Advanced search
Publication Cover
Human Vaccines & Immunotherapeutics Volume 20, 2024 - Issue 1
Submit an article Journal homepage
862
Views
0
CrossRef citations to date
0
Altmetric
Zoster

Immunogenicity and safety of live attenuated and recombinant/inactivated varicella zoster vaccines in people living with HIV: A systematic review

Valentina Cartaa Istituto Zooprofilattico Sperimentale della Lombardia e dell’Emilia-Romagna, Brescia, ItalyView further author information
,
Lucia Mangeria Istituto Zooprofilattico Sperimentale della Lombardia e dell’Emilia-Romagna, Brescia, ItalyView further author information
,
Giorgio Tieccob Department of Clinical and Experimental Sciences, University of Brescia-ASST Spedali Civili, Brescia, ItalyView further author information
,
Emanuele Focàb Department of Clinical and Experimental Sciences, University of Brescia-ASST Spedali Civili, Brescia, ItalyView further author information
,
Eugenia Quiros-Roldanb Department of Clinical and Experimental Sciences, University of Brescia-ASST Spedali Civili, Brescia, ItalyView further author information
&
Maria Antonia De Francescoc Department of Molecular and Translational Medicine, Institute of Microbiology, University of Brescia-ASST Spedali Civili, Brescia, ItalyCorrespondence[email protected]
ORCID Iconhttps://orcid.org/0000-0003-2221-6286View further author information
ORCID Icon
Article: 2341456 | Received 16 Jan 2024, Accepted 07 Apr 2024, Published online: 22 Apr 2024

ABSTRACT

Few papers focus their attention on VZV vaccination effectiveness among people living with HIV (PLWH). Flanking the live attenuated vaccine (VZL) available, a newly recombinant vaccine (RZV) was recently introduced and approved for HZ prevention among adults. PLWH represents a population on which a particular attention should be applied, in order to guarantee the vaccine efficacy and safety. We performed a literature search in USNLM, PubMed, PubMed Central, PMC and Cochrane Library. From all the publications found eligible, data were extracted and processed per population, vaccine type, immunogenicity and ADRs. The review of the 13 included studies shows that both RZV and VZL are immunogenic and have an acceptable safety profile in adults and children living with HIV. However, given the lack of research available about vaccine efficacy in preventing VZV and HZ in PLWH, additional studies need to be performed, in order to achieve a full completeness of data.

Introduction

Varicella-zoster virus (VZV) is a human neurotropic DNA virus belonging to the alpha Herpesviridae family. The primary VZV infection is a highly contagious and self-limiting disease though responsible for severe complications in pregnant women, neonates and immunocompromised subjects.Citation1 The virus persists then in a long-life latent state in the cranial nerve and dorsal root ganglia.Citation2 Natural infection produces both humoral and cell mediated immunity. VZV-specific T cell immunity is anyway important to hold the virus in the latent phase.Citation3 Since 2006, a universal immunization program to VZV has been recommended for all children, with two doses of live attenuated VZV vaccine given at age 12–15 months and age 4–6 years.Citation4–6

To prevent severe varicella disease course and complications, such as hepatitis, pneumonia and encephalitis,Citation7–9 VZV vaccination has also been advised for children living with HIV (CLWH) with two doses, at least 3 months apart.Citation4 Because of the safety problems associated with the use of a live vaccine, the vaccination has initially recommended for children with stable HIV disease and CD4 T lymphocytes ≥25%,Citation10,Citation11 extended successively to children with CD4 T lymphocytes ≥15%Citation4,Citation12About 79% of vaccinated CLWH with CD4 T lymphocytes ≥15% developed both humoral and cellular immunity, even if it was showed that detectable viremia at baseline correlated with lower likelihood of immunization response.Citation12

Furthermore, protective antibody levels following vaccination may wane in CLWH,Citation13,Citation14 leading to a potential reservoir of susceptible children because life expectancy is increased with the introduction of antiretroviral therapy (ART).

VZV memory CD4 cells decline with the age becoming undetectable in 30–40% of the subjects after the age of 55 yearsCitation15 and in patients with immunosuppression leading to the herpes zoster (HZ) manifestation as a reactivation of VZV.Citation16–19 HZ is characterized by a unilateral vesicular rash associated with radicular pain on one side of the body.Citation20 The most frequent complication is postherpetic neuralgia followed by ocular and visceral disorders.Citation2

HZ constitutes an important public health challenge responsible for morbidity and, to a lesser extent, for mortality in non-vaccinated subjects aged ≥50 years.Citation21 In Europe, more than 1.7 million cases are estimated each year.Citation22

Compared with the general population, the immunocompromised subjects are at higher risk to develop more severe and life-threatening HZ complications, often requiring hospitalization.Citation23–26

Even if with the implementation of antiretroviral therapy (ART), HZ has decreased in people living with HIV (PLWH),Citation27 different studies show that this population has still a higher incidence of HZ than the general population.Citation28–30

This may be related to different problems, such as suboptimal adherence to antiretroviral therapy, partial immune reconstitution, persistent stress and accelerated/premature aging.Citation31,Citation32

The population living with HIV is getting older; it was, in fact, estimated that in 2030 about 73% of ART experienced patients will be aged 50 years or older, leading to an increase of age-related diseases, of multi-drug regimens and to a higher number of patients with potential complications associated with HIV therapy.Citation33

Then, in recent years, premature aging, that is linked to non-chronological biological aging due to an increased cellular senescence, has turned increasingly important in HIV infection.Citation34

In fact, it was found that PLWH over 30 years old already exhibit a higher risk for HZ compared to uninfected and more elderly subjects. Furthermore, this risk was mostly noticeable in subjects with a nadir CD4 count below 200 cells/ml.Citation35 Antiviral therapy is included as prophylaxis in individuals at higher risk for HZ. This therapy is often ineffective because of potential drug toxicities, prolonged treatment durations, viral resistance, and drug-drug interactions especially in such patients subjected to the use of multiple drugs.Citation36

Therefore, vaccination may be considered an effective prophylactic measure and to analyze the vaccines immunogenicity, their safety and efficacy become a fundamental issue in high-risk PLWH groups with low CD4 counts. To date, two vaccines are available. The zoster vaccine live (ZVL) licensed in 2006 and given in a single dose, which contains an increased viral titer (14-fold) than the same live attenuated VZV used as varicella vaccine (Zostavax; MSD) and the recombinant VZV vaccine (RZV) approved in 2017 and given in two doses (Shingrix; GSK). It consists of a combination of the VZV glycoprotein E antigen and a liposome formulation AS01B adjuvant system.Citation37 A systematic review shows that both ZVL and RZV are effective in preventing HZ reactivation for up to 3 years.Citation38 This review includes 26 studies comprising 90,259 healthy older adults with a mean age of 63.7 years and with no immunosuppression. Four studies have the objective to evaluate the cumulative incidence of herpes zoster in groups that received ZVL vaccine versus placebo including 6980 subjects. The cumulative incidence of herpes zoster at up to three years of follow‐up was lower in participants who received the ZVL (one dose) than in those who received placebo (risk ratio (RR) 0.49, 95% confidence interval (CI) 0.43 to 0.56; risk difference (RD) 2%; number needed to treat for an additional beneficial outcome (NNTB) 50; moderate‐certainty evidence).Citation38 Similarly, two studies, including 22,022 subjects, found that the cumulative incidence of herpes zoster at 3.2 years of follow-up was lower in subjects vaccinated with RZV (two doses) than subjects vaccinated with placebo (RR 0.08, 95% CI 0.03 to 0.23; RD 3%; NNTB 33; moderate‐certainty evidence).Citation38

In Europe, ZVL is approved for the prevention of HZ in adults aged ≥50 years and not recommended in severely immunocompromised individuals for the possibility to give rise to fatal disseminated disease due to the vaccine strain.Citation39 The RZV vaccine is advised for the prevention of HZ in adults aged ≥50 years and adults aged ≥18 years, including immunodeficient or immunosuppressed individuals.Citation40,Citation41

We first planned to review the clinical efficacy of VZ and HZ vaccines in CLWH and adults living with HIV (ALWH), but in literature we could not find efficacy data available for them. Studies on clinical efficacy require great number of participants, an issue that will likely never be reached in specific populations at higher risk, such as CLWH and ALWH. Therefore, another way to proceed is to look for immunogenicity, as a surrogate marker for clinical efficacy and a correlate of disease protection. Several studies have addressed the immunogenicity of ZVL and RZV in both CLWH and ALWH. These populations need particular attention because humoral and cellular immunity might be suboptimal and vaccine efficacy might vary according to the type of vaccine, the immunodeficiency grade and the use of concomitant drugs.

Therefore, the scope of this systematic review was to summarize the data regarding the immunogenicity of these vaccines in CLWH and ALWH and to provide an answer to the following questions:

  1. Do live attenuated vaccines induce immunogenicity in CLWH?

  2. Do live attenuated vaccines induce immunogenicity in ALWH?

  3. Do recombinant/inactivated vaccines induce immunogenicity in ALWH?

  4. What is the safety profile of vaccination strategies for active immunization against varicella in CLWH?

  5. What is the safety profile of vaccination strategies for active immunization against herpes zoster in ALWH 50 years and older?

Some of the included studies, however, did not report relevant information about ART coverage, viral load and CD4 count. The viro-immunological status and use of ART at the time of immunization is of crucial importance in maintaining seroprotection and the absence of these data might contribute to a potential source of bias or confounding factors.

However, the results may give useful information to clinicians about the use of these vaccines in people living with HIV (PLWH) and about the possible complications associated with them.

Methods

Protocol

The reporting of this systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) updated guideline for systematic review stated in 2020.Citation42 The final version of the protocol was registered in PROSPERO (CRD42023485837).

Eligibility criteria

PICOS (population, intervention, comparator, outcome and study) was used to determine eligibility criteria. The study population consisted of CLWH aged nine months to 12 years and ALWH ≥50 years. All subjects received vaccine (varicella vaccine or ZVL or RVZ). Comparators were subjects receiving placebo or unvaccinated subjects. The primary outcome was the immunogenicity of live and inactivated/recombinant vaccines. Secondary outcome was vaccine safety including localized and systemic adverse reactions.

We included randomized and non-randomized clinical trials, case reports, prospective and retrospective clinical studies. Studies reporting only data on immunocompetent children or adults were excluded. Articles published in non-English language, pre-print or ahead of print analysis, pre-clinical studies, animal studies, letters to the editor, conference articles, commentaries, viewpoints, reviews, systematic reviews, and meta analysis were also excluded.

Information sources and search strategy

Two researchers (VC and LM) independently screened the literature by title and abstracts, selected the articles according to the established criteria and checked each other results. The literature search was performed in the United States National Library of Medicine, PubMed (last accessed November 2023), PubMed Central, PMC (last accessed November 2023) and Cochrane Library (last accessed November 2023). Search terms for the different databases were “HIV” AND “Vaccine” AND “VZV” AND “HZ.” Three other researchers (MADF, EQR and EF) revised the included and the rejected papers. Then, three researchers (VC, LM, and GT) considered each selected article full text to collect data that were revised, compared and synthesized using a detailed database. Disagreement was resolved by a joint discussion that included all authors.

Data items

Once eligible publications were identified, the relevant data were extracted in an Excel database.

Data from each of the selected studies were independently extracted by two reviewers (VC and LM). Discrepancies in any extracted data points were resolved by discussion between authors (VC and LM) and in case of non-consensus by consulting with a third additional review author (GT).

Extracted data included publication details (author, journal, and year), geographical area, study type/design, population (age group and gender), sample size, intervention measures (type of vaccine, dosages and immunization schedules), method of immune response evaluation, primary and secondary outcomes, number of CD4+ T cells, antiretroviral therapy and HIV viral load. Missing or unclear data were reported as “non-available” (NA).

Synthesis methods

All the collected data were reported in a single table where every column was specifically associated with a different item. We limited our study to a descriptive analysis of our search findings due to the wide heterogenicity of the selected articles. Immunogenicity outcomes are presented as per original publication, including humoral and cellular immune responses. The percentage calculation was performed in consideration of the number of data available for each specific item. This is not a meta-analysis and, according to the most updated PRISMA guidelines, no models to identify the presence and extent of statistical heterogeneity or sensitivity analysis to assess the robustness of the synthesized results were performed.

Bias and certainty assessment

Since the clinical, methodological and statistical heterogenicity of the selected articles, we limited our systematic review to a descriptive analysis. Risk of bias or certainty (or confidence) in the body of evidence was not assessed.

Results

Study selection and search results

A total of 1029 papers were identified through our search. We excluded 13 non-English articles, and a further 986 analyzes as their abstract did not meet the inclusion criteria. The remaining 30 articles were assessed for eligibility by a full-text analysis. Thirteen studies did not meet or the population (no mention of PLWH) or the design criteria (studies were not focused on vaccination). Furthermore, four reviews were excluded. Eventually, 13 studies were included as shown in the following flow diagram ().

Figure 1. Adapted PRISMA 2020 Flow Diagram.

Figure 1. Adapted PRISMA 2020 Flow Diagram.

Studies included were randomized clinical trials (3/13, 23%), not randomized clinical trials (4/13, 31%), case reports (2/13, 15.3%), retrospective studies (1/13, 7.6%) and prospective studies (2/13, 15.3%). These analyses were carried out prevalently in the USA (9/13, 69.2%), and equally among adults (6/13, 46.1%) and children (6/13, 46.1%). One study included both adults and children (1/13, 7.6%). The study design, number of patients, demographic data, vaccines used, and endpoints are summarized in .

Table 1. Characteristics of included studies.

Results of synthesis

A total of 482 adults living with HIV, mostly male (344/482, 71.4%), were included. Most data aimed to compare 1 or 2 doses (6/13 studies, 23% in 348/482 adults, 72.2%) of live attenuated varicella zoster vaccine (Varivax and Zostavax, Oka Merck) to a saline placebo or lyophilized sucrose reconstituted with saline. Then, considering the available demographic data, the gE-AS01B adjuvanted subunit vaccine (RZV HZ/su, GSK) (3 doses in 74/482 adults, 15.4%), and the heat-treated VZV vaccine (ZVHT; 1–4 doses in 60/482 adults, 12.4%) were the other used vaccines. Overall, adults living with HIV were on ART (421/431, 97.7%) with undetectable viremia (361/371, 97.3%), but half of them with a CD4+ cells count below 200 cells/mm3 (213/421, 50.6%) ().

Table 2. Demographic and clinical characteristics of all populations, type of vaccines and geographical areas of the included studies.

As regards CLWH, 509 subjects were included, receiving all live attenuated varicella zoster vaccines. Vaccine types used were Oka/Merck (97/509 children, 19.1%) (2 doses) and Okavax Sanofi (60/509 children, 11.8%) (2 doses). Use of ART was available only in a few studies. Available data show that children were prevalently on-ART (70/75, 93.3%) with a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen (36/59, 61.0%) ().

Immunogenicity of varicella vaccine in ALWH

Humoral and cell mediated immunity were measured by different methods in the various included studies. In two studies,Citation43,Citation44 VZV IFN-γ ELISPOT assay was performed to directly measure the presence of IFN-γ-secreting VZV-specific peripheral blood mononuclear cells (PBMCs), while VZV immunoglobulin G (IgG) antibodies to glycoprotein E were measured before and after vaccination by ELISA.

In the study of Mullane et al.,Citation43 the HIV population consisted of patients with CD4+ cell count ≤200 cells/mm3 documented within 90 days prior to dose 1 and to be receiving ART for at least 30 days prior to enrollment.

They found that ZVHT recipients had significantly higher antibody levels than placebo recipients after four doses () with titers that increased significantly compared to the baseline (geometric mean fold rise, GMFR = 2.4 [90% CI, 1.8–3.0], p < .0001). The geometric mean concentrations of IFN-γ were higher in ZVHT than among placebo group (). However, the cell immune response was significantly higher than that at baseline (GMFR = 3.0 [90% CI, 2.0–4.6], p < .0001).

Table 3. Humoral and cell mediated immune response rate in adults detected in each study.

Benson et al.Citation44 included in the study ALWH with CD4+ T-cell counts ≥200 cells/mm3 on a stable ART regimen (no change within 90 days prior to entry) and undetectable plasma HIV RNA levels (lower limit of detection <75 copies/mL) within 90–180 days of entry.

They found that patients receiving ZV had significantly higher antibody levels (p < .001) than placebo () with titers that increased significantly compared to the baseline (geometric mean fold rise, GMFR = 1.80 [90% CI, 1.66–1.95], p < .001). Furthermore, they found that the group with higher CD4+ T cell counts (≥350 cells/mm3) had significantly higher antibody titers (p = .003) than the group with lower CD4+ T cell counts (≥200–349 cells/mm3) (data not shown in the study). The geometric mean concentrations of IFN-γ were higher in the Zostavax group than placebo group () and the cell immune response was higher, even if not significantly, than that at baseline (GMFR = 3.8 [90% CI, 1.8–8.0], p value = 0.17).

The study of Berkowitz et al.Citation45 included three cohorts of ALWH: ART recipients with a high CD4+ T-cell count (≥200 cells/mm3, ART recipients with a low CD4+ T-cell count (50–199 cells/mm3), and ART-naive adults with a high CD4+ T-cell count (≥500 cells/mm3).

Cell-mediated immune responses were defined as a ≥2-fold increase over the pre-vaccination baseline in the frequency of viable CD4+ T cells expressing two or more activation markers (CD4 2+ T-cells) per 106 CD4 T cells. Anti-gE humoral response to the vaccine was defined as a post vaccination ≥4-fold increase compared to the pre-vaccination baseline or to the assay cutoff.

In this study, the majority of subjects (94/123) were on ART treatment with a high CD4+ count (≥200 cells/mm3). In the overall study population, the median frequency of gE-specific CD42+ T-cells increased in the RZV group but not in the saline group (p < .0001). The anti-gE GMCs increased significantly after three RZV doses and were maximal 1 month after the last dose. In the RV group, the proportion of subjects with anti-gE humoral vaccine responses was 96.2% and the proportion of subjects with cellular immune responses was 90% at 7 months after 3 doses, whereas they were ≤2.8% in the saline group (). The humoral and cellular immune responses were higher in the recombinant HZ recipients compared to placebo recipients at month 7 in subjects in the combined ART/high CD4+, ART/low CD4+ and ART naïve/high CD4+ cohorts, even if the number of the last one groups are very low ().

Table 4. Immunogenicity recombinant zoster vaccine according to the number of CD4 cells and to the antiretroviral therapy (ART).

ALWH enrolled in the study of Weinberg et al.Citation46 had CD4+T cells ≥400 cells/mm3 and were on stable treatment. Only cellular immunity was assessed in this study. Methods used were vaccine responder cell frequency (RCF) and ELISPOT assay. In HIV-infected subjects, at 12 weeks after the second dose of live attenuated vaccine, there was a significant increase in RCF values (p = .02) compared to baseline and a trend toward an increase in ELISPOT results, even if not statistically significant (p = .08).

Immunogenicity of varicella vaccine in CLWH

The study by Levin et al.Citation12 included a group in clinical category A, B, or N and immunologic category 2 (group I in our review) and a group (group II in our review) in CDC clinical category C and/or immunologic category 3 (). Anti-VZV antibodies were detected using the fluorescent antibody membrane assay (FAMA). Cell immunity responses were evaluated by a lymphocyte proliferation assay (LPA) in response to VZV antigens and by RCF. The results were expressed as percentage of positive subjects over the total vaccinated group. After 8 weeks following the second dose of live attenuated vaccine, 64.8% and 70.6% of the children belonging to the different CDC category produced an antibody response. Two-thirds of vaccine recipients in groups I and II had VZV-specific CMI detectable by RCF and LPA assays after 2 doses of vaccine ().

Table 5. Humoral and cell-mediated immune in children according to the different studies.

In the study of Taweesith,Citation47 it was assessed only humoral immunity by ELISA assay. Out of 34 children, 18 were in CDC category A, B, or N and 9 were in CDC category C. Both produced antibody responses (81.8% and 75%, respectively), even if they found that the subjects who had VZV protective antibody were less likely to have CDC clinical category C and had higher CD4+ percentage at time of varicella vaccination and longer duration of ART (p < .05).

The cohort population in the study of Bekker et al.Citation48 consisted of 15 HIV seropositive patients, 7 belonging to CDC category A, B, or N and 8 to CDC category C. At 6 weeks after the second immunization, 9/15 children (60%) seroconverted, while in the HIV negative siblings the response rate was 100% (6/6). Furthermore, the anti-VZV IgG titers in CLHW after two vaccine doses against VZV were significantly lower than those of the HIV-negative siblings (median 0.2 versus 4.6 IU/ml, p = .002) (). The cellular immune response was determined after stimulation with VZV antigen using a 5,6-carboxyfluorescein diacetate succinimidyl ester (CFSE) dye dilution assay and expressed as stimulation index (SI). The median CD4 SI at 6 weeks after the second vaccination was 4.2 in CLWH and 3.9 in HIV-negative children. The median CD8 SI reached 1.5 in CLWH and 1.6 in HIV-negative children ().

In the study of Armenian et al.,Citation49 cellular immunity was evaluated by LPA and humoral immunity by an ELISA. All the ten children included in the study belonged to the CDC category N. All the children produced a positive VZV-LPA response, while VZV IgG antibodies were detected in 6/9 (66.6%) children ().

The study cohort, included in the study of Gershon et al.,Citation50 consisted of 46 children with a mean age of 9.3 years; a mean CD4+ count of 803 cells/mm3 and a mean CD4% of 33%. Their median viral load was 2.7 Log10 copies/mm.Citation3 Antibodies to VZV were measured by FAMA, while VZV-specific CMI was measured by a modified ELISPOT assay and an RCF assay. The proportion of seropositive subjects reached 95% after 12 weeks following the second dose. The ELISPOT assay, which measured anti-VZV effector CD4+ T cell responses, was positive in 65% of the patients after the second dose of the vaccine. The responder cell frequency assay, which measured anti-VZV memory CD4+ T cell responses, was positive in 33.4% of the subjects at 12 weeks after the second dose ().

In the study of Purswani et al.,Citation51 humoral immunity tested by ELISA showed that over 269 HIV perinatally infected children, 145 (53.9%) seroconverted after 3 weeks following the second dose ().

Safety in ALWH

Adverse drug reactions (ADRs) were reported in 464 ALWH, and a total of 890 ADRs were considered as the same person might have experienced more than a single undesirable effect.Citation52–54 Regardless of the vaccine type or scheme used, ADRs were mainly systemic (510/890, 57.3%), especially fatigue (107/519, 21%), headache (92/107, 18%), and gastrointestinal symptoms (45/510, 8.8%). Fever (36/510, 7.1%), or rash (20/519, 3.9%) were less frequently reported. In case of more than one dose of vaccine administration, ADRs happened similarly after the first dose (245/702, 34.9%), and after the subsequent ones (2nd dose: 251/702, 35.8%; 3rd dose: 206/702, 29.3%). Three severe ADRs were reported after a single dose of ZVL (retinal necrosis, and aseptic meningitis) and after two doses of ZVL (disseminated vaccine-strain VZV infection, respiratory failure and sepsis), while all the other ADRs were considerable as mild-to-moderate (888/890, 99.8%). Considering recombinant RZV, a gradual decline in injection site reactions has been recorded (1st dose: 98/242, 40.5%; 2nd dose 87/242, 36.0%; 3rd dose 57/242, 23.6%) ().

Table 6. Adverse reactions in Adults.

Safety in CLWH

In regards to CLWH, a total of 103 ADRs were reported in 224 patients.Citation54 Regardless of vaccine scheme of administration, systemic reactions occurred more frequently than local site ones (69/103, 67.0% vs 34/103, 33.0%). Considering the available data, ADRs in children were mostly categorized as CDC class N (not symptomatic), A (mildly symptomatic) or B (moderately symptomatic) (51/61, 83.6%), rather than C (severely symptomatic) (10/61, 16.4%). In case of live attenuated VZV vaccine administration, fever (20/103, 19.4%), and rash (9/103, 8.7%) were prevalently recorded. Four cases of neutropenia were reported, of whom one case of grade 4 severity ().

Table 7. Adverse reaction in children*.

Discussion

In this systematic review, we analyzed the immunogenicity of both live attenuated and recombinant/inactivated VZV vaccines in PLWH including both children and adults. Scientific literature regarding recombinant ZV in immunocompromised patients is scarce because of its recent approval.Citation55–62 Most of the analyzed studies (11/13, 84.6%) in fact used the live attenuated VZV vaccine, only one the recombinant ZV vaccine (1/13, 7.6%) and the other one (1/13, 7.6%) a heat inactivated ZV vaccine.

In adults, both live and heat inactivated/recombinant VZV vaccines elicited strong humoral immunity, mostly after two doses, with significantly increased mean titers of anti-gE antibody concentration compared to placebo recipients.Citation43–45 The frequency of glycoprotein E-specific CD42+ T-cells was higher in recombinant ZV recipients compared to placebo recipients,Citation45 while the magnitude of cellular immunity was not significantly increased in live attenuated vaccine VZV recipients after 2/3 doses with respect to placebo group across the different studies, even if it was higher compared to the values of baseline.

This difference might have an important impact in preventing HZ in PLWH. In healthy subjects, t was already shown that the recombinant ZV vaccine confers greater protection against VZV reactivation than live attenuated vaccines, which is ascribed to glycoprotein E adjuvanted with AS01B, which can enhance VZV-specific T-cell memory responses.Citation63,Citation64 A study analyzing T cell memory responses to the two types of vaccines found higher responses persisting for five years in recombinant ZV recipients.Citation65

Most studies did not stratify the results according to the age or the immunocompromising status. Patients had mostly CD4+T cell counts >200 cell/mm3 and were on ART. Berkowitz et al.Citation36 analyzed different groups of patients according to different number of CD4+T cells and presence of ART. However, the study included only a few patients with very low CD4+ T cell counts, even if it has been found no impact on HIV RNA concentrations or CD4+ T cell numbers during the study. In children, about two-thirds of the subjects who received at least two doses of live attenuated VZV vaccine seroconverted and developed cellular immunity across the studies where it was assessed (4/6 studies, 67%).

Humoral and cellular immunity were evaluated at variable times after the second dose of vaccine mostly ranging from 3 weeks to 24 weeks. The longitudinal analysis of humoral response is important for characterizing the titer kinetics of children over time because of the evidence of waning immunity over time after immunization against hepatitis B, tetanus, influenza and other infectious diseases.Citation48,Citation66–69 The decrease of seroprotection was ascribed to the destruction of memory T cells during HIV disease progression in contrast to immune development in uninfected children, where the proportion of memory T cells rises with age, providing a more sustained serological response.

There was no difference in seroconversion between children belonging to the CDC category A, B or N than children belonging to CDC category C. Both live attenuated and recombinant/inactivated vaccines gave more systemic than local reactions with more than one adverse event reported per person.

The reactions are generally mild-to-moderate, with only three severe adverse events reported in adults (3/464, 0.64%) after a single dose of live attenuated VZV vaccine (ZVL) (retinal necrosis, and aseptic meningitis) and after 2 doses of ZVL (disseminated vaccine-strain VZV infection, respiratory failure and sepsis), and one case of severe neutropenia reported in children (1/224, 0.44%).

Our study evidenced a gap in the clinical studies aimed to analyze the immunogenicity of VZV vaccines in children because most of them are old and no studies on the efficacy of these vaccines in preventing VZV in CLWH have been found. Analogously, data on live attenuated VZV vaccination in ALWH are limited, which is in part due to the advice to not use live vaccines in these categories of subjects. Then, since recombinant ZV vaccine was licensed recently for the use in immunocompromised patients, further studies are needed to evaluate immunogenicity, safety and clinical efficacy of both live and recombinant zoster vaccines in ALWH.

Therefore, in this review, we could not evaluate the vaccine efficacy, due to the lack of data in literature, for the prevention of HZ and HZ-related complications in PLWH as disseminated infection, stroke or ischemic events.Citation70–72

Few studies reported on recurrent zoster and data were not enough to assess risk in immunocompromised subjects. Disseminated zoster was the most common studied among complications, but most assessments have been made from studies in hematopoietic transplants.

However, it was recently found that VZV reactivation is associated with an increased vascular risk in PLWH.Citation72

Beyond gaps in reporting the role of vaccinations in preventing complications of HZ, our review presents other limitations. Studies reviewed included only ALWH who generally had high baseline CD4 counts and excellent virologic control on ART, with limited characterization of patients with CD4 <200 cells/mm3; the results are therefore not generalizable to the entire ALWH population.

Most of the studies were from USA, with only two studies from Europe and two from Asia, with no information from countries with a high burden of HIV such as Africa.

Then, some subpopulatons of PLWH were not included, such as PLWH with coinfections and/or comorbidities, which may play a role in influencing the immunologic outcome.

There was important heterogeneity including study design, methods, and reporting (vaccine types, sample sizes, inclusion of a control group, interval between doses, postvaccination observation period and different immune response measurement).

Furthermore, the clinical, methodological, and statistical heterogeneity of the included studies in the absence of methods to assess the risk of bias or certainty in the body of evidence restricted our review to descriptive analysis perhaps affecting the robustness, and reliability of the findings.

In conclusion, although this systematic literature review was limited by the scarce quantity of literature, we show that RZV/ZVL are immunogenic, and have an acceptable safety profile in adults and children living with HIV.

Our review, therefore, should support healthcare professionals working with PLWH in evaluating the benefits versus risks of RZV vaccination in each individual, in an effort to prevent HZ disease and HZ-related burden of illness through vaccination.

Future studies that will include a great number of PLWH of different ages, genders, demographic settings, different countries, ART statuses and regimens, different viral loads, CD4 count stratification, coinfections, and comorbidities will be important for giving more reliable information on vaccine effectiveness and the durability of immune responses.

Author contributions

MADF and EQR were responsible for conceptualization and search design. MADF supervised the study. VC, LM, GT and EF were responsible for screening, data extraction, quality assessment and interpretation. MADF, VL, LM, GT prepared the first draft. All the Authors reviewed and revised the manuscript, and approved the final manuscript as submitted.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.

References

  • Gabutti G, Bolognesi N, Sandri F, Florescu C, Stefanati A. Varicella zoster virus vaccines: an update. Immunotargets Ther. 2019;8:15–16. doi:10.2147/ITT.S176383.
  • Gershon AA, Breuer J, Cohen JI, Cohrs RJ, Gershon MD, Gilden D, Grose C, Hambleton S, Kennedy PGE, Oxman MN, et al. Varicella zoster virus infection. Nat Rev Dis Primers. 2015;1(1):15016. doi:10.1038/nrdp.2015.16.
  • Abendroth A, Arvin AM, Moffat JF. Varicella-zoster virus. Springer Science & Business Media; 2010.
  • Marin M, Guris D, Chaves SS, Schmid S, Seward JF. Prevention of varicella: recommendations of the Advisory Committee on Immunization Practice (ACIP). Vol. 56, MMWR Recomm Rep; 2007. pp. 1–40.
  • World Health Organization. Varicella and herpes zoster vaccines: WHO position Paper. Wkly Epidemiol Rec. 2014;25:265.
  • Gabutti G, Franchi M, Maniscalco L, Stefanati A. Varicella-zoster virus: pathogenesis, incidence patterns and vaccination programs. Minerva Pediatr. 2016;68:213–25.
  • Corti M, Trione N, Villafane MF, Risso D, Yampolsky C, Mamanna L. Acute meningoencephalomyelitis due to varicella-zoster virus in an AIDS patient: report of a case and review of the literature. Rev Soc Bras Med Trop. 2011;44(6):784–6. doi:10.1590/S0037-86822011000600026.
  • Lechiche C, Le Moing V, Perrigault PF, Reynes J. Fulminant varicella hepatitis in a human immunodeficiency virus infected patient: case report and review of the literature. Scand J Infect Dis. 2006;38(10):929–31. doi:10.1080/00365540600561785.
  • Popara M, Pendle S, Sacks L, Smego RA, Mer M. Varicella pneumonia in patients with HIV/AIDS. Int J Infect Dis. 2002;6(1):6–8. doi:10.1016/S1201-9712(02)90128-1.
  • Levin MJ, Gershon AA, Weinberg A, Blanchard S, Nowak B, Palumbo P, Chan CY, AIDS Clinical Trials Group 265 Team. Immunization of HIV-infected children with varicella vaccine. J Pediatr. 2001;139(2):305–10. doi:10.1067/mpd.2001.115972.
  • Centers for Disease Control and Prevention. 1994 revised guidelines for the performance of CD4+ T-cell determinations in persons with human immunodeficiency virus (HIV) infections. MMWR Recomm Rep. 1994;43:1–21.
  • Levin MJ, Gershon AA, Weinberg A, Song LY, Fentin T, Nowak B. Administration of live varicella vaccine to HIV-Infected children with current or past significant depression of CD4 + T Cells. J Infect Dis. 2006;194(2):247–55. doi:10.1086/505149.
  • Bekker V, Scherpbier H, Pajkrt D, Jurriaans S, Zaaijer H, Kuijpers TW. Persistent humoral immune defect in highly active antiretroviral therapy–treated children with HIV-1 infection: loss of specific antibodies against attenuated vaccine strains and natural viral infection. Pediatrics. 2006;118(2):315–22. doi:10.1542/peds.2005-2616.
  • Ludwig B, Kraus FB, Allwinn R, Keim S, Doerr HW, Buxbaum S. Loss of varicella zoster virus antibodies despite detectable cell mediated immunity after vaccination. Infection. 2006;34(4):222–6. doi:10.1007/s15010-006-5616-9.
  • Weinberg A, Lazar AA, Zerbe GO, Hayward AR, Chan ISF, Vessey R, Silber JL, MacGregor RR, Chan K, Gershon AA, et al. Influence of age and nature of primary infection of varicella zoster virus-specific cell-mediated immune responses. J Infect Dis. 2010;201(7):1024–30. doi:10.1086/651199.
  • Solomon CG, Cohen JI. Hepes zoster. N Engl J Med. 2013;369(3):255–63. doi:10.1056/NEJMcp1302674.
  • Yanni EA, Ferreira G, Guennec M, El Hahi Y, El Ghachi A, Haguinet F, Espie E, Bianco V. Burden of herpes zoster in 16 selected immunocompromised populations in England: a cohort study in the clinical practice research datalink 2000–2012. BMJ Open. 2018;8(6):e020528. doi:10.1136/bmjopen-2017-020528.
  • Johnson RW, Levin MJ. Herpes zoster and its prevention by vaccination. Interdiscip Top Gerontol Geriatr. 2020;43:131–45.
  • Forbes HJ, Bhaskaran K, Thomas SL, Smeeth L, Clayton T, Langan SM. Quantification of risk factors for herpes zoster: population-based case-control study. BMJ. 2014;348:g2911. doi:10.1136/bmj.g2911.
  • Schmader K. Herpes zoster. Ann Intern Med. 2018;169(3):19–31. ITC.
  • Tseng HF, Bruxvoort K, Ackerson B, Luo Y, Tanenbaum H, Tian Y, Zheng C, Cheung B, Patterson BJ, Van Oorschot D, et al. The epidemiology of herpes zoster in immunocompetent, unvaccinated adults ≥50 years old: incidence, complications, hospitalization, mortality, and recurrence. J Infect Dis. 2020;222(5):798–806. doi:10.1093/infdis/jiz652.
  • Mbinta JF, Nguyen BP, Awuni PMAA, Eme PE, Simpson CR. Postlicensure herpes zoster vaccine effectiveness: systematic review protocol. BMJ Open. 2021;11(2):e040964. doi:10.1136/bmjopen-2020-040964.
  • Chen SY, Suaya JA, Li Q, Galindo CM, Misurski D, Burstin S, Levin MJ. Incidence of herpes zoster in patients with altered immune function. Infection. 2014;42(2):325–34. doi:10.1007/s15010-013-0550-8.
  • Munoz-Quiles C, Lopez-Lacort M, Diez-Domingo J, Orrico-Sanchez A. Herpes zoster risk and burden of disease in immunocompromised populations: a population-based study using health system integrated databases, 2009–2014. BMC Infect Dis. 2020;20(1):905. doi:10.1186/s12879-020-05648-6.
  • Rommelaere M, Maréchal C, Yombi JC, Goffin E, Kanaan N. Disseminated varicella zoster virus infection in adult renal transplant recipients: outcome and risk factors. Transplant Proc. 2012;44(9):2814–7. doi:10.1016/j.transproceed.2012.09.090.
  • Lachiewicz AM, Srinivas ML. Varicella-zoster virus post-exposure management and prophylaxis: a review. Prev Med Rep. 2019;16:101016. doi:10.1016/j.pmedr.2019.101016.
  • Moanna A, Rimland D. Decreasing incidence of herpes zoster in the highly active antiretroviral therapy era. Clin Infect Dis. 2013;57(1):122–5. doi:10.1093/cid/cit165.
  • McKay SL, Guo A, Pergam SA, Dooling K. Herpes zoster risk in immunocompromised adults in the United States: a systematic review. Clin Infect Dis. 2020;71(7):125–34. doi:10.1093/cid/ciz1090.
  • Gilbert L, Wang X, Deiss R, Okulicz J, Maves R, Schofield C, Ferguson T, Whitman T, Kronmann K, Agan B, et al. Herpes zoster rates continue to decline in people living with human immunodeficiency virus but remain higher than rates reported in the general US population. Clin Infect Dis. 2019;69(1):155–8. doi:10.1093/cid/ciy1041.
  • Grabar S, Tattevin P, Selinger-Leneman H, de La Blanchardiere A, de Truchis P, Rabaud C, Rey D, Daneluzzi V, Ferret S, Lascaus AS, et al. Incidence of herpes zoster in HIV-infected adults in the combined antiretroviral therapy era: results from the FHDH-ANRS CO4 cohort. Clin Infect Dis. 2015;60(8):1269–77. doi:10.1093/cid/ciu1161.
  • Blank LJ, Polydefkis MJ, Moore RD, Gebo KA. Herpes zoster among persons living with HIV in the current antiretroviral therapy era. J Acquir Immune Defic Syndr. 2012;61(2):203–7. doi:10.1097/QAI.0b013e318266cd3c.
  • Pathai S, Bajillan H, Landay AL, High KP. Is HIV a model of accelerated or accentuated aging? J Gerontol A Biol Sci Med Sci. 2014;69(7):833–42. doi:10.1093/gerona/glt168.
  • Smit M, Brinkman K, Geerlings S, Smit C, Thyagarajan K, van Sighem A, de Wolf F, Hallett TB. Future challenges for clinical care of an ageing population infected with HIV: a modelling study. Lancet Infect Dis. 2015;15(7):810–8. doi:10.1016/S1473-3099(15)00056-0.
  • Lagathu C, Cossarizza A, Béréziat V, Nasi M, Capeau J, Pinti M. Basic science and pathogenesis of ageing with HIV: potential mechanisms and biomarkers. AIDS. 2017;31(Supplement 2):105–19. doi:10.1097/QAD.0000000000001441.
  • Erdmann NB, Prentice HA, Bansal A, Wiener HW, Burkholder G, Shrestha S, Tang J. Herpes zoster in persons living with HIV-1 infection: Viremia and immunological defects are strong risk factors in the Era of combination antiretroviral therapy. Front Public Health. 2018;6:70. doi:10.3389/fpubh.2018.00070.
  • Segal BH. Management of infections in the immunocompromised host. 1. Switzerland: Springer International Publishing; 2018.
  • Dooling KL, Guo A, Patel M, Lee GM, Moore K, Belongia EA, Harpaz R. Recommendations of the Advisory Committee on immunization practices for use of herpes zoster vaccines. MMWR Morb Mortal Wkly Rep. 2018;67(3):103–8. doi:10.15585/mmwr.mm6703a5.
  • De Oliveira Gomes J, Gagliardi AMZ, Andriolo BNG, Torloni MR, Andriolo RB, Dos Santos Puga ME, Canteiro CE. Vaccines for preventing herpes zoster in older adults. Cochrane Database Syst Rev. 2023;10(10). doi:10.1002/14651858.CD008858.pub5. CD008858.
  • Kucharzik T, Ellul P, Greuter T, Rahier JF, Verstockt B, Abreu C, Albuquerque A, Allocca M, Esteve M, Farraye FA, et al. ECCO guidelines on the prevention, diagnosis, and management of infections in inflammatory bowel disease. J Crohns Colitis. 2021;15(6):879–913. doi:10.1093/ecco-jcc/jjab052.
  • GlaxoSmithKline. Shingrix EU Summary of Product Characteristics (SmPC). Updated March 2021.
  • GlaxoSmithKline. Shingrix US Prescribing Information (PI). Revised August 2021
  • Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, Shamseer L, Tetzlaff JM, Akl EA, Brennan SE, et al. The PRISMA 2020 statement: an update guideline for reporting systematic reviews. BMJ. 2021;372:n71. doi:10.1136/bmj.n71.
  • Mullane KM, Winston DJ, Wertheim MS, Betts RF, Poretz DM, Camacho LH, Pergan SA, Mullane MR, Stek JE, Sterling TM, et al. Safety and immunogenicity of heat-treated zoster vaccine (ZVHT) in immunocompromised adults. J Infect Dis. 2013;208(9):1375–85. doi:10.1093/infdis/jit344.
  • Benson CA, Andersen JW, Macatangav BJC, Mailliard RB, Rinaldo CR, Read S, Bozzolo DR, Purdue L, Jennings C, Keefer MC, et al. Safety and immunogenicity of zoster vaccine live in human immunodeficiency virus–infected adults with CD4+ cell counts >200 cells/mL virologically suppressed on antiretroviral therapy. Clin Infect Dis. 2018;67(11):1712–19. doi:10.1093/cid/ciy242.
  • Berkowitz EM, Moye G, Stellbrink HJ, Schurmann D, Kegg S, Stoll M, El Idrissi M, Oostvogels L, Heineman TC, Brockmeyer N, et al. Safety and immunogenicity of an adjuvanted herpes zoster subunit candidate vaccine in HIV-infected adults: a phase 1/2a randomized, placebo-controlled study. J Infect Dis. 2015;211(8):1279–87. doi:10.1093/infdis/jiu606.
  • Weinberg A, Levin MJ, MacGregor RR. Safety and immunogenicity of a live attenuated varicella vaccine in VZV-seropositive HIV-infected adults. Hum Vaccin. 2010;6(4):318–21. doi:10.4161/hv.6.4.10654.
  • Taweesith W, Puthanakit T, Kowitdamrong E, Bunipuradh T, Wongngam W, Phasimsap C, Aprnpong T, Bouko C, Pancharoen C. Varicella-zoster virus vaccine in human immunodeficiency virus-infected children. Pediatr Infect Dis J. 2011;30(4):320–4. doi:10.1097/INF.0b013e3181fe0868.
  • Bekker V, Westerlaken GHA, Scherpbier H, Alders S, Zaaijer H, van Baarle D, Kujpers T. Varicella vaccination in HIV-1 infected children. AIDS. 2006;20(18):2321–9. doi:10.1097/QAD.0b013e3280113f29.
  • Armenian SH, Han JY, Dunaway TM, Church JA. Safety and immunogenicity of live varicella virus vaccine in children with human immunodeficiency virus type 1. Pediatr Infect Dis J. 2006;25(4):368–70. doi:10.1097/01.inf.0000207492.97867.15.
  • Gershon AA, Levin MJ, Weinberg A, Song LY, LaRussa PS, Steinberg SP, Bartlett P. A phase i–ii study of live attenuated varicella-zoster virus vaccine to boost immunity in human immunodeficiency virus-infected children with previous varicella. Pediatr Infect Dis J. 2009;28(7):653–5. doi:10.1097/INF.0b013e3181998f06.
  • Purswani MU, Karalius B, Yao TJ, Schmid DS, Burchett SK, Siberry GK, Patel K, Van Dyke RB, Yogev R. Prevalence and persistence of varicella antibodies in previously immunized children and youth with perinatal HIV-1 infection. Clin Infect Dis. 2016;62(1):106–14. doi:10.1093/cid/civ734.
  • Navalkele BD, Henig O, Fairfax M, Flanagan E, Upfal M, Russell J, Dhr S, Kaye K, Chopra T. First case of vaccine-strain varicella infection as manifestation of HIV in healthcare worker: a case report and review of the literature. J Hosp Infect. 2017;97(4):384–8. doi:10.1016/j.jhin.2017.05.024.
  • Maves RC, Trippa MS, Dell TG, Bennett JW, Ahluwalia JS, Tamming C, Bldwinh JC, Starr CR, Grinkemeyer MD, Dempseya MP. Disseminated vaccine-strain varicella as initial presentation of the acquired immunodeficiency syndrome: a case report and review of the literature. J Clin Virol. 2014;59(1):63–6. doi:10.1016/j.jcv.2013.10.027.
  • Su JR, Ng C, Lewis PW, Cano MV, Crawford NW. Adverse events after vaccination among HIV-positive persons, 1990–2016. PLOS ONE. 2018;13(6):e0199229. doi:10.1371/journal.pone.0199229.
  • Martino FK, Pini S, Scaparrotta G, Schirinzi M, Gnappi M, Fragasso A, Zanella R, Naso E, De Giorgi ML, Carraro G, et al. Recombinant varicella zoster vaccine in haemodialysis facilities: adherence and safety. J Nephrol. 2023;36(7):2155–8. doi:10.1007/s40620-023-01690-0.
  • Lasagna A, Mele D, Bergami F, Alaimo D, Dauccia C, Alessio N, Comolli G, Pasi F, Muzzi A, Novelli V, et al. The immunogenicity and the safety of the adjuvanted glycoprotein E (gE)-based recombinant vaccine against herpes zoster (RZV) in cancer patients during immunotherapy. Hum Vaccin Immunother. 2023;19(3):2288282. doi:10.1080/21645515.2023.2288282.
  • Mwakingwe-Omari A, Lecrenier N, Naficy A, Curran D, Posiuniene I. Recombinant zoster vaccine in immunocompetent and immunocompromised adults: A review of clinical studies. Hum Vaccin Immunother. 2023;19(3):2278362. doi:10.1080/21645515.2023.2278362.
  • Anderson TC, Masters NB, Guo A, Shepersky L, Leidner AJ, Lee GM, Kotton CN, Dooling KL. Use of recombinant zoster vaccine in immunocompromised adults aged ≥19 years: recommendations of the advisory committee on immunization practices - United States, 2022. MMWR Morb Mortal Wkly Rep. 2022;71(3):80–4. doi:10.15585/mmwr.mm7103a2.
  • Bastidas A, de la Serna J, El Idrissi M, Oostvogels L, Quittet P, López-Jiménez J, Vural F, Pohlreich D, Zuckerman T, Issa NC, et al. Effect of recombinant zoster vaccine on incidence of herpes zoster after autologous stem cell transplantation: a randomized clinical trial. JAMA. 2019;322(2):123–33. doi:10.1001/jama.2019.9053.
  • Dagnew AF, Ilhan O, Lee WS, Woszczyk D, Kwak JY, Bowcock S, Sohn SK, Rodriguez MacíMacíAs G, Chiou TJ, Quiel D, et al. Immunogenicity and safety of the adjuvanted recombinant zoster vaccine in adults with haematological malignancies: a phase 3, randomised, clinical trial and post-hoc efficacy analysis. Lancet Infect Dis. 2019;19(9):988–1000. doi:10.1016/S1473-3099(19)30163-X.
  • Vink P, Delgado Mingorance I, Maximiano Alonso C, Rubio-Viqueira B, Jung KH, Rodriguez Moreno JF, Grande E, Marrupe Gonzalez D, Lowndes S, Puente J, et al. Immunogenicity and safety of the adjuvanted recombinant zoster vaccine in patients with solid tumors, vaccinated before or during chemotherapy: a randomized trial. Cancer. 2019;125(8):1301–12. doi:10.1002/cncr.31909.
  • Koldehoff M, Horn PA, Lindemann M. Cellular immune response after vaccination with an adjuvanted, recombinant zoster vaccine in allogeneic hematopoietic stem cell transplant recipients. Vaccines. 2022;10(5):809. doi:10.3390/vaccines10050809.
  • Lal H, Cunningham AL, Godeaux O, Chlibek R, Diez-Domingo J, Hwang SJ, Levin MJ, McElhaney JE, Poder A, Puig-Barberà J, et al. Efficacy of an adjuvanted herpes zoster subunit vaccine in older adults. N Engl J Med. 2015;372(22):2087–96. doi:10.1056/NEJMoa1501184.
  • Levin MJ, Kroehl ME, Johnson MJ, Hammes A, Reinhold D, Lang N, Weiberg AA. Th1 memory differentiates recombinant from live herpes zoster vaccines. J Clin Invest. 2018;128(10):4429–40. doi:10.1172/JCI121484.
  • Johnson MJ, Liu C, Ghosh D, Lang N, Levin MJ, Weinberg A. Cell mediated immune responses after administration of the live or the recombinant zoster vaccine: 5-year persistence. J Infect Dis. 2022;225(8):1477–81. doi:10.1093/infdis/jiab580.
  • Siriaksorn S, Puthanakit T, Sirisanthana T, Sirisanthana V. Prevalence of protective antibody against hepatitis B virus in HIV-infected children with immune recovery after highly active antiretroviral therapy. Vaccine. 2006;24(16):3095–9. doi:10.1016/j.vaccine.2006.01.045.
  • Sutcliffe CG, Moss WJ. Do children infected with HIV receiving HAART need to be revaccinated? Lancet Infect Dis. 2010;10(9):630–42. doi:10.1016/S1473-3099(10)70116-X.
  • Menson EN, Mellado MJ, Bamford A, Castelli G, Duiculescu D, Marczynska M, Navarro ML, Scherpbier HJ, Heath PT. Guidance on vaccination of HIV-infected children in Europe. HIV Med. 2012;13(6):333–6. doi:10.1111/j.1468-1293.2011.00982.x.
  • Crum-Cianflone NF, Iverson E, Defang G, Blair PJ, Eberly LE, Maguire J, Ganesan A, Faix D, Duplessis C, Lalan T, et al. Durability of antibody responses after receipt of the monovalent 2009 pandemic influenza a (H1N1) vaccine among HIV-infected and HIV-uninfected adults. Vaccine. 2011;29(17):3183–91. doi:10.1016/j.vaccine.2011.02.040.
  • Zeng L, Feng S, Yao L, Zhao J, Zhang G. Disseminated herpes zoster with decreased CD4 counts in a HIV-Infected patient. Clin Cosmet Investig Dermatol. 2023;16:3165–70. doi:10.2147/CCID.S429308.
  • Ku HC, Wu YL, Yip HT, Hsieh CY, Li CY, Ou HT, Chen YC, Ko NY. Herpes zoster associated with stroke incidence in people living with human immunodeficiency virus: a nested case–control study. BMC Infect Dis. 2023;23(1):636. doi:10.1186/s12879-023-08628-8.
  • Fiordelisi D., Poliseno M., De Gennaro N., Milano E., Santoro CR., Segala FV., Franco CF., Manco Cesari G., Frallonardo L., Guido G. et al. Varicella-zoster virus reactivation and increased vascular risk in people living with HIV: Data from a retrospective cohort study. Viruses. 2023;15(11):2217. doi:10.3390/v15112217.
Download PDF

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.