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Immunizations
Immunizations and HIV
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Introduction
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Efficacy of Vaccinations in HIV: General Considerations
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Safety of Vaccinations
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transparent imageEffect of Vaccines on HIV Disease Progression
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transparent imageSafety of Live, Attenuated Virus Vaccines in HIV Infection
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Specific Vaccines
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transparent imagePneumococcus
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transparent imageHepatitis B
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transparent imageHepatitis A
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transparent imageInfluenza
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transparent imageHaemophilus influenzae
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transparent imagePolio, Diphtheria, Pertussis, and Tetanus
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transparent imageMeasles, Mumps, Rubella
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transparent imageVaricella and Herpes Zoster
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transparent imageHPV Vaccination in HIV Infection
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Recommended Adult Immunization Schedule, United States
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References
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Introduction
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Vaccination recommendations are determined by weighing the benefits of vaccination against the risks. Although vaccination recommendations for HIV-infected patients are similar to those for HIV-uninfected patients in many respects, HIV can alter the efficacy and safety of vaccines and affect the susceptibility of the patient to the diseases for which immunization can confer protection. Thus, HIV infection impacts both the risks and the benefits of specific vaccinations.

This chapter outlines general considerations about the efficacy and safety of providing various vaccinations for HIV-infected patients, describes what is known about the efficacy and risks of specific vaccines, and summarizes recommendations for routine vaccinations for HIV-infected patients.

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Efficacy of Vaccinations in HIV: General Considerations
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Because HIV infection alters immune function, vaccination of HIV-infected individuals may not confer the same degree of protection gained by immunocompetent persons. A number of studies, which are discussed in detail in relationship to specific vaccines, have demonstrated that immune responses to a variety of vaccines are reduced in patients with HIV infection. Whereas the purpose of administering vaccinations is to prevent clinically important disease, studies that use clinical end points to determine vaccine efficacy are difficult to perform because they require large numbers of persons and lengthy follow-up. Instead, studies of the efficacy of vaccinations in HIV-infected subjects have relied on using a surrogate for clinical end points: the ability to produce antibody responses that are thought to confer immune protection. Although that end point is easier to measure and confers useful information, it has important limitations that diminish the certainty of vaccination recommendations for persons with HIV infection.

Antibody levels that confer protection against various infections are not always sharply defined for immunocompetent individuals. Whether antibody levels associated with immune protection in immunocompetent persons confer the same degree of protection in persons with HIV infection is unknown. It is possible that factors such as impaired cell-mediated immunity may alter the protection offered by specific antibody levels. Antibody responses that fail to achieve levels associated with protection for immunocompetent persons, however, are unlikely to offer protection for persons with HIV. Thus, studies in which HIV-infected persons fail to achieve target antibody levels strongly suggest that vaccination will be ineffective, whereas studies in which target antibody levels are achieved may contribute to an overestimation of the expected benefit of vaccination.

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Safety of Vaccinations
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Effect of Vaccines on HIV Disease Progression
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Activation of the cellular immune system is important in the pathogenesis of HIV disease, and that fact has given rise to concerns that activation of the immune system through vaccinations might accelerate the progression of HIV disease. Activation of CD4 lymphocytes, which takes place when these cells respond to an antigenic stimulus, makes them more susceptible to HIV infection.(1) Activated CD4 cells, once they become infected, support replication of HIV. Resting CD4 cells, although less susceptible, also are vulnerable to HIV infection. Replication of HIV in these cells is restricted, however, until immunologic activation occurs, at which time active HIV replication is initiated. These observations suggest that activation of the immune system through vaccinations could accelerate the progression of HIV disease through enhanced HIV replication.

Studies of influenza vaccination have shown conflicting results in terms of its effect on HIV viral replication and immune activation. Although a number of studies have shown transiently increased levels of HIV RNA and evidence of T-cell activation following influenza vaccination,(2-9) these effects have not been seen in other studies.(8,10-16) No negative impact of influenza vaccine on CD4 cell count or time to AIDS was seen in a retrospective review of 8 years of data on influenza vaccinations from the 1990s.(17) The benefits of appropriate vaccination generally are felt to outweigh the risks of transient viremia. If feasible, it is preferable to have patients on antiretroviral therapy (ART) prior to receipt of vaccination, as that may help blunt or eliminate vaccine-associated viremia and potentially improve immune response to vaccination. However, time-sensitive vaccinations for individuals who are not on ART, such as influenza vaccinations, should not be delayed.

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Safety of Live, Attenuated Virus Vaccines in HIV Infection
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In general, it is preferable to avoid live-virus vaccines if an alternative inactivated vaccine is available, as in the case of influenza. However, many vaccines are available only as live-virus vaccines, and there are concerns about administration of live, attenuated disease-causing organisms to HIV-infected patients with severe immunocompromise. There are several reports of severe illness or death involving HIV-infected individuals after live-virus vaccination. In one case, a military recruit with asymptomatic HIV infection developed severe, disseminated vaccinia after receiving smallpox vaccination.(18) Another patient, who received bacillus Calmette-Guérin (BCG) for tuberculosis vaccination, developed disseminated disease,(19) and there are reports of HIV-infected patients with disseminated BCG infection from vaccination administered many years earlier.(20)

Although data are limited, in general, HIV-infected individuals who are on ART with well-controlled HIV RNA levels and CD4 counts of >200 cells/µL (or ≥15%) may receive indicated live-virus vaccines such as measles, mumps, rubella (MMR) and varicella if lacking immunity; but these vaccines should be avoided in patients with CD4 counts of <200 cells/µL.(21) BCG should not be given to those with severe immunocompromise owing to HIV, and it is not recommended routinely in the United States. The live, attenuated oral polio vaccine (OPV) is not recommended for persons with HIV infection outside resource-limited settings if the inactivated polio vaccine (IPV) is available. Considerations for use of live, attenuated influenza vaccine (LAIV), MMR, varicella, and zoster vaccines in HIV infection are examined in the appropriate sections below.

For persons in whom it is deemed appropriate to give both MMR and varicella vaccines, they can be given simultaneously. If they are not given on the same day, the varicella vaccine should be given at least 28 days after MMR, based on data in children showing that failure rates are higher if given <28 days after MMR vaccination.(22) Live-virus vaccination should be avoided during and 3 months after intravenous immunoglobulin (IVIG) treatment, if possible, because passive antibodies in IVIG may impair response to live-virus vaccination with MMR or varicella for up to 3 months after IVIG infusion.(23)

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Specific Vaccines
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Pneumococcus
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Invasive pneumococcal disease remains a source of significant morbidity and mortality among HIV-infected individuals. Although the availability of ART has decreased the rates of pneumococcal bacteremia, incidence remains 35-fold higher than in age-matched HIV-uninfected persons in the United States.(24,25) Therefore, pneumococcal vaccination is recommended in HIV infection to help reduce invasive pneumococcal disease.

Antibody response to the polysaccharide 23-valent pneumococcal vaccine (PCV) appears to be related to CD4 cell count, with responses diminished at counts of <200 cells/µL in patients on ART (26) and at counts of <500 cells/µL in those not on ART.(27) Vaccination of adults with the protein-conjugated 7-valent PCV does not appear to boost antibody production in HIV infection.(28) Data on the efficacy of vaccination in preventing pneumococcal disease have been inconsistent. A multicenter, case-control study in the United States indicated lower rates of invasive pneumococcal disease after vaccination in patients with CD4 counts of >500 cells/µL but not in those with counts of <500 cells/µL.(29) Conversely, a study from Uganda conducted when ART was not widely available demonstrated an unexpected increase in rates of pneumonia among vaccinated individuals followed by a 16% reduction in mortality.(30) The pneumococcal vaccine generally is recommended in developed settings, whereas more data are awaited for use in sub-Saharan Africa. U.S. HIV guidelines currently recommend that PCV vaccination every 5 years be considered for individuals with CD4 counts of >200 cells/µL.(31)

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Hepatitis B
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The routes of transmission for hepatitis B virus (HBV) are similar to those for HIV. Thus, most patients who have acquired HIV infection are at risk of HBV infection and could benefit from effective HBV vaccination.(32) HIV-seropositive persons have a 3- to 6-fold higher risk of becoming chronic carriers if they become infected with HBV compared with HIV-seronegative controls, which provides an additional rationale for using HBV vaccination in HIV-infected persons.(33,34) HIV-seropositive hepatitis B carriers also are more likely to have high levels of hepatitis B viremia, making them potentially more infective,(35) and they may have more rapidly progressive hepatic disease than HIV-uninfected individuals.(36) These considerations make a powerful public health argument for the importance of HBV vaccination for all individuals with HIV infection, as is recommend by the Advisory Committee on Immunization Practices (ACIP) of the U.S. Centers for Disease Control and Prevention (CDC).(37)

HIV infection is associated with an impaired antibody response to HBV vaccination, with a highly variable response rate of 18-71% in HIV-infected persons vs 60-80% in HIV-uninfected persons.(38) Lower CD4 cell count at time of vaccination also is associated with an impaired response; in one series, CD4 counts of <200 cells/µL were associated with a response rate of 36% vs a rate of 86% in subjects with CD4 counts of >200 cells/µL.(39) A CD4 nadir of <200 cells/µL and ongoing HIV viral replication also independently predict impaired vaccine response.(40) Treatment with ART may be a more important determinant of vaccine responsiveness than CD4 cell count: One study found similar response rates in ART-treated individuals with CD4 counts of >350 cells/µL and <350 cells/µL. However, in individuals not on ART, CD4 counts of >350 cells/µL were associated with twice the vaccine response rate.(41)

Standard vaccination series are given at 0, 1, and 6 months.(31) Although accelerated vaccine schedules currently are not recommended for HIV-infected individuals, a seroconversion rate of >60% at 12 months was demonstrated with a rapid vaccination schedule of 0, 1, and 2 months with double-dose 40 µg HBV vaccine.(42) That may be an attractive schedule for some providers and vaccine recipients. Given the lower antibody response rates in HIV-infected individuals, HBV surface antibody titers should be checked 1 month after the vaccine series is completed to ensure seroconversion.

Strategies for improving antibody response to vaccination include giving a higher dose of HBV vaccine (40 µg rather than 10 µg or 20 µg). In one study of vaccine-naive individuals with CD4 counts of >350 cells/µL, vaccination with 40 µg led to 64% seroconversion vs 40% with 20 µg (p = .008).(43) No difference in outcome between the dosages was seen at CD4 counts of <350 cells/µL. Other studies have not shown improved seroconversion rates with a 40 µg dose in comparison with a 10 µg or 20 µg dose.(39) Some data support the use of adjuvants such as granulocyte-macrophage colony-stimulating factor (GM-CSF) (44) and cytosine-phosphorothioate-guanine (CPG) 7909.(42) However, data are conflicting as to the efficacy of GM-CSF,(45) and these immunostimulatory adjuvants generally are not available in clinical practice.

Revaccination is a common consideration in HIV clinical practice, owing to frequent nonresponse to initial vaccination. Revaccination often results in seroconversion. In a small study series, revaccination with the same 20 µg dose at the same dosing interval led to 78% seroconversion in 9 nonresponders.(46) A higher, 40 µg dose of HBV vaccination led to 50% seroconversion when given to nonresponders at 0, 1, and 2 months, also suggesting that revaccination may lead to seroprotection after initial nonresponse.(47) Similarly, 76% of participants in an Italian study seroconverted after 1 or 2 boosters with a 40 µg dose.(48)

Isolated anti-HBV core antibody positivity frequently creates confusion among HIV providers who are evaluating individuals for vaccination. This positivity may indicate 1) resolved HBV infection with a waned hepatitis B surface antibody (HBsAb) titer; 2) a false-positive test result; or 3) the presence of "occult HBV" (ie, low-level HBV viremia, often intermittent), in the absence of detectable hepatitis B surface antigen (HBsAg). If the individual has resolved HBV infection, a booster with HBV vaccine should lead to an anamnestic response with detectable HBsAg titers. However, several studies have found that the majority of individuals with isolated anti-core antibodies do not respond to a single dose of HBV vaccination and require the full HBV vaccination series for protective antibody development.(49,50) Individuals who do not respond to HBV vaccination may merit HBV DNA testing for occult HBV infection.(51)

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Hepatitis A
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Men who have sex with men (MSM) have a risk of hepatitis A virus (HAV) infection that may be several-fold higher than it is for control populations.(52) Injection drug users also may have an elevated risk of HAV in some geographic areas. HAV vaccination currently is recommended for HAV-susceptible, HIV-infected individuals who are MSM or have chronic liver disease,(31) and it generally has been found to be safe and well tolerated.(53,54) As with other vaccinations, HAV vaccination is less likely to produce protective antibodies for HIV-infected individuals, who have an estimated 64% seroconversion rate after vaccination.(55) A diminished response has been associated with lower CD4 cell count and male sex.(56,57) Although some experts recommend waiting to vaccinate until immune reconstitution on ART has occurred,(53,56) many providers vaccinate all susceptible, HIV-infected patients regardless of current immune status and revaccinate nonresponders when they achieve higher CD4 counts, preferably >500 cells/µL, on ART.(58,59)

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Influenza
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The duration and severity of influenza appear to be increased in HIV-infected persons.(60-64) Although ART may help reduce the risk of severe influenza and influenza-related complications, the reported hospitalization rate secondary to influenza for these individuals nevertheless has exceeded that of the general population.(65,66) In addition, owing to immunocompromise, HIV-infected patients may be at increased risk of bacterial complications of influenza(67); therefore, they theoretically may have increased benefit from vaccination.

As with other vaccines, antibody responses to influenza vaccine in HIV-infected persons tend to be impaired, with more severe impairment in later stages of HIV infection.(68-71) A second dose of seasonal influenza vaccine has not been shown to improve the immune response in those with advanced HIV-related immunosuppression.(72,73) In terms of clinical protection from influenza, vaccination of HIV-infected individuals has been shown to reduce the incidence of laboratory-confirmed influenza in 2 prospective, nonrandomized studies (74,75) and 1 outbreak investigation.(61) A randomized, double-blind, placebo-controlled study of 102 HIV-infected participants found 100% protective efficacy against confirmed influenza by vaccine, compared with saline placebo.(8) Data for response to the H1N1 (swine flu) vaccine among HIV-infected individuals are lacking.

As with administration of other live viruses, use of LAIV generally has been avoided in HIV-infected patients because of concern about prolonged shedding caused by immunocompromise. In a study of asymptomatic, HIV-infected adults with CD4 counts of >200 cells/µL and HIV RNA levels of <10,000 copies/mL, LAIV appeared safe and did not result in prolonged shedding or increases in HIV RNA.(51) However, LAIV may lead to a less-effective antibody response in adults,(76) regardless of HIV status, and trivalent inactivated vaccine (TIV) remains the preferred vaccine for HIV-infected individuals.

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Haemophilus influenzae
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Two population-based studies have shown that invasive Haemophilus influenzae type B (HiB) disease (primarily pneumonia, but defined as positive cultures obtained from a normally sterile site) is more common in association with HIV infection. A study of men in San Francisco found that the annual incidence of invasive HiB was 8.1 per 100,000 HIV-infected men between 20 and 49 years of age, compared with 0.93 per 100,000 for all men in this age range.(77) In that study, HiB was responsible for 33% of invasive H influenzae infections. A population-based study in Atlanta identified 2 cases of invasive HiB in HIV-infected men among an estimated 3,250 HIV-infected adults, yielding an estimated annual incidence of 41 per 100,000 HIV-infected persons.(78)

Although the relative incidence of invasive HiB infections is higher in HIV-infected adults compared with the general population, the absolute rate (0.01% per year) is low. That finding makes the argument for vaccination against HiB much weaker than the arguments for vaccination against infections such as pneumococcus, for which the incidence is approximately 100 times greater. In addition, most Haemophilus infections in HIV-infected adults involve strains against which the vaccine is not protective.(77,79) For these reasons, routine vaccination against HiB is not recommended for HIV-infected adults. However, vaccination may be considered for HIV-infected individuals at higher risk of invasive disease, such as those with splenic dysfunction. Vaccination is recommended for HIV-infected children, as for HIV-uninfected children.

As with other vaccines, antibody production after vaccination with HiB vaccine has been shown to be lower in HIV-infected patients, particularly those with low CD4 cell counts, than in HIV-uninfected individuals.(80) Accordingly, children should be revaccinated with HiB after immune reconstitution.(81) Vaccination appears to be safe and well tolerated by both children and adults, without impact on CD4 cell count or HIV RNA level.(80,82)

HIV-infected persons appear to achieve adequate antibody responses to HiB vaccination. Steinhoff et al found that HiB conjugated vaccine (HBCV) produced titers above 1 mg/mL, the level associated with protection against childhood meningitis, in about 95% of patients with asymptomatic or mildly symptomatic HIV disease.(83) However, it is not certain that the antibody levels that protect against H influenzae meningitis in children are protective against HiB infections such as pneumonia in adults with HIV. In these persons who had not developed a clinical AIDS-defining diagnosis, the conjugated vaccine, which is T-cell dependent, produced better responses than the T-cell-independent, unconjugated vaccine. In contrast, the unconjugated vaccine produced better responses in persons with advanced HIV disease, with a response rate of 92%, compared with an 80% response rate with the HiB conjugated vaccine. This suggests that, if vaccination is given to HIV-infected persons with advanced HIV disease, the unconjugated vaccine should be used, if available.

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Polio, Diphtheria, Pertussis, and Tetanus
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Few data are available about the safety or efficacy of polio, diphtheria, and tetanus vaccines for HIV-infected adults.

Polio: The live, attenuated oral polio vaccine should be avoided because of an increased risk of paralytic polio in immunocompromised vaccine recipients.(84) If a patient requires polio vaccination, clinicians should use the inactivated vaccine to avoid the risks of a live vaccine. The inactivated polio vaccine increases antibody titers in most patients with CD4 counts of >200 cells/µL, but a small number of patients with CD4 counts of <200 cells/µL failed to respond.(85) The CDC recommends use of the inactivated polio vaccine for HIV-infected children.(52,86)

Diphtheria, pertussis, and tetanus: Inactivated vaccines are used for diphtheria, pertussis, and tetanus and thus are unlikely to pose significant risk to patients with HIV infection. Clinicians should administer these vaccines in the same regimens as for HIV-uninfected patients.(52,86)

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Measles, Mumps, Rubella
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Live vaccines are used for MMR and thus may pose risks in immunocompromised patients. In a study of children with HIV infection, however, no severe reactions were documented in 70 HIV-infected children who received MMR vaccines.(87) Moreover, reports suggest that severe disease with pneumonitis is common with measles in HIV-infected children, with a mortality rate of about 30%. One review suggests that vaccination may reduce the mortality rate of measles in HIV-infected children.(88) On that basis, the CDC recommends measles vaccine for all HIV-infected children who are not severely immunosuppressed (with severe immunosuppression defined as a CD4 percentage of <15%) and who lack evidence of measles immunity.(86) As with other vaccines, serologic response may be poor in HIV infection, and children with severe HIV-related immunosuppression should be considered susceptible to measles even if they have received measles vaccine.(80) The ACIP also recommends mumps and rubella vaccines for HIV-infected children.(86)

Few data on the safety or efficacy of measles vaccine in HIV-infected adults are available. There have been case reports of fatal pneumonitis after measles vaccination in severely immunocompromised adults, and response to vaccine appears to be poor.(89) However, no severe adverse reactions have been reported in HIV-infected patients without advanced immunosuppression who received MMR vaccination.(87,90,91) The CDC recommends MMR vaccination for all HIV-infected adults with CD4 counts of >200 cells/µL who lack evidence of measles immunity.(23)

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Varicella and Herpes Zoster
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The varicella zoster virus (VZV) vaccine is a primary vaccination series intended to prevent clinical chickenpox. The herpes zoster (HZ) vaccine is intended for individuals who have had primary varicella infection or vaccination, with the intent of boosting existing immunity to prevent a varicella reactivation as zoster (shingles) and reduce the severity of clinical zoster if it occurs. Zoster vaccination is not a treatment for acute HZ, nor is it a treatment for post-herpetic neuralgia. The dose of the herpes zoster vaccination is approximately 10 times higher than that of the varicella vaccination.(92) The concern with administration of these live, attenuated vaccines is the risk of developing vaccine-associated disease including rash and, rarely, disseminated disease. However, as wild-type varicella and particularly HZ can be frequent, more severe, and associated with increased complications, the benefits of vaccination against VZV and boosting for HZ generally are felt to outweigh the risks in HIV-infected children and adults without severe immunocompromise. To date, there are few reports of complications associated with either vaccine in HIV-infected individuals. However, HIV-infected patients receiving the vaccines should be advised to seek medical evaluation if a rash develops after vaccination, as this may indicate a vaccine-related varicella infection. In addition, patients who develop a rash should be advised to avoid close contact with severely immunocompromised people until the rash resolves, to avoid the risk of transmission.(93)

Antiviral medications such as acyclovir and valacyclovir with activity against herpesviruses may inhibit the efficacy of varicella and zoster vaccination, given that these are live, attenuated vaccines. These medications should be stopped 24 hours prior to vaccination and for 2 weeks after vaccination, if possible.(92)

Varicella vaccine: The varicella vaccine is now recommended as a 2-dose series, with a minimum 3-month interval between the doses. Children with HIV infection are at increased risk of complications from varicella and herpes zoster compared with HIV-uninfected children.(94) Varicella vaccination was safe, well tolerated, and immunogenic in a small study of HIV-infected children without varicella antibody.(95) The varicella vaccine also was safe, well tolerated, and efficacious in children with immunosuppression owing to bone marrow transplantation, which is reassuring for use of the vaccine in other immunocompromised children.(96,97) The ACIP currently recommends primary varicella vaccination for HIV-infected children with CD4 percentages of ≥15%.(93) The combined MMR + VZV vaccine (MMRV) is not recommend for HIV-infected children, as MMRV contains a higher quantity of virus than the VZV vaccine and has not been studied in HIV infection.

The ACIP also currently recommends that adolescent and adult HIV-infected patients without a history of clinical varicella infection (ie, chickenpox or shingles) and lacking varicella antibody should be considered for primary varicella vaccination as long as the patient's CD4 count is >200 cells/µL.(93)

Zoster vaccine: The risk of varicella reactivation as herpes zoster (shingles) is increased in persons over age 50 as well as in those with HIV infection, who have up to a 10-fold higher risk compared with HIV-uninfected persons, even with effective use of ART.(98,99) Vaccination is currently recommended as 1 dose for all adults of age >50,(100) but the ACIP has not made specific recommendations for vaccinating HIV-infected patients for HZ. The ACIP guidelines do not require that adults undergoing zoster vaccination have a documented history of primary varicella or zoster, nor evidence of varicella antibody, before vaccination, but the recommendations are not targeted to HIV-infected individuals specifically. For HIV-infected patients who do not have a history of primary varicella or evidence of antibody protection, it may be advisable to vaccinate using the lower-dose primary varicella vaccination and to avoid the higher dose of live virus in the HZ vaccine. In any case, it is recommended that all adults without varicella immunity be given primary varicella vaccination. Zoster vaccination should be avoided in patients with CD4 counts of <200 cells/µL.

Studies are ongoing to evaluate the safety and efficacy of zoster vaccination in HIV-infected patients with CD4 counts of >200 cells/µL. Until more data are available, zoster vaccination may be considered for selected patients with CD4 counts of >200 cells/µL who are over the age of 50. Data are not available to guide HZ vaccination in HIV-infected patients <50 years of age, although this is a group with an increased risk of zoster that might benefit from HZ vaccination as well.

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HPV Vaccination in HIV Infection
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There is increasing interest in human papillomavirus (HPV) vaccination in HIV-infected persons, given the high burden of HPV infection and growing rates of HPV-related cancers in this population. HPV infection rates are high in persons with HIV infection, with prevalence of 66% in women and up to 90% in MSM, much higher than in HIV-uninfected counterparts.(101,102) HPV-related cancer such anal and cervical cancer occur at increased rates in the HIV-infected population. The risk of anal cancer for patients with HIV infection remains 2-fold higher than for HIV-uninfected patients, despite effective immune reconstitution with ART.(103)

There are 2 currently available FDA-approved HPV vaccines, each containing inactive viruslike particles. The quadrivalent vaccine, Gardasil, contains the genital wart-causing HPV strains 6 and 11 and the cancer-associated strains 16 and 18. In a large study of girls and women aged 9-26, Gardasil prevented 98.8% of genital warts, 98% of cervical precancerous lesions associated with virus strains targeted by the vaccine, and 98% of cervical dysplasia related to these vaccine strains in subjects with no prior HPV infection.(104,105) Efficacy in preventing cervical intraepithelial neoplasia grade 2 (CIN 2) or greater was higher in women without HPV infection (98%) compared with all study participants,(44%) with and without HPV infection. In HIV-uninfected MSM aged 16-26, the vaccine prevented 95% of persistent anal infections with HPV types targeted by the vaccine and 75% of high-grade anal intraepithelial neoplasia owing to these types, in the per-protocol analysis.(106)

The bivalent vaccine, Cervarix, contains only the cancer-associated strains 16 and 18. Cervarix prevented 93% of CIN 2 or greater cervical dysplasia in HIV-uninfected women, and 30% of CIN 2 or greater in the overall population of women, with and without prior HPV. Both vaccines are currently FDA approved for females aged 9-26 for the prevention of cervical and anal intraepithelial neoplasia and cancer and males aged 9-26 for prevention of anal intraepithelial neoplasia and HPV infection. Vaccination before sexual debut is recommended for maximum efficacy, as the protective benefit of the vaccines was greater in persons without prior HPV infection.

The central concern with HPV vaccination of HIV-infected patients is that many of them, particularly in the developed world, are infected with HIV as adults through sexual activity. Therefore, they may have already acquired oncogenic strains of HPV and would stand to benefit less from HPV vaccination. In addition, many may be outside the FDA recommended age window for HPV vaccination. However, many HIV-infected patients may lack infection with one or both oncogenic strains, and therefore gain some protection from vaccination. This is supported by recent studies of HIV-infected women that found HPV 16 infection in 30%, HPV 18 in 12-19%, and infection with both strains in 9%. Similarly, HIV-infected men have HPV 16 infection rates of 50% and HPV 18 rates of 23%.(107-109) HPV infection is not always persistent; however, studies in HIV-uninfected persons indicate that previous HPV infection reduced vaccine efficacy.

Other concerns about HPV vaccination focus on the possibility that HIV infection may be associated with a less-robust immune response to HPV vaccination, as has been seen with other vaccinations. Data are limited for HPV vaccine efficacy in HIV infection. In HIV-infected children aged 7-12, with CD4 percentages of ≥15%, quadrivalent HPV vaccination led to seroconversion with all 4 antigens in >96% of recipients and appeared safe and well tolerated.(110) Long-term follow-up of this cohort is not yet available. Similarly, in 109 HIV-1-infected men aged ≥18 without high-grade anal intraepithelial neoplasia, the quadrivalent HPV vaccine was safe, had no appreciable effects on plasma HIV-1 RNA or CD4 cell counts, and was highly immunogenic, leading to seroconversion rates of ≥95% for each vaccine type.(111) Interestingly, MSM status has been associated with decreased HPV antibody response. In one series, antibody titers in HIV-infected MSM were approximately 40% of those reported in young HIV-infected men with no history of sex with other men, but were similar to those of young HIV-uninfected MSM who reported having sex with other men.(112)

HPV vaccination thus far appears to be safe and immunogenic in the presence of HIV. Administration of the HPV vaccine is not contraindicated in HIV infection in persons aged 9-26 and is reasonable to consider for this age group, as recommended for the HIV-uninfected population. Investigations are ongoing to address whether HPV vaccination will benefit the broad group of HIV-infected patients >26 years of age or possibly only the subset of older patients who are either uninfected or infected with only 1 oncogenic HPV strain.

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Recommended Adult Immunization Schedule, United States
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Recommended adult immunization schedule, by vaccine and age group (PDF)
From the Centers for Disease Control and Prevention's (CDC) Advisory Committee on Immunization Practices (ACIP), the American Academy of Family Physicians (AAFP), the American College of Obstetricians and Gynecologists (ACOG), and the American College of Physicians (ACP).

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