Prevention Of Opportunistic Infections
Prevention of opportunistic infections in HIV+ patients is important in reducing morbidity and mortality for these patients. Hepatitis A and Hepatitis B are two important infections in HIV+ patients for which the main method of prevention is vaccination. The aim of this audit was to evaluate the compliance of Beaumont Hospital’s Infectious Diseases department with the European AIDS Clinical Society (EACS) guidelines with regards to Hepatitis A and Hepatitis B vaccinations in patients attending the HIV clinic. HIV patients have a suboptimal response to vaccination due to the immunodeficiency caused by the destruction of CD4+ cells. Regardless, EACS guidelines suggest that HIV+ patients should be vaccinated against Hepatitis B. EACS guidelines also suggest that HIV patients should get vaccinated against Hepatitis A if other risk factors are present (eg. IVDU). 100 HIV+ were randomly selected for evaluation of documentation of vaccination and immunity status. It was found that compliance with vaccination guidelines for Hepatitis B was excellent (93.2%). However, compliance to vaccination guidelines for Hepatitis A was significantly poorer (44.4%). The reason for this might be the relative significance on morbidity and mortality, with Hepatitis B being far more significant. The audit also reviewed vaccination practices against other opportunistic infections such as Streptococcus pneumoniae, influenza and Human Papilloma virus infections, with compliance to vaccination guidelines being excellent for the first two. Compliance to HPV vaccination guidelines is poor as this vaccine is not currently being offered in Beaumont hospital.
Human Immunodeficiency Virus (HIV) infection is a chronic illness that causes a weakened immune system, allowing patients to become susceptible to a wide range of opportunistic infections (1). HIV affects both arms of the immune system: the innate immunity and the adaptive immunity(2). The virus causes dysregulation of the innate immune system by affecting the main effector cells in this system, the natural killer cells (NK) and plasmacytoid dendritic cells (pDC) (2). The way it which HIV affects NK cells is not fully understood, however it could be caused by the effect the virus has on the cytolytic activity and the cytokine production of NK cells, making HIV infected cells resistant to NK cell-mediated killing (2). Alternatively, the virus induces apoptosis of pDCs through interfering with the cell cycle. Additionally, HIV causes dysregulation to the adaptive immune system by inducing cellular depletion and functional abnormalities in CD4+ T-Lymphocytes, which secrete cytokines and play an important role in activating the cells of the innate immune system, cytotoxic T cells, B-lymphocytes, as well as nonimmune cells (2)(3). The virus also causes the deletion of CD8+ T-Lymphocytes, which form a part of the adaptive immune response(2). CD4 cells can be measured in the blood and, along with viral load, are used to monitor the progression of the infection (4). Due to the weakened immune system, opportunistic infections often occur more severely in HIV+ patients when compared to the general population (4)(5). As a result of the virus’ effects on the immune system, HIV+ patients are vulnerable to a spectrum of diseases, with liver disease being the 3rd most common cause of death (4). Hepatitis A Virus (HAV) and Hepatitis B Virus (HBV) are associated with great morbidity and mortality in HIV+ patients (4). Prevention of Hepatitis A (HAV) and B Viruses (HBV) infections is achieved mainly through vaccination (6). People at risk of HIV are also at risk of HBV infection as the two viruses have similar routes of transmission (4). If HBV infection becomes chronic, the patient is at risk of several complications, including liver cirrhosis and hepatocellular carcinoma (4). Alternatively, the main route of transmission of HAV is the faecal-oral route (4). HAV does not give rise to a chronic state but can produce a prolonged vireamia, which poses a public health challenge as it might lead to transmission within a community (4). Due to the impaired immune system of HIV+ patients, the response to vaccination can be suboptimal (7). According to current European AIDS Clinical Society (EACS) guidelines, all HIV+ patients should be vaccinated against HBV (4). The vaccine for HBV is a recombinant vaccine consisting of 95% Hepatitis B surface antigen (HBsAg) and 5% yeast derived proteins (4). The vaccine is given in a 3-dose course, with the 1st dose being given at time “0”, 2nd dose 1 month after time 0 and the third dose 6 months from time 0 (4). The HAV vaccine, however, is only given if there are other risk factors present in the patient, such as intravenous drug use (IVDU), men who have sex with men (MSM), liver disease or if they originate from or reside in an area with high prevalence of HAV infection (4)(8). The vaccine recommended for HIV+ patients is a formaldehyde inactivated vaccine, which is given as a 2-dose course at least 6 months apart (4). This Audit reviewed the Beaumont hospital HIV patient cohort and evaluated the compliance of the hospital with the aforementioned guidelines.
Materials and Methods
A retrospective audit was performed involving the Beaumont hospital HIV patient cohort, which is comprised of 809 current and past patients who have attended the Infectious Diseases HIV clinic for treatment. Guidelines for management of vaccination in this cohort come from the European AIDS Clinical Society (EACS). Dose of Hep B vaccine given to patients was 20 μg at vaccination and 40 μg at re vaccination (in cases where revaccination was indicated). The purpose of this audit was to review Beaumont Hospital’s Infectious Diseases department clinical practice with regards to vaccination in this cohort against the EACS guidelines for Hepatitis A and Hepatitis B. 100 patients were randomly selected from the 809 patient cohort using an online random number generator. Patients were included if they were adults with a confirmed HIV diagnosis and had attended the Beaumont HIV outpatient clinic at least once. Some patients were excluded from this audit for a number of reasons including death, inability to locate chart, referral to different hospital or deportation from Ireland. All attempts to locate a patient’s chart, regardless of whether they were a current attender of the HIV clinic or not, were made before discluding them from the audit. This included reviewing charts on wards or retrieving charts from offsite. Each patient was assigned an audit number which was kept in a document in the ID department in Beaumont hospital. Medical charts of the selected patients were then reviewed for documentation of vaccination status and for other information relevant to the audit questions. Other relevant information captured included each patient’s sex, age, year of diagnosis, CD4 count at the time of vaccination, CD4 nadir, HIV viral load at time of vaccination, Hepatitis B immunity, and Hepatitis A immunity, and whether or not the patient was receiving Highly Active Antiretroviral Therapy (HAART) at the time of vaccination. These data points have been captured in Table 1. HIV positive patients should also be vaccinated against Streptococcus pneumoniae (Prevnar or Pneumovax), influenza, and a select group of these patients should be vaccinated for human papilloma virus (HPV). Additional data regarding these vaccinations were recorded for each patient. No identifying information was recorded for this audit.
100 HIV+ patients who have attended Beaumont Infectious Diseases services were evaluated for compliance with the EACS guidelines on HAV and HBV vaccination. The mean age of selected patients was 42.7 years. 55 patients (55%) were males and 45 patients (45%) were females. It was found that Hep B vaccination was indicated in 59 of 100 patients, of which 55 received the vaccination (93.2%) and 4 did not (6.8%) even though they met the criteria for vaccination. There was no documentation as to why these patients were not vaccinated. With the additional vaccination that occurred because of the HIV clinic, 95 patients (95%), overall, are considered immune to the Hepatitis B virus. The breakdown on how immunity occurred is as follows: 55 patients (55%) were vaccinated in Beaumont hospital ID services; 16 patients (16%) did not need the vaccination as they had adequate antibodies, although ethology of immunity was not documented; 15 patients (15%) did not require vaccination due to a previous resolved HBV infection; 7 patients (7%) were chronically infected with Hepatitis B virus and 2 patients (2%) were vaccinated elsewhere including being vaccinated abroad or in a different healthcare facility in Ireland (see figure 1). However, 5 patients (5%) were considered non immune, with 4 patients (4%) not being vaccinated and 1 patient (1%) missing the vaccination appointments. Of the 55 patients vaccinated with the Hep B vaccine, 35 patients (63.6%) responded to the vaccination and developed protective antibodies against Hepatitis B virus surface antigen (Anti HBs titre > 10 mIU/mL) and 20 patients (36.4%) did not respond to the vaccine (Anti HBs titre < 10 mIU/mL) (see figure 2). 37 patients had inadequate antibody titre (Anti HBs titre < 10 mIU/mL) and needed re vaccination, of these only 20 patients (54.1%) were re-vaccinated with the Hep B vaccine. Alternatively, Hepatitis A vaccination was indicated in 9 patients; with only 4 patients being vaccinated at the time of the audit (44.4%). None of the patients received re-vaccination for Hepatitis A. Most patients (86%) had at least one risk factor for Hepatitis A. The most common risk factor for development of Hepatitis A among these patients was originating from or residing in areas where there is high prevalence of Hep A infection (64% of patients). Many of these patients were from the African continent (89.01%). This audit also looked at the compliance of the hospital with the guidelines with regards to Streptococcus pneumoniae, flu and HPV vaccinations (see figure 3). Pneumovax vaccine was given to 97 patients (97%). 3 patients (3%) did not receive the vaccine. The yearly influenza vaccine had been received in 92 patients (92%). 8 patients did not get the flu vaccine. The HPV vaccine was not documented in any of the patients (0%), as it is currently not being offered by the hospital and they had not sought it elsewhere.
Figure 1. Immunity in HIV+ patients against Hep B virus.
Figure 2. Response to Hep B vaccination.
Figure 3. Delivery of Flu, pneumovax, prevnar and HPV vaccinations.
Table 1. Data collection pro forma for the audit.
Overall, Beaumont Hospital’s Infectious Diseases department clinical practice was excellent when it came to Hepatitis B vaccination, as 93.2% of patients were vaccinated against Hep B where vaccination was indicated. However, only 54.1% of non responders were re-vaccinated against Hepatitis B, Which could be improved by putting more emphasis on checking anti-HBs titres on follow up clinic reviews and offering re-vaccination where it is indicated. The choice of timing for vaccination is important, as research has suggested that patients with a suppressed viral load have a longer duration of response and a higher antibody titre to the virus (4). Additionally, it is the responsibility of the doctor to make sure that guidelines are followed due to the best interest of the patient. Therefore, an introductory teaching session should be offered to all new doctors starting in the Infectious diseases department to educate them about these and other guidelines. The use of a template to document anti-HBs titre on follow up sessions could help in reminding doctors of the patient’s status and the subsequent need for re-vaccination in non-responders. Alternatively, Compliance with Hep A vaccination guidelines was significantly poorer, with 44.4% of patients receiving vaccination where vaccination was indicated (HIV+, another risk factor for Hepatitis A and negative anti-Hep A IgG antibodies). This may be due to Hep A infection being less dangerous and less severe than Hep B infection. The risk of liver cirrhosis and hepatocellular carcinoma is higher in HIV+ patients if they acquire HBV co-infection compared to patients who have HBV infection alone (9). Whereas, the acquisition of Hepatitis A virus by HIV+ patients is associated with prolonged Hepatitis A viraemia, which may lead to an outbreak in the community (10). However, on discussion with the NCHDs attending the clinic, this, too, was likely a result of not being aware of the EACS guidelines. Evaluating risk factors for Hep A infection when a patient first comes to clinic could lead to better compliance with the guidelines. An introductory session which would also include information about Hepatitis A risks would also improve vaccination for these patients. In total, 9 HIV+ patients required Hepatitis A vaccination. The two most common risk for Hepatitis A in this population was men who have sex with men (MSM) and originating from an endemic area, with the two being present in 5 patients out the 9 patients (see figure 4). There was excellent compliance with the guidelines for Streptococcus pneumoniae as 97% of patients were vaccinated with Pneumovax. However, 0% were vaccinated with prevnar. The benefit of Prevnar (PCV-13) is that it is a once-off vaccine, in contrast to Pneumovax (PCV-23) which needs to be re-administered every 5 years (11). Although Prevnar would be preferred, it is not stocked in the hospital’s Infectious Diseases department pharmacy due to issues with allocation of resources. Additionally, compliance to the Influenza vaccine guidelines was excellent, with 92% of patients being vaccinated in the last flu season (2017/2018). 0% of patients received the Human Papilloma Virus vaccine (HPV), as the vaccine is not currently being offered in Beaumont Hospital due to a combination of resource allocation and specifically because there is not enough staffing to provide additional vaccinations at present. However, the department is trying to source an additional nurse specialist to resolve this issue.
Figure 4. Hepatitis A infection Risk factors in the patients where vaccination was indicated.
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