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 patient with HIV's "net state of immunosuppression" including defects in cell-mediated immunity, B-cell dysfunction, and suboptimal humoral immune responses [1]. 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 and improved immunity.

Although vaccine efficacy is usually compromised in advanced disease, adequate responses can be achieved when vaccines are administered early after HIV infection [2] or after virologic suppression and immune reconstitution with ART. 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 outweigh the risks.

Prevention of opportunistic infections is discussed in detail elsewhere. (See "Overview of prevention of opportunistic infections in patients with HIV".)

Treatment of these infections in general and in individuals with HIV 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 patients with HIV, as well as guidelines for the primary care of individuals with HIV, which discussed vaccinations [3,4]. Recommendations on immunization in patients with HIV 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 [5] and in the guidelines on prevention of opportunistic infections in children from the US Department of Health and Human Services [6]. 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 (figure 1) [7].

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 individuals with HIV.

GENERAL PRINCIPLES — Most data on vaccinations in individuals with HIV 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 individuals with HIV. 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 patients with HIV 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 individuals with HIV and 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 children with or exposed to HIV, 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, patients with HIV should receive the following categories of vaccines:

●Vaccines recommended for the general adult population:

•Coronavirus disease-19 (COVID-19) vaccine

•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 years in patients with HIV, if not received previously)

●Vaccines for which HIV is itself an indication:

•Pneumococcal vaccination

•Hepatitis A virus (HAV) vaccine (if not already immune)

•Hepatitis B virus (HBV) vaccine (if not already immune)

•Meningococcal vaccination

●Other vaccines are recommended for adults with HIV only if there is a specific indication or if there is evidence of no immunity:

•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)

•Inactivated zoster vaccine (if ≥50 years old)

For both children and adults with HIV, 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.

COVID-19 VACCINES — Vaccines to prevent COVID-19 are considered the most promising approach for curbing the pandemic. We recommend that patients with HIV receive a COVID-19 vaccine if they are eligible according to local guidelines for vaccine allocation. COVID-19 vaccines are discussed in more detail elsewhere. (See "COVID-19: Vaccines", section on 'Approach to vaccination'.)

Trials of mRNA COVID-19 vaccines included small numbers of participants with well-controlled HIV [8,9], but overall data on the efficacy and safety of COVID-19 vaccines in this population are limited. Immunogenicity of the vaccines may be lower in patients with HIV, particularly those with CD4 cell counts <200 cells/microL, but whether this is the case is not yet known. Nevertheless, the benefit of COVID-19 vaccination likely still outweighs the potential risks in the setting of HIV. This applies to the mRNA vaccines as well as other globally available COVID-19 vaccines, none of which are live or replication competent.

Although it is uncertain whether HIV itself is a risk factor for severe COVID-19, other comorbidities (such as cardiovascular disease) that are associated with severe COVID-19 are common in individuals with HIV. This is discussed elsewhere. (See "COVID-19: Clinical features", section on 'People with HIV'.)

INACTIVATED VACCINES

Tetanus toxoid, diphtheria toxoid, and acellular pertussis vaccines — Patients with HIV should receive tetanus, diphtheria, and pertussis immunizations based upon routine recommendations for adults and children [5]. (See "Tetanus-diphtheria toxoid vaccination in adults" and "Diphtheria, tetanus, and pertussis immunization in children 7 through 18 years of age", section on 'Schedule' and "Diphtheria, tetanus, and pertussis immunization in children 6 weeks through 6 years of age", section on 'Indications'.)

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 [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 [7].

Additionally, all pregnant women should receive vaccination against pertussis with Tdap during each pregnancy [10]. (See "Immunizations during pregnancy", section on 'Tetanus, diphtheria, and pertussis vaccination'.)

Several studies have evaluated the immunogenicity of these vaccines in patients with HIV, 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 [3,11]. Adults with HIV have similar antibody response to tetanus as an age-matched normal population, but diphtheria immunity is lower than expected [12]. Among those with advanced HIV, 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 [13,14].

These vaccinations are safe among those with HIV [3]. 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 [15].

Pneumococcal vaccine — Vaccination against Streptococcus pneumoniae is recommended for all patients with HIV (table 1). In general, individuals with HIV older than two years of age 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 [16]. 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 patients with HIV are found elsewhere. (See "Pneumococcal immunization in adults with HIV", section on 'Vaccine recommendations' and "Pneumococcal vaccination in children", section on 'Immunization of high-risk children and adolescents'.)

Haemophilus influenzae vaccine — Children with HIV should receive vaccination against Haemophilus influenzae type B (Hib) as recommended for the general pediatric population without HIV [3,6] (see "Prevention of Haemophilus influenzae type b infection", section on 'Routine childhood immunization in the United States'). In addition, children with HIV ages 5 through 18 years can receive a single dose of a conjugate Hib vaccine if they have not already been vaccinated. Hib vaccine is not specifically recommended for adults with HIV unless a separate specific indication (eg, asplenia) is present [5].

As with other conjugate vaccines, antibody responses with the conjugate Hib vaccine in children with HIV have been disappointing. In one study, for example, only 37 percent of children seroconverted after administration of the Hib conjugate vaccine [17], and another report noted a lesser antibody response than controls, particularly in children with AIDS [18]. The duration of the antibody response in children is unknown. In the United States, however, Hib remains rare among children with HIV despite the suboptimal immune response, likely in part because of herd immunity conferred by routine Hib vaccination of all children [6,19].

Similarly, the incidence of Hib disease in adults with HIV 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 patients with HIV aged six months and older [3,5,6,20]. There is particular emphasis on administration of the influenza vaccine during the 2020-2021 influenza season because of continued circulation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); influenza vaccination should reduce the need for medical attention due to influenza and decrease the risk of coinfection with SARS-CoV-2 and influenza.

Live, intranasal vaccines should not be used in patients with HIV. The specific schedule and inactivated vaccine components are the same as those for the general population and are discussed elsewhere. As with the general adult population, if a trivalent formulation of the influenza vaccine is available immediately and the quadrivalent vaccine is not available, it is preferable to administer the trivalent vaccine rather than delay vaccination. (See "Seasonal influenza vaccination in adults".)

Efficacy, immunogenicity, and safety — Several studies have demonstrated the efficacy and safety of influenza vaccine [21-30]. 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 patients with HIV; the rate of influenza-like illness was comparable to that in vaccinated patients without immune compromise [31]. The following studies were included in the analysis:

●In a placebo-controlled trial of 102 patients with HIV, influenza vaccination resulted in significant reductions in respiratory symptoms (29 versus 49 percent) and laboratory-confirmed infection (0 versus 21 percent) [26].

●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) [21].

In some studies, antibody responses following standard-dose influenza vaccines have been lower in individuals with HIV than in immunocompetent hosts [31,32]. An important question is whether using a high-dose influenza vaccine will improve immunogenicity and efficacy in individuals with HIV. 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 individuals with HIV [33]. 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 adults with HIV. Intradermal delivery of influenza vaccine, another strategy to increase immunogenicity, did not improve seroconversion rates compared with intramuscular delivery in a trial of men with HIV in Thailand [34]. (See "Seasonal influenza vaccination in adults", section on 'High dose IIV' 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 [22-26,31]. 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".)

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 [13,21,35]. In fact, use of the vaccine has been questioned for patients with more advanced disease on a cost-benefit basis [36].

As in other vaccine studies in patients with HIV (eg, hepatitis B), the presence of circulating HIV RNA has also been demonstrated to be an important predictor of nonresponse to influenza vaccination [37]. 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 all susceptible patients with HIV ≥1 year old [7,38]. Previously, HAV vaccination was recommended only for patients with HIV who had certain other indications (including chronic B or C virus infection, injection drug use, being a man who has sex with men, homelessness); the recommendation was broadened in part because of the risk for longer duration of HAV viremia in the setting of HIV, the high prevalence of the prior indications among patients with HIV, and the limited additional harms with a broader vaccination approach [39].

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 [5]. 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) [5].

Immunogenicity and safety — Hepatitis A vaccine is immunogenic in patients with HIV, although in general, antibody seroconversion rates are lower than those in patients without HIV [40-42]. This is particularly true in the setting of advanced immunosuppression [40,43,44].

●Immunogenicity was studied in 90 adults with HIV and 90 subjects without HIV who were given an inactivated HAV vaccine (VAQTA) at weeks 0 and 24 of the study [40]. Antibody seroconversion rates at week 28 were 94 percent among the subjects with HIV compared with 100 percent in controls without HIV. The seroconversion rate was only 87 percent in subjects with HIV and a CD4 count <300/microL compared with 100 percent in those with a CD4 count ≥300/microL.

●In a study of 133 patients with HIV, 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 [43].

In 214 patients undergoing HAV immunization, a multivariate analysis identified that the only predictor of vaccine immunogenicity was the absolute CD4 cell count; the past nadir CD4 cell count did not have any impact on antibody seroconversion [45]. Additionally, there are conflicting data on whether the presence of HIV viremia at the time of immunization affects vaccine immunogenicity [42,45].

Among those who do respond, protective antibodies persist for at least several years [11,42,46]. 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 [11].

Providers should be aware that patients with HIV may still be at risk for HAV infection despite a reported history of complete or partial HAV vaccination. Although no studies have evaluated the efficacy of HAV vaccination in persons with HIV, a case report of an outbreak of HAV in Tennessee described 11 cases in patients with HIV [47]. Two patients had previously completed the entire series of HAV vaccine; four additional patients were incompletely vaccinated. HAV vaccination is safe in patients with HIV and does not affect clinical progression or levels of HIV plasma viremia [40,43,48,49].

Hepatitis B vaccine — Routine screening for and immunization against hepatitis B virus (HBV) is recommended for all individuals with HIV to prevent primary infection [5,7,50]. All patients with HIV are at increased risk of hepatitis B virus (HBV) infection due to shared modes of transmission. Furthermore, individuals with HIV are less likely to clear HBV DNA and are at increased risk of chronic infection [51].

The approach to HBV vaccination in patients with HIV 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 patients with HIV, 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 adults with HIV" 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 individuals with HIV two months of age or older [3,52]. 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 vaccination in children and adults", section on 'Serogroup B vaccines' and "Meningococcal vaccination in children and adults", section on 'Immunization of persons at increased risk'.)

Administration — The recommended schedule for meningococcal conjugate vaccination for individuals with HIV varies by age [52].

●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 individuals with HIV, 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 '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 individuals with HIV. Data on the efficacy of meningococcal vaccination in this population are limited to immunogenicity studies.

Growing evidence has suggested that individuals with HIV have a higher risk for invasive meningococcal disease, with an estimated relative risk of 5 to 13 times that of the general population [52-54]. 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 those with HIV [53]. 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, MSM with HIV 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) [55-60]. (See "Epidemiology of Neisseria meningitidis infection", section on 'Men who have sex with men'.)

Although efficacy of meningococcal conjugate vaccine in preventing invasive disease has not been established in individuals with HIV, and immunogenicity has only been evaluated in individuals with HIV 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 adults with HIV 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 patients without HIV and varied by serogroup but exceeded protective levels in the majority of patients [61,62]. In a separate randomized trial of adolescents and young adults with HIV aged 11 to 24 years, protective levels were also achieved in the majority [63]. 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 individuals with HIV, 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) [63].

Human papillomavirus vaccine — Vaccination against human papillomavirus (HPV) is recommended for all adolescents (with and without HIV) at the ages of 11 or 12 and for individuals aged 13 through 26 who did not get any or all doses when they were younger [64]. HPV vaccination may also be of benefit in select older individuals who had not been previously vaccinated. Patients with HIV are more likely to have HPV infection and HPV-associated diseases compared with those without HIV. (See "Human papillomavirus infections: Epidemiology and disease associations", section on 'Effect of HIV infection on HPV' and "Preinvasive and invasive cervical neoplasia in patients with HIV infection" and "Anal squamous intraepithelial lesions: Epidemiology, clinical presentation, diagnosis, screening, prevention, and treatment", section on 'HIV'.)

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 patients with HIV, 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 individuals with HIV [65-67]. (See "Human papillomavirus vaccination", section on 'Patients with HIV or immunocompromising conditions'.)

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 [7].

A detailed discussion regarding HPV vaccination can be found elsewhere. (See "Human papillomavirus vaccination", section on 'Patients with HIV or immunocompromising conditions'.)

Zoster vaccine — Two zoster vaccines are available, a non-live recombinant zoster vaccine (RZV) and a live zoster vaccine (ZVL). Although the ACIP has not yet formally recommended vaccination to prevent herpes zoster in people with HIV, we agree with recommendations from the US Department of Health and Human Services that adults with HIV 50 years and older receive RZV [68]. The dosing schedule for RZV is by two intramuscular injections separated by at least eight weeks. If RZV is not available or there is an intolerance or allergy to RZV, ZVL can be given as a single intramuscular injection to patients with a CD4 cell count ≥200 cells/microL.

Studies on the efficacy and safety of RZV in patients with HIV are limited [69]. Small early phase trials suggest that RZV is safe and immunogenic in patients with HIV [69]. Data in immunocompetent patients that demonstrate greater efficacy of RZV compared with ZVL also support the preference for RZV in the HIV population. (See "Vaccination for the prevention of shingles (herpes zoster)".)

In a trial of 395 individuals with HIV, CD4 cell counts ≥200 cells/microL, and virologic suppression on ART, ZVL appeared safe and immunogenic [70]. 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).

Zoster vaccination is discussed in detail elsewhere. (See "Vaccination for the prevention of shingles (herpes zoster)".)

Poliovirus vaccine — Infants and children with HIV should receive inactivated polio vaccine as recommended for the general population. The small number of adults with HIV at risk of exposure to polio (by travel or work) should receive a primary series IPV if there is no documentation of vaccination status [71]. A single lifetime booster with IPV is recommended for adults at continued risk of exposure to polio although the duration of protection is unknown [71]. (See "Poliovirus vaccination".)

LIVE VACCINES

Rotavirus vaccine — Rotavirus vaccination is not contraindicated in infants with or exposed to HIV and is generally supported by expert groups [3,6]. Dosing and schedule recommendations are the same as for infants without HIV. (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 children with HIV and without evidence of severe immunosuppression (ie, CD4 cell percentage ≥15 percent) [3,6,72]. A detailed discussion of MMR vaccination in children with HIV is discussed elsewhere. (See "Measles, mumps, and rubella immunization in infants, children, and adolescents".)

For older children and adults with newly diagnosed HIV 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) [72]. 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 patients with HIV and severe immunosuppression [3,72]. Additionally, administration of the measles, mumps, rubella, and varicella combination vaccine is not recommended in patients with HIV 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 [73]. 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 patients with HIV and without severe immunosuppression [74,75]. However, the antibody response to MMR vaccine in children and adults with HIV is low, even among those receiving ART [74,76,77], although in one study of children on ART, a second MMR dose improved protective antibody development [78].

The majority of adults with HIV are seropositive to measles, even if the CD4 cell count is <200 cells/microL [76], suggesting that protective antibodies elicited by MMR vaccination prior to HIV infection are not substantially effected by HIV-associated immune decline.

Varicella vaccine

Indications and administration — Varicella vaccine is recommended for children with HIV 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 adults and adolescents with HIV and 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 adults and adolescents with HIV and 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 patients with HIV and 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 patients with HIV as it has not been studied in this population.

Varicella vaccine is administered in two doses given three months apart [5,7]. Eligible children should receive the vaccination as soon as possible after the first birthday.

Postexposure prophylaxis following exposure to varicella-zoster virus is indicated for individuals with HIV 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 children and adults with HIV [5]. Varicella vaccine has been demonstrated to be safe [79], effective [80], and immunogenic in asymptomatic children with HIV and CD4 percentages of 25 percent or more [81-84]. 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) [85]. Regardless of immunologic category, 79 percent of vaccine recipients with HIV 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 and a CD4 count ≥200 cells/microL would have comparable immunity to the children with HIV described above.

In studies in children, varicella vaccination did not affect the CD4 cell percentage or plasma viral level [82,85].

Other risks associated with varicella vaccination are discussed elsewhere. If vaccination results in disease because of vaccine virus, therapy with acyclovir is recommended [5]. (See "Vaccination for the prevention of chickenpox (primary varicella infection)", section on 'Adverse events'.)

Yellow fever vaccine — Yellow fever vaccine can be administered, if indicated, to patients with HIV and CD4 cell counts ≥200 cells/microL [86]. 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 patients with HIV (most of whom had CD4 cell counts ≥200 cells/microL), there were no serious adverse events reported [87].

Although yellow fever vaccine appears to be safe among patients with HIV and without severe immunosuppression, it is less immunogenic than among individuals without HIV [88-90]. 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 patients without HIV [89].

In one prospective study of 240 patients with HIV 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 [91]. There are conflicting data as to whether the level of immunosuppression is associated with vaccine immunogenicity [89,91].

Indications and general risks of the yellow fever vaccine are discussed in detail elsewhere. (See "Yellow fever: Treatment and prevention", section on 'Prevention'.)

BCG vaccine — Bacillus Calmette Guerin (BCG) vaccines are administered to newborn infants in developing countries to reduce the risk of developing tuberculosis. Although patients with HIV are at risk of developing tuberculosis, disseminated BCG has been reported after vaccination [92], with complications occurring up to many years after vaccination [93,94]. Since the efficacy of the vaccine in patients with HIV 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 [95].

Preliminary data from a randomized placebo-controlled trial among 2013 patients with HIV in Tanzania suggest that an inactivated whole cell mycobacterial vaccine (Mycobacterium vaccae) is safe and protects against tuberculosis infection [96].

PASSIVE IMMUNIZATION — Since patients with HIV and 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 immunoprophylaxis' 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'.)

SPECIFIC CIRCUMSTANCES

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 — Pregnant women with HIV 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 patients with HIV" 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 5^th to 6^th 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 10^th to 12^th 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.)

●Basics topics (see "Patient education: Vaccines for adults with HIV (The Basics)" and "Patient education: What you should know about vaccines (The Basics)" and "Patient education: Vaccines for adults (The Basics)")

●Beyond the Basics topic (see "Patient education: Vaccines for adults (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. Patients with HIV 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 persons with HIV compared to those without HIV. Thus, for patients with HIV, 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 children with or exposed to HIV, 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.)

●Adults with HIV 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.)

●Adults with HIV should also receive the COVID-19 vaccine if they are eligible according to local guidelines for vaccine allocation. Although specific data on the efficacy and safety of COVID-19 vaccines in individuals with HIV are limited, the benefits likely outweigh any potential risks in the setting of HIV. (See 'COVID-19 vaccines' above.)

●Human papillomavirus (HPV) vaccine should be given to individuals with HIV 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 'Patients with HIV or immunocompromising conditions'.)

●Adults with HIV 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 adults with HIV".)

●We suggest herpes zoster vaccination with recombinant zoster vaccine (RZV) for all patients with HIV who are 50 years and older (Grade 2B). RZV is administered as two doses, at least eight weeks apart. The live zoster vaccine is a reasonable alternative if RZV cannot be given but is only appropriate for patients with a CD4 cell count ≥200 cells/microL. (See 'Zoster vaccine' above.)

●Adults with HIV 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 adults with HIV".)

●Adults with HIV who are not immune to hepatitis A virus (HAV) should receive the HAV vaccine series. (See 'Hepatitis A vaccine' above.)

●We suggest meningococcal conjugate vaccination (Menactra or Menveo) for all individuals with HIV 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 vaccination in children and adults", section on 'Indications and schedules in the United States'.)

●Although patients with HIV 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 adults with HIV who do not have other specific indications (eg, asplenia). Children with HIV should receive vaccination against H. influenzae type B (Hib) as recommended for the pediatric population without HIV. (See 'Haemophilus influenzae vaccine' above.)

●In general, live vaccines should not be given to individuals with HIV 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. (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 patients with HIV. (See 'BCG vaccine' above.)

ACKNOWLEDGMENT — We are saddened by the death of John G Bartlett, MD, who passed away in January 2021. UpToDate gratefully acknowledges Dr. Bartlett's role as section editor on this topic, his tenure as the founding Editor-in-Chief for UpToDate in Infectious Diseases, and his dedicated and longstanding involvement with the UpToDate program.