells/microL.
For both HIV-infected children and adults, the recommendations on formulations, dosing, or schedules for specific immunizations may differ from those for the general population in an effort to optimize the vaccine response. The specific recommendations for each vaccine are discussed below.
Tetanus toxoid, diphtheria toxoid, and acellular pertussis vaccines — HIV-infected patients should receive tetanus, diphtheria, and pertussis immunizations based upon routine recommendations for adults and children . (See "Diphtheria, tetanus, and pertussis immunization in infants and children 0 through 6 years of age" and "Diphtheria, tetanus, and pertussis immunization in children 7 through 18 years of age" and "Tetanus-diphtheria toxoid vaccination in adults".)
Apart from the primary vaccine series, these recommendations include a single dose of a vaccine containing tetanus toxoid, reduced diphtheria toxoid, and reduced acellular pertussis (Tdap) for all individuals aged 11 years and older who have not received Tdap previously to address waning immunity against pertussis [9,10]. Universal administration of tetanus toxoid and reduced diphtheria toxoid (Td) boosters every 10 years is also recommended because of waning immunity against tetanus and diphtheria over time .
Additionally, all pregnant women should receive vaccination against pertussis with Tdap during each pregnancy . (See "Immunizations during pregnancy", section on 'Tetanus, diphtheria, and pertussis vaccination'.)
Several studies have evaluated the immunogenicity of these vaccines in HIV-infected patients, but the results are difficult to compare because of the various vaccine formulations and schedules used. In general, immunogenicity appears somewhat lower and shorter-lived than that observed among the general population [3,12]. HIV-infected adults have similar antibody response to tetanus as an age-matched normal population, but diphtheria immunity is lower than expected . Among those with advanced HIV infection, the response to immunization with both tetanus and diphtheria is lower compared with the general population, since the immune responses to tetanus and diphtheria are T cell-dependent [14,15].
These vaccinations are safe among the HIV-infected . One study noted a transient increase in plasma HIV-1 RNA levels after immunization with tetanus toxoid, but there were no long-term consequences of this upregulation .
Pneumococcal vaccine — Vaccination against Streptococcus pneumoniae is recommended for all HIV-infected patients (table 1). In general, HIV-infected individuals older than two years should receive at least one dose of the 13-valent conjugate vaccine (PCV13) [3,5,6]. Unless previously administered, the polysaccharide vaccine (PPSV23) should be given at least eight weeks after the PCV13, as a "prime boost" strategy . Revaccination is subsequently performed with PPSV23 at least five years after the initial PPSV23 dose. PCV13 can be given at any CD4 cell count, but it may be preferable to defer PPSV23 administration until the CD4 cell count ≥200 cells/microL.
Detailed discussion and specific recommendations for type and schedule of pneumococcal vaccination among HIV-infected patients are found elsewhere. (See "Pneumococcal immunization in HIV-infected adults", section on 'Vaccine recommendations' and "Pneumococcal (Streptococcus pneumoniae) conjugate vaccines in children".)
Haemophilus influenzae vaccine — Children with HIV infection should receive vaccination against Haemophilus influenzae type B (Hib) as recommended for the general, uninfected pediatric population [3,6] (see "Prevention of Haemophilus influenzae type b infection", section on 'Routine childhood immunization in the US'). In addition, HIV-infected children ages 5 through 18 can receive a single dose of a conjugate Hib vaccine if they have not already been vaccinated. Hib vaccine is not specifically recommended for HIV-infected adults unless a separate specific indication (eg, asplenia) is present .
As with other conjugate vaccines, antibody responses with the conjugate Hib vaccine in HIV-infected children have been disappointing. In one study, for example, only 37 percent of children seroconverted after administration of the Hib conjugate vaccine , and another report noted a lesser antibody response than controls, particularly in children with AIDS . The duration of the antibody response in children is unknown. In the United States, however, Hib remains rare among HIV-infected children despite the suboptimal immune response, likely in part because of herd immunity conferred by routine Hib vaccination of all children [6,20].
Similarly, the incidence of Hib disease in HIV-infected adults is fortunately low. Adults with advanced HIV disease do have a significantly increased rate of infection with H. influenzae, but most infections involve non-typeable strains for which the vaccine is not protective.
Influenza vaccine — Annual administration of the seasonal influenza vaccine is recommended for all HIV-infected patients aged six months and older [3,5,6,21]. The inactivated vaccine formulation is recommended for the 2016 to 2017 influenza season; live, intranasal vaccines should not be used in HIV-infected patients. The specific schedule and inactivated vaccine components are the same as for the general population and are discussed elsewhere. (See "Seasonal influenza vaccination in adults" and "Seasonal influenza in children: Prevention with vaccines".)
Efficacy, immunogenicity, and safety — Several studies have demonstrated the efficacy and safety of influenza vaccine [22-31]. In a systematic review of studies evaluating the efficacy of influenza vaccination, the rate of influenza-like illness (in 13 studies) and laboratory confirmed influenza (in four studies) was lower among vaccinated compared with unvaccinated HIV-infected patients; the rate of influenza-like illness was comparable to that in vaccinated patients without immune compromise . The following studies were included in the analysis:
●In a placebo-controlled trial of 102 HIV-infected patients, influenza vaccination resulted in significant reductions in respiratory symptoms (29 versus 49 percent) and laboratory-confirmed infection (0 versus 21 percent) .
●In a prospective study of 328 patients who were advised to have influenza vaccine, vaccination was associated with a lower risk of subsequent laboratory-confirmed influenza among the 262 who agreed to immunization compared with the 66 who did not (relative risk 0.29) .
In some studies, antibody responses following standard-dose influenza vaccines have been lower in HIV-infected individuals than in immunocompetent hosts [32,33]. An important question is whether using a high-dose influenza vaccine will improve immunogenicity and efficacy in HIV-infected individuals. The question of immunogenicity was addressed in a randomized trial that compared a standard dose (15 mcg of antigen per strain) with a high dose (60 mcg per strain) of the inactivated trivalent influenza vaccine in HIV-infected individuals . Seroprotection rates following vaccination were significantly higher in the high-dose group for the H1N1 influenza A (96 versus 87 percent) and influenza B (91 versus 80 percent) components but not for H3N2 influenza A (96 versus 92 percent, a non-significant difference). Further studies are warranted to evaluate the efficacy of the high-dose influenza vaccine in HIV-infected adults. Intradermal delivery of influenza vaccine, another strategy to increase immunogenicity, did not improve seroconversion rates compared with intramuscular delivery in a trial of HIV-infected men in Thailand . (See "Seasonal influenza vaccination in adults", section on 'High-dose vaccine' and "Seasonal influenza vaccination in adults", section on 'Intradermal delivery'.)
There are conflicting results as to whether influenza vaccination leads to a transient upregulation of HIV replication [23-27,32]. There are no studies to suggest any negative effect on HIV disease progression. The safety of the influenza vaccine in general is discussed separately. (See "Seasonal influenza vaccination in adults", section on 'Inactivated vaccines'.)
Risk factors for poor response — Since the antibody response to vaccination is critically dependent upon CD4 cell function, a poor vaccine response can be expected in patients with HIV, particularly those with advanced disease. Loss of CD4 cells is associated with weak influenza-specific antibody responses, as measured by titers and influenza-specific antibody secreting cells [14,22,36]. In fact, use of the vaccine has been questioned for patients with more advanced disease on a cost-benefit basis .
As in other vaccine studies in HIV-infected patients (eg, hepatitis B), the presence of circulating HIV RNA has also been demonstrated to be an important predictor of nonresponse to influenza vaccination . This suggests that the immunogenicity of the vaccine may be improved with viral suppression on antiretroviral therapy (ART).
Hepatitis A vaccine
Indications and administration — Vaccination against the hepatitis A virus (HAV) is recommended for susceptible HIV-infected patients who have chronic liver disease or are at increased risk for HAV infection [4,5,7,39]. These patients include (see "Hepatitis A virus infection: Treatment and prevention", section on 'Dosing and administration'):
●Patients with chronic hepatitis B or C virus infections
●Injection drug users
●Men who have sex with men (MSM)
●Travelers to countries with high endemicity of HAV (with the vaccine given at least two weeks prior to travel)
●Hemophiliacs and other individuals who receive clotting factor concentrates
Based on data suggesting improved immunogenicity with higher CD4 cell counts, HAV vaccination should be given early in the course of HIV infection prior to the decline of the CD4 cell count, if possible. Additionally, United States guidelines on the prevention of opportunistic infections in adults recommend that the anti-HAV antibody response should be assessed one month after vaccination . Patients without adequate antibody response should then be revaccinated when the CD4 cell count is ≥200 cells/microL.
Dosing and schedules depends on the patient’s age and formulation of vaccine used. If hepatitis B vaccination is also indicated, the combination hepatitis A and B vaccine (Twinrix) can be used. These issues are discussed elsewhere. (See "Hepatitis A virus infection: Treatment and prevention", section on 'Dosing and administration'.)
Prevaccination screening for HAV antibodies to identify susceptible individuals is cost-effective when expected prevalence rates are greater than 30 percent (eg, in persons older than 40 years) .
Immunogenicity and safety — Hepatitis A vaccine is immunogenic in HIV-infected patients, although in general, seroconversion rates are lower than those in HIV-uninfected patients [40-42]. This is particularly true in the setting of advanced immunosuppression [40,43,44].
●Immunization efficacy was studied in 90 HIV-infected adults and 90 uninfected subjects who were given an inactivated HAV vaccine (VAQTA) at weeks 0 and 24 of the study . Seroconversion rates at week 28 were 94 percent among the HIV-infected subjects compared with 100 percent in uninfected controls. The seroconversion rate was only 87 percent in HIV-infected subjects with a CD4 count <300/microL compared with 100 percent in those with a CD4 count ≥300/microL.
●In a study of 133 HIV-infected patients, seroconversion after two doses of inactivated HAV vaccine was demonstrated in 68 percent of those with CD4 counts >200 cells/microL compared with only 9 percent in those with lower CD4 cell counts .
In 214 patients undergoing HAV immunization, a multivariate analysis identified that the only predictor of vaccine efficacy was the absolute CD4 cell count; the past nadir CD4 cell count did not have any impact on immunogenicity . Additionally, there are conflicting data on whether the presence of HIV viremia at the time of immunization affects vaccine efficacy [42,45].
Among those who do respond, protective antibodies persist for at least several years [12,42,46]. In a systematic review of five studies, the pooled rates of anti-HAV seropositivity among initial responders were 92 and 82 percent at two and five years, respectively .
HAV vaccination is safe in HIV-infected patients and does not affect clinical progression or levels of HIV plasma viremia [40,43,47,48].
Hepatitis B vaccine — Routine screening for and immunization against hepatitis B virus (HBV) is recommended for all HIV-infected individuals to prevent primary infection [5,7,49]. All HIV-infected patients are at increased risk of hepatitis B virus (HBV) infection due to shared modes of transmission. Furthermore, HIV-infected individuals are less likely to clear HBV DNA and are at increased risk of chronic infection .
The approach to HBV vaccination in HIV-infected patients includes identifying HBV-susceptible adults through serologic screening, optimizing the timing and dosing of vaccinations for adults and children, and routinely checking serologic response to identify those individuals who might benefit from repeat vaccination. Because of the increased risk of HBV infection and the suboptimal immune response to HBV vaccination in HIV-infected patients, various strategies have been recommended in an attempt to improve rates of protection. These issues are discussed in detail elsewhere. (See "Prevention of hepatitis B virus infection in the HIV-infected adult" and "Hepatitis B virus immunization in infants, children, and adolescents", section on 'Routine infant immunization'.)
Meningococcal vaccine — Vaccination with meningococcal conjugate vaccine (MenACWY-CRM [Menveo] or MenACWY-D [Menactra], which include serogroups A, C, W, and Y) is recommended for all HIV-infected individuals two months of age or older [3,51]. In addition, serogroup B meningococcal vaccination may also be indicated (eg, in the United States, it is recommended for those with persistent complement component deficiencies or anatomic or functional asplenia, for microbiologists routinely exposed to isolates of Neisseria meningitidis, and in the setting of outbreaks of serogroup B meningococcal disease). (See "Meningococcal vaccines", section on 'Routine vaccination' and "Meningococcal vaccines", section on 'Serogroup B'.)
Administration — The recommended schedule for meningococcal conjugate vaccination for HIV-infected individuals varies by age .
●Younger than two years – The schedule depends on the specific conjugate vaccine used:
•Four doses of MenACWY-CRM (Menveo) at 2, 4, 6, and 12 to 15 months (those who initiate the vaccine series after seven months should receive two doses 12 weeks apart, with the second dose administered after the first birthday) OR
•Two doses of MenACWY-D (Menactra) at 9 to 23 months 12 weeks apart
●Two years or older – The schedule depends on prior receipt of meningococcal conjugate vaccination:
•For those who have had no prior vaccination, two doses of MenACWY-CRM or MenACWY-D are given 8 to 12 weeks apart.
•For those who have had prior vaccination, a booster dose with MenACWY-CRM or MenACWY-D is administered. It is given three years later if the most recent dose was received prior to age seven; otherwise, it is given every five years.
Either MenACWY-CRM or MenACWY-D can be used in HIV-infected individuals, and the choice between them depends on availability and clinician familiarity. If MenACWY-D is used, it should be administered at least four weeks after pneumococcal conjugate vaccine and in children should be administered before or at the same time as DTaP.
For those who have indications for serogroup B vaccination, either serogroup B vaccine (Truemba or Bexsero) can be used, but the same vaccine should be used throughout the series. (See "Epidemiology of Neisseria meningitidis infection", section on 'Outside the United States' and "Epidemiology of Neisseria meningitidis infection", section on 'Serogroup C in men who have sex with men'.)
This schedule is based on immunogenicity studies that demonstrate improved antibody responses with two vaccine doses but waning immunity over time. (See 'Immunogenicity and safety' below.)
Rationale — The main rationale for meningococcal vaccination is the risk of invasive meningococcal disease in HIV-infected individuals. Data on the efficacy of meningococcal vaccination in this population are limited to immunogenicity studies.
Growing evidence has suggested that HIV-infected individuals have a higher risk for invasive meningococcal disease, with an estimated relative risk of 5 to 13 times that of the general population [51-53]. As an example, in a retrospective database study, the estimated annual incidence of invasive meningococcal infection in New York City between 2000 and 2011 was 0.39 cases per 100,000 persons overall and 3.4 per 100,000 persons among the HIV-infected . The risk was especially high among those with CD4 counts <200 cells/microL. (See "Epidemiology of Neisseria meningitidis infection", section on 'HIV infection'.)
In particular, HIV-infected MSM are at high risk of exposure and infection if they have close contact (including meeting at a bar, party, or through online applications) with other MSM in locations where meningococcal outbreaks among MSM have been reported (including New York City, Los Angeles, Chicago, and certain European cities) [54-59]. (See "Epidemiology of Neisseria meningitidis infection", section on 'Serogroup C in men who have sex with men'.)
Although efficacy of meningococcal conjugate vaccine in preventing invasive disease has not been established in HIV-infected individuals and immunogenicity has only been evaluated in HIV-infected individuals younger than 25 years, in those studies, vaccination elicited protective immune response in the majority, and serious adverse events were rare. Improved vaccine responses with two conjugate vaccine doses compared with one and waning immunity inform the recommended vaccine schedule. (See 'Immunogenicity and safety' below.)
Immunogenicity and safety — The immunogenicity of meningococcal conjugate vaccine has not been specifically studied in HIV-infected adults older than 24 years and is extrapolated for this age group from studies among younger patients. In children without low CD4 cell counts, a single dose of meningococcal conjugate vaccine elicited antibody responses that were generally lower than in HIV-uninfected patients and varied by serogroup but exceeded protective levels in the majority of patients [60,61]. In a separate randomized trial of HIV-infected adolescents and young adults aged 11 to 24 years, protective levels were also achieved in the majority . Two conjugate vaccine doses resulted in higher rates of protective immune responses than a single dose, although the differences in rates decreased by 72 weeks post-vaccination; immune responses were poor among the small group of patients with CD4 cell percentage <15 despite two doses. Thus, for HIV-infected individuals two doses are recommended for the primary vaccine series, with subsequent interval boosting doses because of waning immunity. (See 'Administration' above.)
Only one serious adverse event in these studies was thought to be potentially related to vaccine receipt (migraine and ocular pain) .
Human papillomavirus vaccine — Vaccination against human papillomavirus (HPV) is recommended for all adolescents (HIV-infected and uninfected) at the ages of 11 or 12. For HIV-infected females and males, HPV vaccination is also recommended in those aged 13 through 26 who did not get any or all doses when they were younger [5,7]. HIV-infected patients are more likely to have HPV infection and HPV-associated diseases compared with the uninfected. (See "Human papillomavirus infections: Epidemiology and disease associations", section on 'Effect of HIV infection on HPV' and "Preinvasive and invasive cervical neoplasia in HIV-infected women" and "Anal squamous intraepithelial lesions: Diagnosis, screening, prevention, and treatment", section on 'HIV infection'.)
Formulations of HPV vaccine include the 9-valent (Types 6, 11, 16, 18, 31, 33, 45, 52, and 58), the quadrivalent (Types 6, 11, 16, 18) and bivalent (Types 16, 18) vaccines. In the United States, only the 9-valent vaccine is available.
Although the maximum age for vaccination is 26, because this was the upper age range of patients included in vaccine trials, some experts vaccinate HIV-infected patients, particularly MSM, beyond this age because of the greater risk of disease in this population.
The safety and immunogenicity of HPV vaccines have been studied and documented among several populations of HIV-infected individuals [63-65]. (See "Human papillomavirus vaccination", section on 'Immunocompromised hosts'.)
HPV testing prior to vaccination is not necessary. A history of genital warts, abnormal cytology, or positive HPV DNA test result is not evidence of prior infection with any or all of the vaccine HPV types and thus should not preclude vaccination if indicated by age .
A detailed discussion regarding HPV vaccination can be found elsewhere. (See "Human papillomavirus vaccination", section on 'Immunocompromised hosts'.)
Poliovirus vaccine — HIV-infected infants and children should receive inactivated polio vaccine as recommended for the general population. The small number of HIV-infected adults at risk of exposure to polio (by travel or work) should receive a primary series IPV if there is no documentation of vaccination status . A single lifetime booster with IPV is recommended for adults at continued risk of exposure to polio although the duration of protection is unknown . (See "Poliovirus vaccination".)
Rotavirus vaccine — Rotavirus vaccination is not contraindicated in HIV-infected or exposed infants and is generally supported by expert groups [3,6]. Dosing and schedule recommendations are the same as for uninfected infants. (See "Rotavirus vaccines for infants", section on 'Precautions' and "Rotavirus vaccines for infants", section on 'Schedule'.)
Measles, mumps, and rubella vaccine — Vaccination for measles, mumps, and rubella (MMR) is recommended for HIV-infected children without evidence of severe immunosuppression (ie, CD4 cell percentage ≥15 percent) [3,6,67]. A detailed discussion of MMR vaccination in HIV-infected children is discussed elsewhere. (See "Measles, mumps, and rubella immunization in infants, children, and adolescents", section on 'HIV infection without severe immunosuppression'.)
For older children and adults with newly diagnosed HIV infections who are without acceptable evidence of MMR immunity, two doses of MMR vaccine, given at least 28 days apart, are recommended unless they have evidence of severe immunosuppression (ie, CD4 percentage <15 percent or, if older than five years, a CD4 count <200 cells/microL) . Acceptable evidence of immunity includes birth before 1957, history of prior vaccination, or laboratory evidence of immunity or disease.
Administration of MMR vaccine is not recommended in HIV-infected patients with severe immunosuppression [3,67]. Additionally, administration of the measles, mumps, rubella, and varicella combination vaccine is not recommended in HIV-infected patients as it has not been studied in this population.
Measles can be a life-threatening infection in immunocompromised patients. In the pre-antiretroviral therapy (ART) era, the case-fatality rate for patients with HIV was reported to be as high as 40 percent . Since the number of measles cases has been increasing in the United States, as well as in other countries, prevention of measles in HIV infection is of major importance. (See "Measles: Epidemiology and transmission".)
The MMR vaccine is safe in HIV-infected patients without severe immunosuppression [69,70]. However, the antibody response to MMR vaccine in HIV-infected children and adults is low, even among those receiving ART [69,71,72], although in one study of children on ART, a second MMR dose improved protective antibody development .
The majority of HIV-infected adults are seropositive to measles, even if the CD4 cell count is <200 cells/microL , suggesting that protective antibodies elicited by MMR vaccination prior to HIV infection are not substantially effected by HIV-associated immune decline.
Indications and administration — Varicella vaccine is recommended for HIV-infected children who do not have evidence of severe immunosuppression (ie, CD4 cell percentage ≥15 percent) [3,5,6]. In addition, we recommend administration of varicella vaccine to HIV-infected adults and adolescents with CD4 cell counts ≥200 cells/microL if they were born after 1979 and do not have evidence of immunity (anti-varicella immunoglobulin G [IgG] antibody levels) or a history of two prior doses of the varicella vaccine administered when their CD4 counts were ≥200 cells/microL. For those with CD4 counts less than 200 cells/microL, we recommend deferring the varicella vaccine until the counts are above that threshold. This is consistent with Advisory Committee on Immunization Practices (ACIP) and Infectious Diseases Society of America (IDSA) recommendations to consider varicella vaccination in HIV-infected adults and adolescents without immunity to varicella-zoster virus who have CD4 cell counts ≥200 cells/microL [3,5-7].
Administration of varicella vaccine is not recommended in HIV-infected patients with severe immunosuppression (ie, CD4 cell percentage <15 percent or, if older than five years, a CD4 count <200 cells/microL) [3,5-7]. Additionally, administration of the measles, mumps, rubella, and varicella combination vaccine is not recommended in HIV-infected patients as it has not been studied in this population.
Postexposure prophylaxis following exposure to varicella-zoster virus is indicated for HIV-infected individuals who do not have immunity through natural infection or immunization. This is discussed in detail elsewhere. (See "Post-exposure prophylaxis against varicella-zoster virus infection".)
Immunogenicity and safety — Primary varicella can cause severe illness in HIV-infected children and adults . Varicella vaccine has been demonstrated to be safe , effective , and immunogenic in asymptomatic HIV-infected children with CD4 percentages of 25 percent or more [76-79]. One study evaluated the safety and efficacy of varicella vaccine in children with a history of severe immunosuppression who had achieved immune reconstitution (n = 17) and in those with moderate symptoms and CD4 percentages ≥15 percent (n = 37) . Regardless of immunologic category, 79 percent of HIV-infected vaccine recipients developed varicella zoster virus-specific antibody and/or cell-mediated immunity 60 days after the immunization series. A multivariate analysis indicated that detectable HIV viremia at baseline correlated with a lower likelihood of immunization response.
Varicella vaccine has not been studied systematically in adults, but most experts feel that adult patients with clinically stable HIV infection and a CD4 count ≥200 cells/microL would have comparable immunity to the HIV-infected children described above.
In studies in children, varicella vaccination did not affect the CD4 cell percentage or plasma viral level [77,80].
Other risks associated with varicella vaccination are discussed elsewhere. If vaccination results in disease because of vaccine virus, therapy with acyclovir is recommended . (See "Vaccination for the prevention of chickenpox (primary varicella infection)", section on 'Adverse events'.)
Zoster vaccine — Two zoster vaccines are available, a non-live recombinant zoster vaccine (RZV) and a live zoster vaccine (ZVL). Studies on the efficacy and safety of RZV in HIV-infected patients are limited , and so the ACIP does not yet recommend its use in this population . It is reasonable to administer ZVL to those with CD4 counts >200 cells/microL who are aged 60 years or older . ZVL is specifically not recommended for HIV-infected patients with a CD4 cell count <200 cells/microL [7,82].
In a trial (ACTG 5247) of 295 HIV-infected individuals with CD4 cell counts ≥200 cells/microL and virologic suppression on ART, ZVL appeared safe and immunogenic . Individuals with CD4 cell counts >350 cells/microL had the highest zoster antibody levels post-vaccination. However, there were higher rates of injection site reactions in the vaccine group (42 versus 12.4 percent in the placebo group). Although these data are promising, it is not yet clear which HIV-infected individuals at what age should receive ZVL.
Zoster vaccination is discussed in detail elsewhere. (See "Vaccination for the prevention of shingles (herpes zoster)".)
Yellow fever vaccine — Yellow fever vaccine can be administered, if indicated, to HIV-infected patients with CD4 cell counts ≥200 cells/microL . However, it is contraindicated in patients with lower CD4 cell counts due to concerns regarding risk of live virus vaccine in patients with advanced immunosuppression.
In a systematic review of observational studies that included approximately 450 HIV-infected patients (most of whom had CD4 cell counts ≥200 cells/microL), there were no serious adverse events reported .
Although yellow fever vaccine appears to be safe among HIV-infected patients without severe immunosuppression, it is less immunogenic than among uninfected individuals [85,86]. In a retrospective study of 102 patients from the Swiss HIV Cohort who were identified who had received yellow fever vaccine, protective antibodies were detected less frequently and at lower neutralization titers compared with a separate cohort of uninfected patients .
In one prospective study of 240 HIV-infected patients who received yellow fever vaccine after their HIV diagnosis, failure to achieve a significant level of neutralizing antibodies was associated with detectable HIV RNA at the time of immunization . There are conflicting data as to whether the level of immunosuppression is associated with vaccine immunogenicity [86,87].
BCG vaccine — Bacillus Calmette Guerin (BCG) vaccines are administered to newborn infants in developing countries to reduce the risk of developing tuberculosis. Although HIV-infected patients are at risk of developing tuberculosis, disseminated BCG has been reported after vaccination , with complications occurring up to many years after vaccination [89,90]. Since the efficacy of the vaccine in HIV-infected patients is unknown and there is a risk of disseminated disease, two Centers for Disease Control and Prevention (CDC) advisory groups have recommended against use of the BCG vaccine even if the risk of acquiring tuberculosis is high .
Preliminary data from a randomized placebo-controlled trial among 2013 HIV-infected patients in Tanzania suggest that an inactivated whole cell mycobacterial vaccine (Mycobacterium vaccae) is safe and protects against tuberculosis infection .
PASSIVE IMMUNIZATION — Since HIV-infected patients with low CD4 cell counts may not be able to make effective new antibodies despite vaccination, the use of hyperimmune globulin preparations can be considered in some immunocompromised patients following high-risk exposures, such as to varicella, hepatitis A, or measles. (See "Post-exposure prophylaxis against varicella-zoster virus infection", section on 'Passive immunization' and "Hepatitis A virus infection: Treatment and prevention", section on 'Protection following exposure' and "Measles, mumps, and rubella immunization in adults", section on 'Postexposure prophylaxis'.)
Immunizations in travelers — Immunizations in travelers are discussed separately. The use of the different vaccines must be considered in relation to the issues described above. (See "Immunizations for travel".)
Immunizations in pregnant women — HIV-infected pregnant women should receive the routine vaccinations recommended during pregnancy in general, namely the inactivated seasonal influenza vaccine and the tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine. Receipt of other vaccines that may be indicated because of HIV-infection or a different comorbidity depend on the recommendations for administration during pregnancy. These are discussed in detail elsewhere. (See "Immunizations during pregnancy".)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Immunizations in HIV-infected patients" and "Society guideline links: Immunizations in adults".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Beyond the Basics topic (see "Patient education: Adult vaccines (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●HIV infection is associated with increased risk of a number of infections that can often be prevented by immunization. HIV-infected patients have defects in cell-mediated immunity, B-cell dysfunction, and suboptimal humoral immune responses. (See 'Introduction' above.)
●Antibody responses to vaccines are generally less robust among HIV-infected persons compared with the uninfected. Thus, for HIV-infected patients, specific formulations, dosing, and schedules of vaccines, as well as post-vaccine evaluation of antibody responses, are utilized to optimize their impact. (See 'General principles' above.)
●All standard childhood immunizations in the United States can be given to HIV-infected or exposed children, although certain live vaccines (such as varicella vaccine and measles, mumps, and rubella [MMR] vaccines) should be limited to individuals who are not severely immunosuppressed (ie, CD4 cell percentage ≥15 percent). (See 'General principles' above.)
●HIV-infected adults should receive seasonal influenza vaccine and tetanus, diphtheria, and pertussis immunizations according to routine recommendations for the general population (figure 1). (See 'Influenza vaccine' above and 'Tetanus toxoid, diphtheria toxoid, and acellular pertussis vaccines' above.)
●Human papillomavirus (HPV) vaccine should be given to HIV-infected individuals through age 26 years who did not receive any or all doses when they were younger. HPV DNA screening is not recommended prior to immunization. (See 'Human papillomavirus vaccine' above and "Human papillomavirus vaccination", section on 'Immunocompromised hosts'.)
●HIV-infected adults should receive immunization for pneumococcal infection with both the 13-valent conjugate (PCV13) and polysaccharide (PPSV23) vaccines. (See 'Pneumococcal vaccine' above and "Pneumococcal immunization in HIV-infected adults".)
●HIV-infected adults who are not immune to hepatitis B virus (HBV) should receive the HBV vaccine series. Strategies to improve antibody response to the HBV vaccine include using a double dose of vaccine, checking for vaccine response, and revaccinating non-responders. (See 'Hepatitis B vaccine' above and "Prevention of hepatitis B virus infection in the HIV-infected adult".)
●HIV-infected adults who have chronic liver disease or are at increased risk for hepatitis A infection should receive the hepatitis A vaccine series if not already immune. Candidates for HAV vaccine include patients with chronic hepatitis B or C infection, injection drug users, men who have sex with men (MSM), and hemophiliacs. (See 'Hepatitis A vaccine' above.)
●We suggest meningococcal conjugate vaccination (Menactra or Menveo) for all HIV-infected individuals older than two months (Grade 2C). This is in agreement with the Advisory Committee on Immunization Practices (ACIP) in the United States. Meningococcal vaccination is administered as a primary series followed by interval boosting doses; the precise schedule depends on the age of the patient. Serogroup B meningococcal vaccination may also be indicated depending on patient risk factors. (See 'Meningococcal vaccine' above and "Meningococcal vaccines", section on 'Age <11 or age >18 years'.)
●Although HIV-infected patients have an increased rate of infection with Haemophilus influenzae, most involve non-typeable strains for which the vaccine is not protective. Thus, this vaccine is not recommended for HIV-infected adults who do not have other specific indications (eg, asplenia). Children with HIV infection should receive vaccination against H. influenzae type B (Hib) as recommended for the uninfected pediatric population. (See 'Haemophilus influenzae vaccine' above.)
●In general, live vaccines should not be given to HIV-infected individuals who have CD4 cell percentages <15 percent (if <5 years of age) or CD4 counts <200 cells/microL (if >5 five years of age), but several live vaccines are acceptable for non-immune patients with CD4 cell parameters above these thresholds. Live vaccines include MMR vaccine, varicella vaccine, yellow fever vaccine, and zoster vaccine. It is reasonable to administer live zoster vaccine (ZVL) to HIV-infected patients ≥60 years of age with CD4 cell counts ≥200 cells/microL, although data regarding efficacy are limited. (See 'Live vaccines' above.)
●Bacillus Calmette Guerin (BCG) vaccine is utilized in developing countries to reduce the risk of developing tuberculosis. Since there is a risk of disseminated tuberculosis disease after vaccination and the efficacy of BCG vaccine is unknown, it is not recommended in HIV-infected patients. (See 'BCG vaccine' above.)