Vacunación contra la hepatitis B para la reducción de la morbilidad y la mortalidad en pacientes con infección por VIH
Resumen
Antecedentes
Se ha recomendado el uso de la vacuna contra la hepatitis B en los pacientes que viven con VIH (PVVIH), debido principalmente a las similitudes en las vías de infección y su prevalencia en las mismas zonas geográficas. Es posible que los PVVIH no desarrollen seroprotección después de recibir la vacuna estándar contra la hepatitis B debido al compromiso de su estado inmunológico.
Objetivos
Evaluar la eficacia de la vacuna contra el virus de la hepatitis B en PVVIH en comparación con placebo o ninguna vacuna.
Métodos de búsqueda
Se hicieron búsquedas en seis bases de datos en inglés en julio de 2012 y se actualizó la búsqueda en junio de 2013 y agosto de 2014. Se realizaron búsquedas en la literatura gris, actas de congresos, sitios web especializados, y se estableció contacto con expertos en el tema.
Criterios de selección
Ensayos controlados aleatorios de la vacuna contra la hepatitis B en comparación con placebo o ninguna vacuna que evaluaran resultados relevantes de eficacia y seguridad.
Obtención y análisis de los datos
Dos revisores de forma independiente buscaron y extrajeron los datos sobre el diseño de los estudios, los participantes, la infección por hepatitis B, la morbilidad y la mortalidad relacionadas con la hepatitis B, la inmunogenicidad anti‐HB y los efectos adversos relacionados con las vacunas a partir de artículos publicados o mediante la correspondencia con autores. Los datos se analizaron cualitativamente.
Resultados principales
En esta revisión se incluyó un ensayo controlado aleatorio doble ciego con 26 participantes que recibían tratamiento antirretroviral (TAR), realizado en España, que comparó la vacuna contra la hepatitis B con placebo y cumplió los criterios de elegibilidad. El estudio duró tres años y los pacientes se siguieron mensualmente. El estudio informó una respuesta humoral adecuada a la vacuna a los 12 meses y ningún efecto secundario local o sistémico en los grupos de intervención y control. Esta respuesta humoral se perdió cuando los participantes dejaron de tomar el TAR. El tamaño de la muestra del estudio fue pequeño y el estudio se realizó en un ámbito de ingresos altos, a diferencia de las áreas con carga más alta de hepatitis B y coinfecciones por VIH.
Conclusiones de los autores
Las pruebas de este estudio no son suficientes para apoyar cualquier recomendación con respecto al uso de la vacuna contra la hepatitis B en PVVIH. Estas pruebas tampoco demuestran que la vacuna contra la hepatitis B no sea segura en los PVVIH. Se necesitan ensayos controlados aleatorios adicionales en áreas con alta prevalencia que generen pruebas sobre la eficacia y la seguridad a largo plazo de la vacuna contra la hepatitis B en PVVIH con y sin TAR. También se deben explorar diferentes regímenes y vías de administración.
PICO
Resumen en términos sencillos
Vacuna contra el virus de la hepatitis B para pacientes que viven con infección por el VIH/SIDA
Pregunta de estudio
Esta revisión intenta determinar si la vacuna contra el virus de la hepatitis B es eficaz para proteger a los pacientes que tienen VIH contra la infección por el virus de la hepatitis B. También intenta determinar si la vacuna es segura en los pacientes que viven con VIH.
Antecedentes
La infección por el virus de la hepatitis B se puede adquirir a través del contacto con líquidos corporales de pacientes infectados. La infección por el virus de la hepatitis B se manifiesta con fiebre, amarillez de los ojos, dolor abdominal y fatiga, pero también puede presentarse sin síntomas, especialmente en infecciones de larga duración. Puede causar una infección persistente que puede provocar complicaciones hepáticas y muerte. La infección por el virus de la hepatitis B y la infección por VIH son frecuentes en los países más pobres y en estos países las vacunas no están fácilmente disponibles. Es posible que los pacientes que viven con VIH no respondan bien a la infección por el virus de la hepatitis B debido a la débil capacidad de sus cuerpos para desarrollar resistencia.
Características de los estudios
La búsqueda de artículos elegibles se actualizó en agosto de 2014 y se encontró un ensayo con 26 participantes adultos en España. El estudio se propuso probar si la vacuna contra el virus de la hepatitis B fue mejor que placebo para evitar que los PVVIH adquirieran la hepatitis B.
Resultados clave
El único estudio en esta revisión mostró mejor inmunidad contra la hepatitis B a los 12 meses entre los pacientes que vivían con VIH y recibían tratamiento antirretroviral. Esta inmunidad se perdió una vez que dejaron de tomar el tratamiento antirretroviral. No se informaron efectos secundarios.
Calidad de la evidencia
La calidad de las pruebas se evaluó como muy baja.
Authors' conclusions
Summary of findings
| Hepatitis B vaccination compared to placebo for reducing morbidity and mortality in persons with HIV infection | ||||||
| Patient or population: Persons with HIV infection | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | No of Participants | Quality of the evidence | Comments | |
| Assumed risk | Corresponding risk | |||||
| Control | Hepatitis B vaccination compared to placebo | |||||
| Hepatitis B Virus infection ‐ not measured | See comment | See comment | Not estimable | ‐ | See comment | |
| Hepatitis B virus morbidity ‐ not measured | See comment | See comment | Not estimable | ‐ | See comment | |
| Hepatitis B virus related mortality ‐ not measured | See comment | See comment | Not estimable | ‐ | See comment | |
| All cause mortality ‐ not measured | See comment | See comment | Not estimable | ‐ | See comment | |
| Hepatitis B antibody titre (IgG) | The median IgG titre in the control group was | The median IgG titre in the intervention group was | Not estimable | 25 | ⊕⊝⊝⊝ | Authors report "Statistically significant (P<0.05) difference between groups using the Mann–Whitney U‐test for comparison." |
| *The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1 Randomisation and allocation concealment not described | ||||||
Background
Hepatitis B virus (HBV) infection affects about 2 billion people worldwide, with about 350 million people living with chronic infection. An estimated 600,000 persons die each year due to acute or chronic consequences of hepatitis B virus infection (WHO 2008). A total of 35.5 million people were living with Human Immunodeficiency Virus (HIV) in 2007, and 22.5 million of these were living in Sub Saharan Africa (UNAIDS 2013). Due to the shared routes of transmission, co‐infection with HIV and HBV is common, ranging from 20% in high HBV endemic areas to 5% in areas of low endemicity (Lee 2008; Diop‐Ndiaye 2008; Nyirenda 2008; Alter 2006). Immunosuppressed patients have been shown to have a reduced antibody response following HBV vaccination (Miller 2012; Siriaksorn 2006). They are also less likely to maintain high protective antibody levels compared to immunocompetent individuals (McQuillan 2010). Lack of adequate adjuvancy ‐ an appropriate immune response ‐ may explain the lack of vaccine immunogenicity in immunosuppressed individuals (Angel 2008). Adjuvants can be added to vaccines to boost the immune response. These Adjuvant Systems, when added to recombinant protein antigens, can be fundamental in developing effective prophylactic vaccines against complex pathogens, e.g. clostridium, HIV infection and mycobacterium and vaccines against complex diseases, e.g. malaria, HIV infection and tuberculosis, and for special target populations such as subjects with an impaired immune response, due to age or medication (Vandepapelière 2008).
Description of the condition
The hepatitis B virus attacks the liver and can cause chronic or acute infection. Infected individuals manifest symptoms that may last several weeks. These include fever, jaundice, fatigue, nausea, vomiting and abdominal pain. People who get HBV infection earlier in their lives are more likely to develop a chronic infection. Just like HIV, it is transmitted through contact with blood or other bodily fluids from an infected person (WHO 2008). Co‐infection of HBV and HIV results in a greater morbidity and mortality. These patients may also present with higher rates of ART‐related hepatotoxicity and poorer immunologic outcomes (BHIVA 2004; BHIVA 2010). There are close to 350 million HBV carriers worldwide (BHIVA 2004; BHIVA 2010).
Description of the intervention
HBV infection can be prevented with a 3 dose‐vaccine which induces protective antibody levels in more than 95% of infants, children and young adults. Vaccination is considered the best method of prevention against hepatitis B virus and following complete immunisation, an adequate response will develop immunogenicity levels of anti‐HBS antibodies greater than 10 mIU/ml (Behairy 2009). Despite advances in ART therapy, only a minority of patients with chronic hepatitis B will have a sustained humoral response. Therefore, primary prevention through vaccination to increase herd immunity remains the main thrust in the control of HBV infection. Currently available hepatitis B vaccines are safe, have an efficacy of more than 95% and are effective against all HBV serotypes and genotypes (WHO 2011).
How the intervention might work
Immunogenic response to HBV vaccine may vary in people already infected with HIV, it may also vary when immunized persons get infected with HIV and may vary in those on ART compared to the ART‐naive. However, HBV vaccination can significantly reduce infection with HBV and thus reduce the co‐infectivity of HBV/HIV, by reducing the chances of people living with HIV (PLHIV) getting infected with the HBV virus.
Why it is important to do this review
This review seeks to answer whether vaccination against HBV for people with HIV will contribute to reducing morbidity and mortality, and improving quality of life. There are several studies suggesting different options for vaccination against HBV in immunocompromised persons including PLHIV (ART initiation, double dosing ‐quantity and frequency, and the use of adjuvants); however, there is insufficient evidence on what to do with respect to HBV vaccination for PLHIV even though the people at risk of acquiring HIV are also at risk of acquiring HBV. In addition, with HIV infection there has been reported sub optimal immune response to vaccination (BHIVA 2004; BHIVA 2008; BHIVA 2010; McQuillan 2010). Some studies also suggest that lower levels of immunity would be achieved if they were vaccinated prior to ART. A review of the current evidence will therefore help to guide decision‐making with respect to improved outcomes and highlight avenues for research.
Objectives
To assess the efficacy of HBV vaccination in preventing hepatitis B virus infection and its consequences among PLHIV.
Methods
Criteria for considering studies for this review
Types of studies
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We considered randomised controlled trials of hepatitis B vaccination against no vaccine or placebo.
Types of participants
We considered trials with adults and children infected with HIV confirmed by ELISA (Enzyme Linked Immuno Sorbent Assay); irrespective of whether they are on ART or not. All stages of disease were included. Trials with PLHIV who were already infected with HBV were excluded from the study owing to the inability to determine changes in serology. Trials with PLHIV whose HBV status was unknown were also be excluded from the study.
Types of interventions
We considered all vaccinations against HBV including the single dose regimens. We compared these interventions against placebo or no vaccination. Trials with individuals who did not complete the immunisations were excluded. We did not consider multidose regimens, the use of adjuvants and combination interventions.
Types of outcome measures
Primary outcomes
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Infection with HBV: For this outcome we intended to measure the incidence of HBV based on the presence of the HBV surface markers (HbSAg, HBcAg) and/or HBV nucleic acids in a cohort of PLHIV known to be previously not infected with HBV.
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Hepatitis B related morbidity: We intended to measure the proportions of individuals with HBV related morbidity over the time frames defined by the authors. We intended to include liver cirrhosis, hepatic failure and primary liver cell carcinomas.
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Hepatitis B related mortality: We intended to measure the proportions of individuals who died subsequent to liver failure.
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All cause mortality
Secondary outcomes
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Levels of immunogenicity following vaccination (anti‐HBs antibodies greater than 10mIU/ml was considered adequate levels of immunogenicity following vaccination)
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Adverse effects related to HBV vaccine: We considered all the adverse events as reported by the authors.
Search methods for identification of studies
We worked with the Cochrane HIV/AIDS Review Group Trials Search coordinator to assist with the search and identify studies to be included in the review. We systematically developed a comprehensive and exhaustive search strategy which helped us to identify all relevant studies. We included all relevant studies without bias of language or publication status (published, unpublished, in press or in progress). Study authors were contacted when the information in the retrieved manuscripts was incomplete or unclear.
Electronic searches
We searched the following electronic databases and conference proceedings:
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The Cochrane Central Register of Controlled Trials (1981‐August 2014) and the Cochrane Hepato‐Biliary Group ControlledTrials Register (1981‐August 2014) via the Cochrane Library (CLIB)
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MEDLINE via PubMed (1981‐August 2014)
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EMBASE (1981‐August 2014)
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The WHO International Clinical Trials Registry Platform (1981‐August 2014)
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Clinicaltrials.gov (1981‐August 2014)
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AEGIS (AIDS Education Global Information System) which includes the following conferences:
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British HIV/AIDS Association, 2001‐2009
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Conference on Retroviruses and Opportunistic Infections (CROI), 1994‐2008
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European AIDS Society Conference, 2001 and 2003
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International AIDS Society, AIDS 1994‐2008
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International AIDS Society, Conference on HIV Pathogenesis, Treatment and Prevention (IAS), 2001‐2009
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US National HIV Prevention Conference, 1999, 2003, and 2005
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We searched for relevant studies from 1981 to August 2014. This timeline corresponds to the identification of the first case of HIV in the United States and also the time when the first recombinant Hepatitis B vaccine was produced. The search strategy included text terms such as Vaccination, immunisation, hepatitis B Virus, Hepatitis B Virus Vaccination, Hepatitis B Virus Immunisation, Human Immunodeficiency Virus, HIV, HBV, Engerix B, Recombivax HB, Elovac B, Genevac B, Shanvac B used in various combinations.
Searching other resources
We performed a handsearch of relevant reference lists of all pertinent reviews and studies found. We also contacted experts, authors, pharmaceutical industries and research organizations in the field for unpublished and on going studies.
Data collection and analysis
Selection of studies
Two authors (MPO and LM) critically appraised all the identified citations independently to establish the possible relevance of the articles for inclusion or exclusion and also to ensure they met the pre‐specified criteria for the review. Agreement was estimated using the Kappa statistic (Viera 2005). We reviewed studies for relevance based on type of study, trial participants, trials interventions, and outcome measures using a pre‐tested study eligibility form. We resolved any disagreement by discussion or by contacting an independent author for arbitration (SR/BN). Full text for potentially relevant manuscripts were obtained and screened. We gave reasons for excluding potentially relevant trials in a table of excluded studies (Excluded studies). Multiple results for the same study were investigated for inclusion or exclusion following pre‐specified criteria. The reviewers were not blinded to authors, journals or titles.
Data extraction and management
We developed and tested a data extraction form tailored to the review question and covering the review outcomes. We used the agreed upon data extraction form to extract data. Each author extracted data independently thereafter, authors verified each others extraction to arrive at a consensus. We included in our extraction, comprehensive information about each study such as:
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Source of data ( study ID, report ID, review author ID, citation and contact detail)
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eligibility (confirm if paper is eligible for review or not and specify reason for exclusion)
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Populations and settings (number of participants, setting, geographical location, diagnostic criteria, age, sex, co‐morbidity, ethnicity and date of publication)
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Methods (study design, total study duration, sequence generation, allocation sequence concealment, blinding, follow up and other concerns of bias)
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Interventions (total number of interventions, specific interventions, intervention details, and integrity of intervention)
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Outcomes (outcomes and time points ‐ collected and reported, outcome definition, unit of measurement and scales)
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Results (number of participants allocated to each intervention or control group, ‐ sample size, missing participants, summary of data, sub group analysis)
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Miscellaneous (funding source, key conclusions of study authors, correspondences, comments from authors and review authors)
In the event of multiple reports for same studies, we came to a consensus on how to handle the data before decision on a data collation strategy. We handled disagreements by discussion.
Assessment of risk of bias in included studies
The risk of bias was assessed independently by two review authors using the following key criteria:
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Sequence generation: how the allocation sequence was generated and whether it was adequate.
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Allocation concealment: how the allocation sequence was concealed and whether it was adequate.
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Blinding of participants, personnel, and outcome assessors.
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The description of the completeness of outcome data for each main outcome.
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Selective outcome reporting. We verified that all expected and relevant outcomes were reported.
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Other potential threats of reliability
We assessed the risk of bias of the trials and classified them as adequate, inadequate or unclear as per the Cochrane Handbook of Systematic Reviews of Interventions (Higgins 2008).
Assessment of the quality of the body of evidence
We assessed the quality of the body of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE; Guyatt 2008) tool. The quality rating across studies has four levels: high, moderate, low and very low.
Measures of treatment effect
We planned to analyse data using Review Manager (Revman 2008) for statistical analysis. The standard methods of the Cochrane HIV/AIDS Review Group were used to synthesize data (Higgins 2008). We planned to calculate the median and interquartile range (IQR) or means and standard deviations (SD) for quantitative variables and numbers and percentages for categorical variables, alongside 95 % confidence intervals.
Unit of analysis issues
No cluster RCTs were included in this review.
Dealing with missing data
We contacted authors for missing data. In case we did not get a response from an author, we considered that incomplete outcome data had been adequately addressed if 85% or more of the participants were included in the analysis, or if less than 85% were included but adequate steps were taken to ensure or demonstrate that this did not interfere with the outcomes. In cases where the above was not clear, we planned to perform an intention‐to‐treat analysis.
Assessment of heterogeneity
We planned to first assess studies for methodological and clinical heterogeneity. If studies were comparable enough to combine, a meta‐analysis was to be performed and statistical heterogeneity assessed. A random effects meta‐analysis would have been performed if there was statistical heterogeneity.
We also planned to explore possible sources of heterogeneity in this review which included type of HBV vaccine used (plasma derived vaccine or recombinant HBV vaccine, use of adjuvants or not ; ART medication being taken; threshold for detection of viral nucleic acids, drug dosage, and study design).
The impact of any statistical heterogeneity would have been quantified using the I² statistic (Higgins 2008). Where we were not able to combine data, we provided a narrative report.
Assessment of reporting biases
Publication bias was not assessed because minimal criteria for assessing publication bias were not met (Ioannidis 2007).
Data synthesis
We planned to carry out statistical analysis using the Review Manager software (Revman 2008), using fixed‐effect meta‐analysis for combining data where it was reasonable to assume that studies were estimating the same underlying treatment effect: that is, where trials were examining the same intervention, and the populations and methods of trials were judged sufficiently similar. In case there was clinical heterogeneity sufficient to expect that the underlying treatment effects differed between trials, or in case substantial statistical heterogeneity was detected, we planned to use random‐effects meta‐ analysis to produce an overall summary in case an average treatment effect across trials was considered clinically meaningful.
Subgroup analysis and investigation of heterogeneity
If there was heterogeneity and the data were available we planned to explore this by looking at the following subgroups: age (children/adolescents/adults), sex (male/ female), medication (drugs like Tenofovir, Lamuvudine and Emcitrabine are also potent against HBV (Levy 2006)), type of vaccine (protein derived vaccines/ recombinant DNA; DNA), ethnicity or race (Black/Caucasian/Hispanic etc.), HIV disease stage and study design.
Sensitivity analysis
A sensitivity analysis was planned to evaluate how robust our findings were for different study designs, type of vaccine used, and type of ART.
Results
Description of studies
See Characteristics of included studies; Characteristics of excluded studies; Characteristics of ongoing studies.
Results of the search
With the assistance of the Cochrane HIV/AIDS group trial search coordinator, we conducted a search on July 26, 2012 and updated on June 12, 2013 and again in August 2014. A total of 959 records were identified, after sorting and removal of 68 duplicate titles, a total of 894 titles were left (Figure 1). After review of titles and abstracts, 44 titles were short listed for further critical appraisal of full text . Only 1 paper met our inclusion criteria. (Castro 2009). All disagreements were resolved by discussion. Thirty‐three (33) papers were also identified as on‐going trials. Studies were included based on design, types of participants, interventions and outcomes measured. There were no studies for which it was necessary to contact the authors. A kappa score was calculated for screening between the two reviewers (MPO and LM) and suggested good strength of agreement; Kappa= 0.62, 95% CI 0.53,0.71; p<0.001 (Viera 2005).
Hepatitis B Vaccine for People Living With HIV/AIDS PRISMA Study flow diagram.
Included studies
The single study we included (Castro 2009) was a single site prospective, double‐blind randomised placebo controlled trial, conducted in Spain between April 2003 to June 2006. This trial included men who have sex with men (MSM), heterosexuals, injection drug users, male and female participants (n=26). THe participants were all living with HIV and receiving ART. They were randomised into two arms with one arm receiving recombinant Hepatitis B Virus vaccine (Engerix B by SmithKline Beecham) and the other hand receiving a placebo of normal saline. At the twelfth month, ART was interrupted for six months. This study did not report on any of the outcomes of interest, but rather on viral load, genotypic mutations, different T cell subsets, and HIV‐1‐specific immune responses. A second publication from the same study (Gonzalez 2010) reported on IgG titres.
Excluded studies
We excluded 43 studies some of which were non‐randomised (Abzug 2009; Alaei 2003; Bailey 2008; Carne 1987; Horster 2010; Kalinowska‐Nowak 2007; Koblin 1999; Lao‐Araya 2011; Loke 1990; Paitoonpong 2008; Sellar 2009; Thaithumyanon 2002; Wilson 2001; Wursthorn 2011), not in PLHIV (Altuntas 2011; Mehta 2010; Mehta 2010a; Miller 1989; Odaka 1988; Pasricha 2005; Thompson 1998) testing adjuvants to hepatitis B vaccine (Cooper 2005a; Cooper 2008; Overton 2010; Overton 2011; Sasaki 2003; Sayad 2012); testing modalities of administering hepatitis B vaccine (Bunupuradah 2011; de Vries‐Sluijs 2011; Flynn 2011; Fonseca 2005; Hwang 2010; Launay 2011; McQuillan 2010) vaccines targeting other conditions (Johnson 1999; Kintu 2013; Launay 2011a). See Characteristics of excluded studies.
Risk of bias in included studies
We used the Cochrane Collaboration tool for assessing risk of bias (Higgins 2008) in this study. See: Methodological quality summary and graph (Figure 2; Figure 3). The risk of bias tables were filled independently by MPO and LM.
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Allocation
It was unclear how sequence of randomisation was generated and if there was allocation concealment.
Blinding
The study participants and personnel were blinded, it was however unclear if outcome assessors were blinded.
Incomplete outcome data
There was complete outcome data reported in the trial.
Selective reporting
All planned outcomes were reported.
Other potential sources of bias
There were no other potential sources of bias
Effects of interventions
See summary of findings Table for the main comparison
Vaccination with Hepatitis B vaccine was associated with higher IgG titres (Median 321.00; interquartile range [IQR] 970.31) compared to the control group (median 2.14; IQR 695.55), up to 12 months (p<0.05, Mann–WhitneyU‐test). At the 18 month IgG titres dropped in both the intervention (median 87.57; IQR 969.11) and control groups (median 15.28; IQR 707.70). There were no adverse events in either arm.
Discussion
Summary of main results
One RCT, published in two papers, was included in this review. (Castro 2009; Gonzalez 2010). Hepatitis B vaccine increased antibody titres to protective levels over the short term (one year). This protection was not sustained in the absence of ART. No adverse events were noted. Other outcomes such as hepatitis B infection, morbidity and mortality due to hepatitis B were not addressed.
Overall completeness and applicability of evidence
There is insufficient evidence to draw firm conclusions about the effects of hepatitis B vaccine in preventing hepatitis B infection, morbidity or mortality in PLHIV. This one trial, conducted in Spain may not be generalisable to other regions of the world with higher diseases burdens of HIV and hepatitis B. The number of participants (26) were too few and the follow‐up time was short (18 months). In addition, this trial did not cover important hepatitis B related outcomes. The participants in this trial received other vaccinations (hepatitis A, rubella, S. pneumoniae, C. tetani, C. diphtheriae) and it is unclear how they may interact with the hepatitis B vaccine. However, the declines in IgG titres following the interruption of ART would suggest that ART naive subjects would be an important subgroup to investigate, given that other studies suggest the PLHIV may respond poorly to hepatitis B vaccine, and sero‐protection may be better in ART‐experienced patients than in ART‐naive patients (Miller 2012; Siriaksorn 2006).
Quality of the evidence
Overall we grade the evidence quality as very low (Guyatt 2008). See summary of findings Table for the main comparison.
Potential biases in the review process
We minimised selection bias for in this review by using an exhaustive search strategy to identify studies, and also by including studies in all languages, unpublished and published. Titles were independently appraised and selected by two authors and differences were resolved through discussion. We searched journal electronic databases, conference databases and prospective trials registries. We contacted experts in vaccinology, hepatology and HIV whenever the need arose. We contacted authors of eligible titles to confirm that data outcomes were eligible for the review. It is unlikely that important studies were missed considering the rigorous process in study search and selection.
Agreements and disagreements with other studies or reviews
We found no other reviews on the efficacy of hepatitis B vaccine for PLHIV.
Hepatitis B Vaccine for People Living With HIV/AIDS PRISMA Study flow diagram.
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
| Hepatitis B vaccination compared to placebo for reducing morbidity and mortality in persons with HIV infection | ||||||
| Patient or population: Persons with HIV infection | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | No of Participants | Quality of the evidence | Comments | |
| Assumed risk | Corresponding risk | |||||
| Control | Hepatitis B vaccination compared to placebo | |||||
| Hepatitis B Virus infection ‐ not measured | See comment | See comment | Not estimable | ‐ | See comment | |
| Hepatitis B virus morbidity ‐ not measured | See comment | See comment | Not estimable | ‐ | See comment | |
| Hepatitis B virus related mortality ‐ not measured | See comment | See comment | Not estimable | ‐ | See comment | |
| All cause mortality ‐ not measured | See comment | See comment | Not estimable | ‐ | See comment | |
| Hepatitis B antibody titre (IgG) | The median IgG titre in the control group was | The median IgG titre in the intervention group was | Not estimable | 25 | ⊕⊝⊝⊝ | Authors report "Statistically significant (P<0.05) difference between groups using the Mann–Whitney U‐test for comparison." |
| *The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1 Randomisation and allocation concealment not described | ||||||
