Infectious Diseases in Clinical Practice:
Routine Vaccination in HIV-Infected Adults
Landrum, Michael L. MD; Dolan, Matthew J. MD
Infectious Disease Service, San Antonio Military Medical Center, Fort Sam Houston, TX; and The Infectious Disease Clinical Research Program, Bethesda, MD.
Support for this work was provided by the Infectious Disease Clinical Research Program (IDCRP) of the Uniformed Services University of the Health Sciences (USUHS), of which the Tri-Service AIDS Clinical Consortium (TACC) is a component. The IDCRP is a DoD tri-service program executed through USUHS and the Henry M. Jackson Foundation for the Advancement of Military Medicine (HJF), in collaboration with United States Department of Health and Human Services/National Institutes of Health/National Institute of Allergy and Infectious Diseases/Division of Clinical Research through Interagency Agreement HU0001-05-2-0011. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official, or as reflecting the views of the Departments of the Army, Navy, Air Force, or the Department of Defense. The authors have no commercial or other association that might pose a conflict of interest.
Address correspondence to Michael L. Landrum, MD, 3851 Roger Brooke Dr, MCHE-MDI, Fort Sam Houston, TX 78234-6200. E-mail: firstname.lastname@example.org.
With improved survival of adult patients with HIV-infection, providing routine immunizations as a part of chronic disease management is an increasingly important issue for clinicians. Unfortunately, although the burdens of vaccine preventable diseases, such as hepatitis B and pneumococcal disease, are substantial for this patient population, currently available data show that most routine vaccinations are not administered to the majority of patients at risk despite widespread availability. Therefore, this review will discuss for clinicians the data regarding the safety, immunogenicity, and clinical efficacy of vaccines in adults infected with HIV, to make an evidence-based case for increased vaccine utilization in the care of HIV-infected patients.
As patients live longer with HIV infection due to highly active antiretroviral therapy (HAART), the health problems encountered during the course of disease are changing from predominantly treatment and prevention of opportunistic diseases to prevention and treatment of long-term comorbidities, such as viral hepatitis and drug-induced dyslipidemia. These changes in the chronic care of patients living with HIV were addressed by recent guidelines from the Infectious Diseases Society of America, one aspect of which was providing routine vaccination for commonly encountered diseases.1
Unfortunately, despite widespread agreement on the potential benefits of vaccination, evidence suggests that vaccination coverage is typically poor. For example, the coverage rates for hepatitis B vaccine and pneumococcal vaccine have been reported to be 32% and 38%, respectively.2,3 The reasons for this are not entirely known but likely involve concerns regarding cost, lack of need, reduced efficacy, or fear of causing harm.2 This review will discuss for clinicians the currently recommended routine vaccines for HIV-infected patients, as well as summarize the evidence supporting those recommendations focusing primarily on the 2 most commonly indicated vaccines, hepatitis B and pneumococcal vaccines.
Although typical vaccine related adverse events do not appear to occur more commonly in HIV-infected adults compared with the general population,4-10 several studies have investigated the effects of vaccination with pneumococcal,11-14 hepatitis B,15 influenza,16-27 and tetanus toxoid28 vaccines upon HIV disease progression, specifically viral replication and CD4 count. The majority of these involved influenza vaccine, with some reporting increased levels of viral replication after vaccination16,17,21,24,26,27 and others reporting no effect.18-20,22,23,25 Most authors agree that if elevations are seen, they occur early after vaccination, are transient, and unlikely to affect disease progression. Possible explanations for the different outcomes include timing of sample collection after vaccination, utilization of different HIV RNA testing methods, and differences in study design and patient populations. However, increases in viral load after vaccination with influenza and other vaccines before the advent of HAART caused some to debate the risks and benefits of widespread vaccination.29 One large observational study including patients from 1990 to 1998 did not find an association between influenza vaccination and progression to AIDS.30 Unfortunately, data regarding viremia after pneumococcal vaccine12-14 or influenza vaccine17,18,22,24 in subjects receiving HAART are somewhat limited. In these studies, no increase in viremia after pneumococcal vaccine was detected, but small, transient elevations were seen after influenza vaccination in 2 uncontrolled studies.17,24 In one of these, Kolber et al24 investigated the occurrence of novel drug resistance mutations among 34 patients on stable HAART regimens with undetectable viral loads at the time of influenza vaccination. One patient developed previously unidentified zidovudine mutations despite excellent medication compliance, and another patient failed therapy after vaccination, but without comparison to controls, conclusions from this study remain limited. Although more data are needed to definitively address the impact of vaccines upon HIV disease course, current data suggest that if risk exists, it is small and likely outweighed by the benefits of providing these vaccines to this patient population.
In addition to the concerns of immune stimulation and disease progression, the safety of administering live vaccines to HIV-infected patients remains incompletely understood. Several anecdotal reports of vaccine-related disease after immunization have been reported in HIV patients with profound immunosuppression. Fatal vaccine-associated pneumonitis was reported in a 21-year-old male patient with AIDS and an undetectable CD4 count after measles-mumps-rubella (MMR) vaccination,31 and at least 9 cases of disseminated BCG, 7 of which were fatal, have also been reported after vaccination in children and adults with AIDS.32,33 In addition, 1 case of disseminated vaccine strain varicella in a 16-month-old boy34 and 1 case of disseminated vaccinia in a military recruit have been reported.35 In both cases, undiagnosed HIV infection was responsible for advanced immunosuppression at the time of immunization.
Although these anecdotal reports are troubling, other investigators have safely given live attenuated viral vaccines to HIV-infected adults. Published reports include the administration of cold-adapted influenza vaccine to HIV-infected adults with CD4 count >200 cells/μL,9 yellow fever vaccine to HIV-infected travelers with CD4 >200 cells/μL,36,37 and MMR to a total of 45 HIV-infected adults with CD4 counts ranging from 140 to 600 cells/μL.38,39 One study also reported no serious adverse events after the inadvertent administration of smallpox vaccine to 10 HIV-infected patients with CD4 counts ranging from 286 to 751 cells/μL.40 However, many of these live vaccine recipients were seropositive for the respective vaccine agent at baseline.9,39,40 No study of varicella vaccination in adults has been published to date, but studies in children have found the vaccine to be well tolerated.41-43 Although the published data are somewhat limited, they suggest that live vaccines may be safely administered to a select portion of patients with HIV, those with CD4 counts >200 cells/μL. However, given the small numbers of reported live vaccine recipients, the potential for harm, and lack of demonstrated efficacy, the only live vaccine recommended for HIV-infected adults is MMR, which should not be administered to patients with advanced immunosuppression.44 Lastly, although smallpox vaccine is not currently indicated, administration could potentially be recommended in certain situations such as a bioterrorism attack. The reader is referred to guidelines for specific recommendations but will need to weigh the relatively well-characterized potential for vaccine risk against the scenario-specific risk for infection and death given the characteristics of an attack (ie, whether the patient was primarily exposed, the scope of the attack, and the success of initial containment effort).45,46
HEPATITIS B VACCINE
Due to shared modes of transmission, the burden of hepatitis B virus (HBV) infection among patients with HIV is large, with up to 50% of adult HIV patients with positive serologic markers for hepatitis B and an estimated 7% with chronic hepatitis B.47-50 Although the impact of HBV infection upon the course of HIV disease and response to HAART is debated,51,52 several studies have shown persistence of HBsAg, increased levels of HBV DNA, prevalence of cirrhosis, prevalence of chronic hepatitis, and liver-related mortality among HBV/HIV coinfected patients compared with patients infected with HBV alone.53-57 In addition, risk of antiretroviral-associated hepatic toxicity seems to be increased compared with HIV-positive, HBV-negative patients.58-63 Because of these reasons, hepatitis B vaccine has been recommended for all HIV-infected patients without prior evidence of HBV infection (Table 1).44,64-66
Several studies have investigated the serologic response to hepatitis B vaccine in HIV-infected patients, all finding low rates of response. One of the first studies compared antibody response to 3 standard doses (20 μg each) of vaccine among men who have sex with men with and without HIV infection and found that nonresponse occurred in 7 of 16 HIV-seropositive patients, compared with only 6 of 68 HIV-seronegative patients.67 Since that time, other investigations have described initial response rates varying from 17% to 55% with 3 standard doses of vaccine administered over 6 months.2,6,68-74 Risk factors for nonresponse have not always been consistent among studies but have included detectable HIV RNA load at the time of vaccination68 and nadir CD4 count before vaccination.2,74 Although retrospective analyses have not found an association between CD4 count at the time of vaccination and nonresponse,2,68,74 one recent prospective study of 192 patients did find higher response rates in patients with CD4 cell counts ≥350 cells/μL (adjusted odds ratio: 2.86, 95% confidence interval (CI): 1.42-5.75, P = 0.002).6 The impact of concurrent administration of HAART upon vaccine response rates has not been thoroughly investigated, but one study found that among vaccinees receiving HAART, the median duration of treatment for responders was 13.5 months, compared with 3.7 months for nonresponders, P = 0.005.68 Lastly, genetic determinants including human leukocyte antigen and cytokine gene polymorphisms have been associated with response to vaccination among HIV patients.75
In addition to poor initial seroresponse rates, protection may be further reduced by waning antibody levels. One study of 78 hemophiliac patients, 11 of which were also HIV-positive, followed subjects for 4 years after initial vaccination. Anti-HBs levels remained protective after 4 years for all HIV-negative patients, whereas levels waned below protection in 5 of 11 HIV-positive patients.76 More recently, Cooper et al5 found that the percentage of patients with protective anti-HBs decreased from 90% immediately after vaccination to 63% after 12 months despite all patients being on HAART and having suppressed HIV RNA.
Several methods at improving seroresponse rates in HIV-infected patients have been attempted. One method, recommended by the Advisory Committee on Immunization Practices for HIV patients, is administering a double dose of the vaccine (Table 1).65,66 Studied previously in dialysis patients,65 one study of HIV patients recently described a nonstatistically significant increase in overall response rate using 40 μg doses of vaccine compared with 20 μg doses (47% vs 34%, P = 0.07).6 However, among patients with CD4 ≥350 cells/μL, response rates were 64% and 39% for double dose and standard dose, respectively (P = 0.008). Likewise, significantly increased response rates were found among patients with HIV RNA loads <10,000 copies/mL (58% vs 37%, P = 0.01).
One additional promising method studied recently in HIV-infected patients but not currently available clinically is the addition of an adjuvant consisting of cytosine and guanine nucleotides linked by phosphate bonds (CpG) to HBV vaccine.5,77 CpG oligodeoxynucleotides are short motifs of bacterial DNA that interact with Toll-like receptor 9 resulting in activation of a broad array of innate immune responses.78 Through modifications to their end components, the type of immune response elicited can be modified. Addition of one such motif, CpG 7909, to hepatitis B vaccine was studied in HIV-positive patients with viral suppression on HAART and resulted in significantly increased levels of anti-HBs for up to 1 year after vaccination, without reducing safety.5 In this study, seroprotective titers at 1 year were found in 100% of subjects that had received CpG in addition to HBV vaccine compared with 63% of subjects that had received vaccine alone, P = 0.008.
Unfortunately, there are only limited data in HIV-infected patients establishing an anti-HBs level ≥10 IU/L as a correlate of protection and regarding clinical efficacy. Hadler et al79 reported long-term immunogenicity and efficacy of plasma-derived HBV vaccine among men who have sex with men and subsequently characterized clinical outcomes for the 340 subjects who developed breakthrough HBV infection.80,81 Of those participants, 64 were determined to be HIV-infected before HBV infection using banked specimens. Interestingly, although all patients developed breakthrough infection, the only group of HIV-infected patients protected from developing chronic hepatitis was the group that had an initial anti-HBs ≥10 IU/L after 3 doses of vaccine. Those receiving an incomplete vaccination series or with nonresponse had equal or higher rates of chronic HBV infection compared with placebo. The study also described worse clinical outcomes in vaccinated HIV-positive individuals with breakthrough HBV infection, as 33% developed chronic infection compared with only 5.9% of HIV-negative vaccine failures (P < 0.001). More recently, a large cohort study of more than 16,000 HIV patients reported that receipt of one or more doses of HBV vaccine was independently associated with reduced incidence of acute HBV infection (odds ratio: 0.6, 95% CI: 0.4-0.9), but no data on seroresponse were reported.47 Lastly, we recently described in our cohort that anti-HBs ≥10 IU/L measured 6 months after the last vaccine dose was significantly associated with prevention of hepatitis B infection over a median of 8 years of follow-up.82 During this time, not one case of chronic hepatitis B occurred among vaccine recipients with anti-HBs ≥10 IU/L after immunization.
Although encouraging, the above data taken collectively suggest that although vaccination seems beneficial for some, a large portion of HIV patients remain unprotected due to either failure to administer the vaccine or a lack of a response. All HIV-infected adults without evidence of hepatitis B infection should be vaccinated, and efforts are needed to improve physician and patient education regarding the need for and benefits of HBV vaccine. The currently recommended dose and schedule are 40 μg at 0, 1, and 6 months.66 Anti-HBs should be measured after completion of the series, and up to 3 additional doses of vaccine should be given to those with anti-HBs <10 IU/L.66 The need for routinely obtaining anti-HBs titers and providing booster doses of vaccine is not clear. Some authorities recommend this approach,56 but to our knowledge, not one case of chronic hepatitis B has been reported in patients achieving anti-HBs ≥10 IU/L after vaccination. Therefore, we do not routinely follow anti-HBs titers or provide booster doses to those with anti-HBs ≥10 IU/L after vaccination. Further studies are needed to clarify many issues including barriers to vaccine administration, methods to improve immunogenicity and maintain long-term protection, vaccine efficacy, determination of clinical correlates of protection, and the need for booster doses of vaccine.
Similar to HBV coinfection, the burden of pneumococcal disease in HIV-infected patients is substantial, despite the advent of HAART.83,84 Although some studies have found a reduction in the incidence of invasive disease since the introduction of HAART,83-85 one recent study did not.86 The estimated incidence in HIV-infected adults remains approximately 500 cases/100,000 person-years (PY), approximately 30-fold higher than in non-HIV-infected adults.83,84,86-88 Streptococcus pneumoniae isolates covered by the currently available 23-valent polysaccharide vaccine (PPV) account for approximately 80% to 94% of cases in adults, whereas only 40% to 56% of isolates would be covered by the currently licensed 7-valent conjugate vaccine (PCV).87-90 In addition, the mortality rate of invasive disease may be increasing from 8% in the pre-HAART era to 21% to 26% in the era of HAART.84,89,91 For these reasons, vaccination with PPV is recommended for all HIV-infected adults after diagnosis, and revaccination should be considered when it has been >5 years since previous immunization or after immune reconstitution if the CD4 count was <200 cells/μL at the time of the initial vaccination.44,64,92 Unfortunately, as for hepatitis B vaccine, the data supporting these recommendations are limited.
Several studies have investigated serologic responses to PPV, describing low response rates in patients infected with HIV.8,12-14,93-101 Factors predictive of a good or poor response remain largely unknown. In general, responses seem best when the vaccine is administered early in the course of disease,13,97 and whereas some prospective studies have shown higher CD4 counts at the time of vaccination to be associated with improved responses,97-99 others have not.12,93,96 In addition, one early investigation found that zidovudine monotherapy improved responses,94 but more recent studies have found no improvement in vaccine response in patients receiving monotherapy96 or HAART,93,97 supporting the assumption that pneumococcal polysaccharides are T-cell-independent antigens. Similar to hepatitis B vaccine, the duration of response is reduced in HIV-infected patients compared with otherwise healthy controls.96,99 Limited data also show that a second sequential dose of PPV does not improve antibody levels in those without an initial response.102 Lastly, whereas revaccination is recommended,64 antibody responses to revaccination ≥5 years after initial immunization are significantly lower in frequency and magnitude compared with responses seen in newly HIV-infected subjects.13
Studies evaluating antibody responses to PCV in HIV-infected patients have also been disappointing. Ahmed et al8 compared polysaccharide and conjugate vaccine responses in HIV-infected patients and healthy controls. Pneumococcal conjugate vaccine was found to elicit significantly higher IgG antibody titers than PPV in healthy subjects, but responses to the 2 vaccines were similar in HIV-infected patients.8 Two studies have investigated antibody responses after giving sequential combinations of PPV and PCV in the following sequences: PCV-PCV, PCV-PPV, and PCV-PCV-PPV.7,14 Unfortunately, despite the various vaccination strategies attempted with PCV, none conclusively demonstrated improved immunogenicity compared with PPV alone. The T-cell-dependent manner in which PCV elicits an improved vaccine response in healthy individuals may contribute to the failure of PCV to consistently provoke a more robust response than PPV in HIV-infected patients. Although responses to PCV do correlate with CD4 count,7,8 aberrant T-cell function even in those with CD4 count >500 cells/μL seems to be sufficient to impair immunogenicity. The effect of HAART upon antibody responses after PCV remains to be determined.
Data regarding clinical efficacy are somewhat limited with only one prospective trial, and results have been mixed.3,86,91,103-105 In case-control studies, Gebo et al104 found that the use of PPV in patients with CD4 count >200 cells/μL was associated with a reduced risk of pneumococcal disease (adjusted odds ratio: 0.22, 95% CI: 0.05-0.98), and Breiman et al103 found an overall vaccine efficacy of 49% (95% CI: 12-70, P = 0.02). Of note in this latter study, the only subgroup with a statistically significant level of protection was white patients, and there was no difference in efficacy when stratified by CD4 count. The strongest evidence supporting the use of PPV was a large cohort investigation of more than 39,000 patients with nearly 71,000 PY of observation, which showed that vaccination was independently associated with a reduction in the incidence of pneumococcal disease from 9.3/1000 PY to 2.6/1000 PY (relative risk: 0.5, 95% CI: 0.3-0.9, P = 0.02) only for patients with CD4 count ≥500 cells/μL at the time of vaccination.3 However, more recent observational investigations have found no protective effect from PPV administration.86,106
Even more troubling are data from the only randomized, double-blinded, placebo-controlled trial regarding PPV in HIV-infected patients, done in Uganda. Including nearly 1400 randomized patients, over half of which were WHO stage 3, the study found a trend toward increased rates of invasive disease among vaccinees and an increased risk of all-cause pneumonia within the first 6 months in those receiving PPV (hazard ratio: 2.82, 95% CI: 1.19-6.66).105 Although generalizations to other populations are difficult and limited by many factors including the advanced stage of disease of patients and the lack of ART use, the results are still concerning. The authors hypothesized that the vaccine had resulted in some deleterious effect upon antipneumococcal immunity. However, in a follow-up study comparing 31 case patients with 124 controls, this was not the case, and the investigators found significant relationships between lower antipneumococcal polysaccharide IgG concentrations, lower opsonophagocytic killing, and case status.107
Considering the data together, it is clear that many questions regarding pneumococcal vaccination in HIV patients remain, including clinical efficacy. Because of the perceived risk-benefit ratio and low cost, vaccination remains recommended despite the lack of clear evidence supporting its use. By our estimation, a prospective randomized trial in the United States would require approximately 20,000 PY of follow-up to show that the vaccine was 60% efficacious in preventing invasive disease with 80% power. Without such data, decisions regarding the use of PPV will continue to be based on surrogate end points. More research is needed concerning improving immunogenicity and clinical efficacy, as well as clinical correlates of protection, such as opsonophagocytic activity107,108 and other qualitative differences in antibody function.109
Although data regarding the natural history and severity of influenza in HIV-infected patients remain limited,110,111 annual influenza vaccination with inactivated vaccine is recommended.44,64,112 Similar to other vaccines, serologic responses to inactivated influenza vaccine are lower compared to healthy controls.10,22,23 Higher CD4 cell count and lower HIV RNA level at the time of vaccination have both been independently correlated with improved antibody response to vaccine.10,16,20,23 In addition, one study described a direct correlation with increased viral load after vaccination and antibody response.27 However, unlike healthy controls, successive annual vaccination was not found to improve postvaccination antibody titers in HIV patients not receiving HAART.10
Studies investigating the efficacy of inactivated influenza vaccine in HIV-infected adults have been conducted and were the subject of a recent meta-analysis.111 Fine et al111 described an influenza outbreak in a metropolitan AIDS residential facility and found a statistically insignificant reduction of 27% of influenza-like illness (ILI) among AIDS patients. However, vaccination was associated with a significant reduction of ILI among AIDS patients with either CD4 cell count >100 cells/μL or HIV RNA load <30,000 copies/mL. A more recent, prospective nonrandomized investigation of 626 patients reported a vaccine efficacy of 71% in preventing laboratory-confirmed ILI. Efficacy was no different regardless of HAART use, but too few patients with CD4 counts <200 cells/μL were included in the study to evaluate efficacy in those with advanced immunosuppression.114 One small prospective randomized, double-blind trial of 102 patients before the advent of HAART found a vaccine efficacy of 93% in preventing culture or serologically confirmed ILI.115 However, mean CD4 count for all participants was approximately 400 cells/μL, making generalizations to patients with more advanced disease difficult. Nonetheless, the current data suggest that influenza vaccine seems to be as effective in HIV-infected adults as it is in otherwise, healthy adults.
Other recommended vaccines include tetanus/diphtheria/pertussis (Td/Tdap), hepatitis A, MMR, and meningococcal vaccine.44 Both hepatitis A and meningococcal vaccines are recommended only if an additional medical, occupational, or lifestyle risk factor is present. There are no data regarding clinical efficacy of any of these vaccines specifically in patients with HIV. Serologic responses to tetanus and diphtheria toxoid were 83% to 100% and 61% to 73%, respectively, with response rates to both antigens directly related to CD4 counts.116 Hepatitis A vaccine has been found to induce seroresponse rates in 48% to 94% of recipients without inducing changes in HIV RNA load or CD4 count.4,117-119 Improved responses are seen in those with higher CD4 count, and at least one study described waning antibody responses at 1 year for patients with CD4 counts <300 cells/μL at the time of vaccination.120 No data regarding combination hepatitis A/hepatitis B vaccine (Twinrix) have been reported. Lastly, of the 9 measles seronegative HIV-infected adults reported to have received measles vaccine, only 2 had a positive serologic response after vaccination.38,39
Finally, although not currently recommended for patients with HIV infection, a quadrivalent human papillomavirus (HPV) vaccine (HPV types 6, 11, 16, 18) was recently approved for use by the Food and Drug Administration and recommended for use in adolescent females.121-123 The vaccine has yet to be studied in HIV-infected patients. Estimates of HPV prevalence in HIV-infected individuals range from 63% to 93% with vaccine-specific HPV types accounting for a significant proportion of infection.124-128 With such high prevalence rates, it is unclear how many HIV-infected patients would be candidates for the vaccine, especially when considering that the vaccine did not demonstrate efficacy in those with evidence of infection with vaccine HPV types at baseline.121 In addition to this concern, another study found that immunogenicity was reduced in young women aged 16 to 23 years compared with adolescent males and females aged 10 to 15 years.129 Human papillomavirus vaccine is a recombinant peptide similar to hepatitis B vaccine, so similar seroresponse rates and risk factors for poor response might be anticipated. However, given the concerns listed above, it is not clear whether the vaccine will significantly impact HPV-associated disease in the HIV-infected population outside the benefit achieved through universal adolescent immunization.
Despite recommendations for use of many routine vaccinations in HIV-infected adults, data suggest that the use of vaccines is poor. Although response to these immunizations may in some cases be less than that seen in otherwise healthy adults, large subsets of HIV-infected adults who would benefit from vaccination remain at risk. Therefore, the use of these vaccines, particularly HBV vaccine, represents an excellent target for the improvement of care. Research goals for the long-term include improving immunogenicity for the currently available vaccines, clarifying the role of HAART in improving vaccine response, and the study of newly available vaccines, such as HPV vaccine.
1. Aberg JA, Gallant JE, Anderson J,. Primary care guidelines for the management of persons infected with human immunodeficiency virus: recommendations of the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis
2. Tedaldi EM, Baker RK, Moorman AC,. Hepatitis A and B vaccination practices for ambulatory patients infected with HIV. Clin Infect Dis
3. Dworkin MS, Ward JW, Hanson DL, et al. Pneumococcal disease among human immunodeficiency virus-infected persons: incidence, risk factors, and impact of vaccination. Clin Infect Dis
4. Shire NJ, Welge JA, Sherman KE. Efficacy of inactivated hepatitis A vaccine in HIV-infected patients: a hierarchical Bayesian meta-analysis. Vaccine
5. Cooper CL, Davis HL, Angel JB,. CPG 7909 adjuvant improves hepatitis B virus vaccine seroprotection in antiretroviral-treated HIV-infected adults. AIDS
6. Fonseca MO, Pang LW, Cavalheiro N,. Randomized trial of recombinant hepatitis B vaccine in HIV-infected adult patients comparing a standard to a double dose. Vaccine
7. Kroon FP, van Dissel JT, Ravensbergen E,. Enhanced antibody response to pneumococcal polysaccharide vaccine after prior immunization with conjugate pneumococcal vaccine in HIV-infected adults. Vaccine
8. Ahmed F, Steinhoff MC, Rodriguez-Barradas MC,. Effect of human immunodeficiency virus type 1 infection on the antibody response to a glycoprotein conjugate pneumococcal vaccine: results from a randomized trial. J Infect Dis
9. King JC Jr, Treanor J, Fast PE,. Comparison of the safety, vaccine virus shedding, and immunogenicity of influenza virus vaccine, trivalent, types A and B, live cold-adapted, administered to human immunodeficiency virus (HIV)-infected and non-HIV-infected adults. J Infect Dis
10. Kroon FP, van Dissel JT, de Jong JC,. Antibody response after influenza vaccination in HIV-infected individuals: a consecutive 3-year study. Vaccine
11. Brichacek B, Swindells S, Janoff EN,. Increased plasma human immunodeficiency virus type 1 burden following antigenic challenge with pneumococcal vaccine. J Infect Dis
12. Amendola A, Tanzi E, Zappa A,. Safety and immunogenicity of 23-valent pneumococcal polysaccharide vaccine in HIV-1 infected former drug users. Vaccine
13. Tasker SA, Wallace MR, Rubins JB,. Reimmunization with 23-valent pneumococcal vaccine for patients infected with human immunodeficiency virus type 1: clinical, immunologic, and virologic responses. Clin Infect Dis
14. Feikin DR, Elie CM, Goetz MB,. Randomized trial of the quantitative and functional antibody responses to a 7-valent pneumococcal conjugate vaccine and/or 23-valent polysaccharide vaccine among HIV-infected adults. Vaccine
15. Cheeseman SH, Davaro RE, Ellison RT. Hepatitis B vaccination and plasma HIV-1 RNA. N Engl J Med
16. Fuller JD, Craven DE, Steger KA,. Influenza vaccination of human immunodeficiency virus (HIV)-infected adults: impact on plasma levels of HIV type 1 RNA and determinants of antibody response. Clin Infect Dis
17. Gunthard HF, Wong JK, Spina CA,. Effect of influenza vaccination on viral replication and immune response in persons infected with human immunodeficiency virus receiving potent antiretroviral therapy. Clin Infect Dis
18. Macias J, Pineda JA, Leal M,. HIV-1 plasma viremia not increased in patients receiving highly active antiretroviral therapy after influenza vaccination. Eur J Clin Microbiol Infect Dis
19. Glesby MJ, Hoover DR, Farzadegan H,. The effect of influenza vaccination on human immunodeficiency virus type 1 load: a randomized, double-blind, placebo-controlled study. J Infect Dis
20. Fowke KR, D'Amico R, Chernoff DN,. Immunologic and virologic evaluation after influenza vaccination of HIV-1-infected patients. AIDS
21. Tasker SA, O'Brien WA, Treanor JJ,. Effects of influenza vaccination in HIV-infected adults: a double-blind, placebo-controlled trial. Vaccine
22. Amendola A, Boschini A, Colzani D,. Influenza vaccination of HIV-1-positive and HIV-1-negative former intravenous drug users. J Med Virol
23. Malaspina A, Moir S, Orsega SM,. Compromised B cell responses to influenza vaccination in HIV-infected individuals. J Infect Dis
24. Kolber MA, Gabr AH, De La Rosa A,. Genotypic analysis of plasma HIV-1 RNA after influenza vaccination of patients with previously undetectable viral loads. AIDS
25. Pinto LA, Blazevic V, Anderson SA,. Influenza virus-stimulated generation of anti-human immunodeficiency virus (HIV) activity after influenza vaccination in HIV-infected individuals and healthy control subjects. J Infect Dis
26. O'Brien WA, Grovit-Ferbas K, Namazi A,. Human immunodeficiency virus type 1 replication can be increased in peripheral blood of seropositive patients after influenza vaccination. Blood
27. Staprans SI, Hamilton BL, Follansbee SE,. Activation of virus replication after vaccination of HIV-1-infected individuals. J Exp Med
28. Stanley SK, OstrowskiMA, Justement JS,. Effect of immunization with a common recall antigen on viral expression in patients infected with human immunodeficiency virus type 1. N Engl J Med
29. Crouch RB. Editorial response: influenza, influenza virus vaccine, and human immunodeficiency virus infection. Clin Infect Dis
30. Sullivan PS, Hanson DL, Dworkin MS,. Effect of influenza vaccination on disease progression among HIV-infected persons. AIDS
31. Angel JB, Walpita P, Lerch RA,. Vaccine-associated measles pneumonitis in an adult with AIDS. Ann Intern Med
32. Talbot EA, Perkins MD, Silva SFM,. Disseminated bacille Calmette-Guerin disease after vaccination: case report and review. Clin Infect Dis
33. Edwards KM, Kernodle DS. Possible hazards of routine Bacillus Calmette-Guerin immunization with human immunodeficiency virus infected children. Pediatr Infect Dis J
34. Kramer JM, LaRussa P, Tsai WC,. Disseminated vaccine strain varicella as the acquired immunodeficiency syndrome-defining illness in a previously undiagnosed child. Pediatrics
35. Redfield RR, Wright DG, James WD,. Disseminated vaccinia in a military recruit with human immunodeficiency virus (HIV) disease. N Engl J Med
36. Receveur MC, Thiebaut R, Vedy S,. Yellow fever vaccination of human immunodeficiency virus-infected patients: report of two cases. Clin Infect Dis
37. Goujon C, Tohr M, Feuillie V, et al. Good tolerance and efficacy of yellow fever vaccine among subject carriers of human immunodeficiency virus. Program and abstracts of the 4th International Conference on Travel Medicine. Geneva, Switzerland: International Society of Travel Medicine/World Health Organization; 1995:63.
38. Wallace MR, Hooper DG, Graves SJ,. Measles seroprevalence and vaccine response in HIV-infected adults. Vaccine
39. Sprauer MA, Markowitz LE, Nicholson JK,. Response of human immunodeficiency virus-infected adults to measles-rubella vaccination. J Acquir Immune Defic Syndr
40. Tasker SA, Schnepf GA, Lim M,. Unintended smallpox vaccination of HIV-1-infected individuals in the United States military. Clin Infect Dis
41. Armenian SH, Han JY, Dunaway TM,. Safety and immunogenicity of live varicella virus vaccine in children with human immunodeficiency virus type 1. Pediatr Infect Dis J
42. Levin MJ, Gershon AA, Weinberg A,. Immunization of HIV-infected children with varicella vaccine. J Pediatr
43. Levin MJ, Gershon AA, Weinberg A,. Administration of live varicella vaccine to HIV-infected children with current or past significant depression of CD4+ T cells. J Infect Dis
44. Centers for Disease Control and Prevention. Recommended adult immunization schedule: United States, October 2006-September 2007. MMWR
45. Centers for Disease Control and Prevention. Vaccinia (smallpox) vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2001. MMWR
46. Centers for Disease Control and Prevention. Recommendations for using smallpox vaccine in a pre-event vaccination program: supplemental recommendations of the Advisory Committee on Immunization Practices (ACIP) and the Healthcare Infection Control Practices Advisory Committee (HICPAC). MMWR
47. Kellerman SE, Hanson DL, McNaghten AD,. Prevalence of chronic hepatitis B and incidence of acute hepatitis B infection in human immunodeficiency virus-infected subjects. J Infect Dis
48. Shire NJ, Rouster SD, Rajicic N,. Occult hepatitis B in HIV-infected patients. J Acquir Immune Defic Syndr
49. Thomas DL, Cannon RO, Shapiro CN,. Hepatitis C, hepatitis B, and human immunodeficiency virus infections among non-intravenous drug-using patients attending clinics for sexually transmitted diseases. J Infect Dis
50. Tien PC, Kovacs A, Bacchetti P,. Association between syphilis, antibodies to herpes simplex virus type 2, and recreational drug use and hepatitis B virus infection in the women's interagency HIV study. Clin Infect Dis
51. Sinicco A, Raiteri R, Sciandra M. Co-infected and super-infection of hepatitis B virus in patients infected with HIV: no evidence of faster progression to AIDS. Scand J Infect Dis
52. Sheng W, Chen M, Hsieh S, et al. Impact of chronic hepatitis B virus infection on outcomes of patients infected with HIV in an area where HBV infection is hyperendemic. Clin Infect Dis
53. Colin JF, Cazals-Hatem D, Loriot MA, et al. Influence of human immunodeficiency virus infection on chronic hepatitis B in homosexual men. Hepatology
54. Thio CL, Seaberg EC, Skolasky R, et al. HIV-1, hepatitis B virus, and risk of liver-related mortality in the Multicenter Cohort Study (MACS). Lancet
55. Thio CL. Hepatitis B in the human immunodeficiency virus-infected patient: epidemiology, natural history, and treatment. Semin Liver Dis
56. Soriano V, Puoti M, Bonacini M, et al. Care of patients with chronic hepatitis B and HIV co-infection: recommendations from an HIV-HBV international panel. AIDS
57. Gilson RJC, Hawkins AE, Beecham MR, et al. Interactions between HIV and hepatitis B virus in homosexual men: effects on the natural history of infection. AIDS
58. Aceti A, Pasquazzi C, Zechini B, et al. Hepatotoxicity development during antiretroviral therapy containing protease inhibitors in patients with HIV: the role of hepatitis B and C virus infection. J Acquir Immune Defic Syndr
59. den Brinker M, Wit FW, Wertheim-van Dillen PM, et al. Hepatitis B and C virus co-infection and the risk for hepatotoxicity of highly active antiretroviral therapy in HIV-1 infection. AIDS
60. Sulkowski M, Thomas DL, Mehta SH, et al. Hepatoxicity associated with nevirapine or efavirenz-containing antiretroviral therapy: Role of hepatitis C and B infections. Hepatology
61. Sulkowski M, Thomas DL, Chaisson RE, et al. Hepatoxicity associated with antiretroviral therapy in adults infected with human immunodeficiency virus and the role of hepatitis C or B virus infection. JAMA
62. Becker S. Liver toxicity in epidemiological cohorts. Clin Infect Dis
63. Sulkowski MS, Mehta SH, Chaisson RE, et al. Hepatotoxicity associated with protease inhibitor-based antiretroviral regimens with or without concurrent ritonavir. AIDS
64. Centers for Disease Control and Prevention. Guidelines for preventing opportunistic infections among HIV-infected persons-2002 Recommendations of the U.S. Public Health Service and the Infectious Diseases Society of America. MMWR
65. Centers for Disease Control and Prevention. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States. MMWR
66. Centers for Disease Control and Prevention. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States Recommendations of the Advisory Committee on Immunization Practices (ACIP) Part II: immunization of adults. MMWR
67. Collier AC, Corey L, Murphy VL, et al. Antibody to human immunodeficiency virus (HIV) and suboptimal response to hepatitis B vaccination. Ann Intern Med
68. Overton ET, Sungkanuparph S, Powderly WG, et al. Undetectable HIV plasma RNA load predicts success after hepatitis B vaccination in HIV-infected persons. Clin Infect Dis
69. Quaglio G, Talamini G, Lugoboni F, et al. Compliance with hepatitis B vaccination in 1175 heroin users and risk factors associated with lack of vaccine response. Addiction
70. Rey D, Krantz V, Partisani M, et al. Increasing the number of hepatitis B vaccine injections augments anti-HBs response rate in HIV-infected patients. Effects on HIV-1 viral load. Vaccine
71. Wong EK, Bodsworth NJ, Slade MA, et al. Response to hepatitis B vaccination in a primary care setting: influence of HIV infection, CD4+ lymphocyte count and vaccination schedule. Int J STD AIDS
72. Keet IP, van Doornum G, Safary A, et al. Insufficient response to hepatitis B vaccination in HIV-positive homosexual men. AIDS
73. Tayal SC, Sankar KN. Impaired response to recombinant hepatitis B vaccine in asymptomatic HIV-infected individuals. AIDS
74. Kim HN, Harrington RD, Van Rompaey SE, et al. Predictors of lack of response to hepatitis B vaccination in HIV-infected patients. 44th Annual Meeting of the Infectious Diseases Society of America, 12-15 October, Toronto, Ontario, Canada. Abstract 1199. 2006.
75. Wang C, Tang J, Song W, et al. HLA and cytokine gene polymorphisms are independently associated with responses to hepatitis B vaccination. Hepatology
76. Mannucci PM, Zanetti AR, Gringeri A, et al. Long-term immunogenicity of a plasma-derived hepatitis B vaccine in HIV seropositive and HIV seronegative hemophiliacs. Arch Intern Med
77. Verthelyi D, Wang VW, Lifson JD, et al. CpG oligodeoxynucleotides improve the response to hepatitis B immunization in healthy and SIV-infected rhesus macaques. AIDS
78. Krieg AM. CpG motifs in bacterial DNA and their immune effects. Annu Rev Immunol
79. Hadler SC, Francis DP, Maynard JE, et al. Long-term immunogenicity and efficacy of hepatitis B vaccine in homosexual men. N Engl J Med
80. Hadler SC, Judson FN, O'Malley PM, et al. Outcome of hepatitis B virus infection in homosexual men and its relation to prior human immunodeficiency virus infection. J Infect Dis
81. Hadler SC, Coleman JC, O'Malley PM, et al. Evaluation of long-term protection by hepatitis B vaccine for seven to nine years in homosexual men in viral hepatitis and liver disease. In: Hollinger FB, Lemon SM, Margolis H, eds. Proceedings of the 1990 International Symposium on Viral Hepatitis and Liver Disease-Contemporary Issues and Future Prospects
. Baltimore: Williams and Wilkins; 1991.
82. Landrum ML, Hullsiek KH, Ganesan A, et al. The clinical efficacy of hepatitis B vaccine in HIV-1 infected individuals. Final Program and Abstracts of the 45th Annual Meeting of the Infectious Diseases Society of America
. San Diego, CA. Arlington, VA: Infectious Diseases Society of America; 2007.
83. Heffernan RT, Barrett NL, Gallagher KM,. Declining incidence of invasive Streptococcus pneumoniae infections among persons with AIDS in an era of highly active antiretroviral therapy, 1995-2000. J Infect Dis
84. Jordano Q, Falco V, Almirante B,. Invasive Pneumococcal Disease in Patients Infected with HIV: Still a Threat in the Era of Highly Active Antiretroviral Therapy. Clin Infect Dis
85. Tacconelli E, Tumbarello M, de Gaetano K,. Highly active antiretroviral therapy decreases the incidence of bacteremia in human immunodeficiency virus-infected individuals. Clin Infect Dis
86. Barry PM, Zetola N, Keruly JC,. Invasive pneumococcal disease in a cohort of HIV-infected adults: incidence and risk factors, 1990-2003. AIDS
87. Nuorti JP, Butler JC, Gelling L,. Epidemiologic relation between HIV and invasive pneumococcal disease in San Francisco County, California. Ann Intern Med
88. Redd SC, Rutherford GW 3rd, Sande MA,. The role of human immunodeficiency virus infection in pneumococcal bacteremia in San Francisco residents. J Infect Dis
89. Hibbs JR, Douglas JM, Judson FN,. Prevalence of human immunodeficiency virus infection, mortality rate, and serogroup distribution among patients with Pneumococcal bacteremia at Denver General Hospital, 1984-1994. Clin Infect Dis
90. Fry AM, Facklam RR, Whitney CG,. Multistate evaluation of invasive pneumococcal diseases in adults with human immunodeficiency virus infection: serotype and antimicrobial resistance patterns in the United States. J Infect Dis
91. Grau I, Pallares R, Tubau F,. Epidemiologic changes in bacteremic pneumococcal disease in patients with human immunodeficiency virus in the era of highly active antiretroviral therapy. Arch Intern Med
92. Centers for Disease Control and Prevention. Prevention of pneumococcal disease: recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep
93. Falco V, Jordano Q, Cruz MJ,. Serological response to pneumococcal vaccination in HAART-treated HIV-infected patients: one year follow-up study. Vaccine
94. Glaser JB, Volpe S, Aguirre A,. Zidovudine improves response to pneumococcal vaccine among persons with AIDS and AIDS-related complex. J Infect Dis
95. Janoff EN, Fasching C, Ojoo JC,. Responsiveness of human immunodeficiency virus type 1-infected Kenyan women with or without prior pneumococcal disease to pneumococcal vaccine. J Infect Dis
96. Nielsen H, Kvinesdal B, Benfield TL,. Rapid loss of specific antibodies after pneumococcal vaccination in patients with human immunodeficiency virus-1 infection. Scand Infect Dis
97. Rodriguez-Barradas MC, Alexandraki I, Nazir T,. Response of human immunodeficiency virus-infected patients receiving highly active antiretroviral therapy to vaccination with 23-valent pneumococcal polysaccharide vaccine. Clin Infect Dis
98. Rodriguez-Barradas MC, Musher DM, Lahart C,. Antibody to capsular polysaccharides of Streptococcus pneumoniae after vaccination of human immunodeficiency virus-infected subjects with 23-valent pneumococcal vaccine. J Infect Dis
99. Kroon FP, van Dissel JT, Ravensbergen E,. Antibodies against pneumococcal polysaccharides after vaccination in HIV-infected individuals: 5-year follow-up of antibody concentrations. Vaccine
100. Janoff EN, Douglas JM, Gabriel M,. Class-specific antibody response to pneumococcal capsular polysaccharides in men infected with Human Immunodeficiency Virus Type 1. J Infect Dis
101. Huang KL, Ruben FL, Rinaldo CR,. Antibody responses after influenza and pneumococcal immunization in HIV-infected homosexual men. JAMA
102. Rodriguez-Barradas MC, Groover JE, Lacke CE,. IgG antibody to pneumococcal capsular polysaccharide in Human Immunodeficiency Virus-infected subjects: persistence of antibody in responders, revaccination in nonresponders, and relationship of immunoglobulin allotype to response. J Infect Dis
103. Breiman RF, Keller DW, Phelan MA,. Evaluation of effectiveness of the 23-valent pneumococcal capsular polysaccharide vaccine for HIV-infected patients. Arch Intern Med
104. Gebo KA, Moore RD, Keruly JC,. Risk factors for pneumococcal disease in human immunodeficiency virus-infected patients. J Infect Dis
105. French N, Nakiyingi J, Carpenter LM,. 23-Valent pneumococcal polysaccharide vaccine in HIV-1-infected Ugandan adults: double-blind, randomised and placebo controlled trial. Lancet
106. Lopez-Palomo C, Martin-Zamorano M, Benitez E,. Pneumonia in HIV-infected patients in the HAART era: incidence, risk, and impact of the pneumococcal vaccination. J Med Virol
107. French N, Moore M, Haikala R,. A case-control study to investigate serological correlates of clinical failure of 23-valent pneumococcal polysaccharide vaccine in HIV-1-infected Ugandan adults. J Infect Dis
108. Musher DM, Phan HM, Watson DA,. Antibody to capsular polysaccharide of Streptococcus pneumoniae at the time of hospital admission for pneumococcal pneumonia. J Infect Dis
109. Subramaniam KS, Segal R, Lyles RH,. Qualitative change in antibody responses of Human Immunodeficiency Virus-infected individuals to pneumococcal capsular polysaccharide vaccination associated with highly active antiretroviral therapy. J Infect Dis
110. Radwan HM, Cheeseman SH, Lai KK,. Influenza in human immunodeficiency virus-infected patients during the 1997-1998 influenza season. Clin Infect Dis
111. Fine AD, Bridges CB, De Guzman AM,. Influenza A among patients with human immunodeficiency virus: an outbreak of infection at a residential facility in New York City. Clin Infect Dis
112. Centers for Disease Control and Prevention. Prevention and control of influenza: recommendations of the advisory committee on immunization practices (ACIP). MMWR
. 2006;55(RR 10):1-42.
113. Atashili J, Kalilani L, Adimora AA. Efficacy and clinical effectiveness of influenza vaccines in HIV-infected individuals: a meta-analysis. BMC Infect Dis
114. Yamanaka H, Teruya K, Tanaka M,. Efficacy and immunologic responses to influenza vaccine in HIV-1-infected patients. J Acquir Immune Defic Syndr
115. Tasker SA, Treanor JJ, Paxton WB,. Efficacy of influenza vaccination in HIV-infected persons. A randomized, double-blind, placebo-controlled trial. Ann Intern Med
116. Kroon FP, van Dissel JT, Labadie J,. Antibody response to diphtheria, tetanus, and poliomyelitis vaccines in relation to the number of CD4+ T lymphocytes in adults infected with human immunodeficiency virus. Clin Infect Dis
117. Overton ET, Nurutdinova D, Sungkanuparph S,. Predictors of immunity after hepatitis A vaccination in HIV-infected persons. J Viral Hepat
118. Rimland D, Guest JL. Response to hepatitis A vaccine in HIV patients in the HAART era. AIDS
119. Weissman S, Feucht C, Moore BA. Response to hepatitis A vaccine in HIV-positive patients. J Viral Hepat
120. Wallace MR, Brandt CJ, Earhart KC,. Safety and immunogenicity of an inactivated hepatitis A vaccine among HIV-infected subjects. Clin Infect Dis
121. Garland SM, Hernandez-Avila M, Wheeler CM,. Quadrivalent vaccine against human papillomavirus to prevent anogenital diseases. N Engl J Med
122. The FUTURE II Study Group. Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. N Engl J Med
123. Markowitz LE, Dunne EF, Saraiya M,. Quadrivalent human papillomavirus vaccine: recommendations of the advisory committee on immunization practices (ACIP). MMWR
124. Palefsky JM. Human papillomavirus infection and anogenital neoplasia in human immunodeficiency virus-positive mena and women. J Natl Cancer Inst Monogr
125. Palefsky JM, Holly EA, Ralston ML,. Prevalence and risk factors for anal human papillomavirus infection in human immunodeficiency virus (HIV)-positive and high-risk HIV-negative women. J Infect Dis
126. Palefsky JM, Holly EA, Ralston ML,. Prevalence and risk factors for human papillomavirus infection of the anal canal in human immunodeficiency virus (HIV)-positive and HIV-negative homosexual men. J Infect Dis
127. Palefsky JM, Minkoff H, Kalish LA,. Cervicovaginal human papillomavirus infection in human immunodeficiency virus-1 (HIV)-positive and high-risk HIV-negative women. J Natl Cancer Inst
128. Piketty C, Darragh TM, Da Costa M,. High prevalence of anal human papillomavirus infection and anal cancer precursers among HIV-infected persons in the absence of anal intercourse. Ann Intern Med
129. Block SL, Nolan T, Sattler C,. Comparison of the immunogenicity and reactogenicity of a prophylactic quadrivalent human papillomavirus (Types 6, 11, 16, 18) L1 virus-like particle vaccine in male and female adolescents and young adult women. Pediatrics
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