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HIV & Aging Clinical Recommendations
Consensus is widespread for the use of most vaccines in persons living with HIV (PLWH). These recommendations are nicely summarized in an Infectious Diseases Society of America Guideline for Vaccination of the Immunocompromised Host and are also available from the Centers for Disease Control and Prevention (CDC) (Rubin 2014; CDC 2019).
There is a large body of data that vaccine-preventable illnesses occur with greater frequency and are more severe in people living with HIV (PLWH) than in age-matched control subjects. Thus, a number of vaccines are indicated in PLWH. Vaccine responsiveness can be seen even in HIV patients with advanced immunosuppression although antibody responsiveness to vaccines is better in earlier infection or after virologic suppression with antiretroviral therapy. In general inactivated vaccines are safe in HIV infection and can be administered regardless of the degree of immunosuppression. Patients with more advanced immunosuppression might need to repeat a vaccination series after immune reconstitution to obtain desired antibody response. Live vaccines are not always safe or recommended in PLWH and specific guidelines for live vaccine administration should be followed. The recommendations outlined below will focus on adults with HIV infection and will not include childhood or adolescent vaccination guidelines.
PLWH should be immunized according to the CDC schedule for adults, including regular primary and booster dose schedules based on age for Tetanus and diphtheria toxoids (Td)/Tetanus and diphtheria toxoids and acellular pertussis (Tdap), hepatitis A and B, and human papillomavirus (HPV), as well as annual influenza immunization. In addition, PLWH should receive combination pneumococcal vaccines (13-valent protein-conjugated pneumococcal vaccine (PCV13) and pneumococcal polysaccharide vaccine (PPSV23)) and meningococcal conjugate (MenACWY) vaccines regardless of age. Meningococcal serogroup B (MenB) can be administered in ages 16 to 23 if appropriate for the individual patient based on a clinical decision. Special considerations for Hepatitis B Virus (HBV) vaccination should be noted. As some HIV antiretroviral (ARV) medications have activity against HBV infection it is important to assess a patient’s HBV status prior to initiating treatment. Additionally, as new nucleoside-sparing ARV regimens are being developed, it is important to rule out an underlying HBV infection prior to removing agents with activity against Hepatitis B because of the risk of Hepatitis B flare and fulminant hepatitis. Full guidelines can be found at the US Department of Health and Human Services: Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV Infected Adults and Adolescents – Hepatitis B Virus Infection . Additional discussion of updates in vaccination
Live-attenuated organism vaccines are generally contraindicated in PLWH including the live-attenuated influenza vaccine. However, if the patient’s CD4 count is > 200/mm3 the mumps, measles and rubella (MMR) vaccine is indicated in patients not previously immunized or those without evidence of current immunity. MMR is contraindicated in patients with a CD4 count < 200/mm3 . Haemophilus influenzae type b vaccine is only recommended in PLWH who have other qualifying conditions such as asplenia . Varicella vaccine is recommended if the patient does not have documentation of previous administration or current immunity except if the CD4 count is < 200 (contraindicated). A summary of the number of doses and dose intervals for each immunization can be found in Figure 1.
The new recombinant zoster vaccine (RZV) (Shingrix) is not a live vaccine and is indicated for all people 50 years or older regardless of whether they previously received the zoster live vaccine (Zostavax) or report a history of an episode of herpes zoster. RZV needs to be stored refrigerated and reconstituted prior to administering. The only absolute contraindication is a history of an allergic or severe reaction to any component of the vaccine . Additionally, RZV should not be given during an acute episode of herpes zoster. To date there has been limited studies conducted with RZV in PLWH . In a small study conducted in 395 individuals, the RZV was found to be safe and effective. Additionally, those with a higher CD4 count had a more robust response to the vaccine . There are no additional recommendations for HIV infected patients so they should receive RZV (Shingrix) based on the same criteria as HIV uninfected patients .
In persons without HIV infection, vaccine responsiveness declines with age but differs by the vaccine. For example,hepatitis B vaccine responses begin to decline around age 35-40, whereas zoster and pneumococcal polysaccharide vaccine (PPSV23) responses begin waning about age 70-75 years (High 2010). Do vaccine responses wane at an earlier age in PLWH, and should this influence the recommended adult immunization schedule? Although data are limited, there is some suggestion that HIV does accelerate and/or enhance age-related declines in vaccine response. Two studies examined PPSV23 and pneumonia prevention in HIV-positive adults using age as a variable. Teshale et al. showed that age 45+ was associated with all-cause pneumonia, even after adjustment for vaccine status, indicating advanced age was associated with poorer vaccine efficacy (Teshale 2008). However, Rodriguez-Barradas et al. found no such association in the VACS cohort (Rodriguez-Barradas 2008). PPSV23 was protective when pneumonia was examined as an outcome in that study only in HIV-positive adults (average age 49 years). Efficacy of influenza vaccination in PLWH has been examined in several studies, with response dependent on CD4 count (Fig. 1) (Kunisaki 2009).
The most extensive examination of age and vaccine response in PLWH on ART therapy was published by Andrade et al. in a comparison of PLWH on anti-retroviral therapy (ART) <40 (mean age 31 years) vs. those > 50 (mean age 59 years) (Andrade 2010). All participants had an undetectable viral load for two years and CD4 counts >400. An HIV-negative comparison group included young (mean age 28 years) and aged (mean age 61 years) gender-matched controls. All had been immunized with tetanus toxoid (TT) during childhood, but not since; each subject was given a single TT boost. HIV-positive adults age >50 (Fig. 2) demonstrated significantly reduced humoral (serum IgG) and cellular (T cell interferon production) responses after TT immunization. Additional in vitro studies show anti-IL-10 improved responses in aged HIV-negative patients, but not in HIV-positive aged, suggesting the mechanism of vaccine non-response differs. Since TT is a recall response, and naive responses are more severely affected by age, one would anticipate naive responses would be similarly, or more severely, reduced.
A high-dose IIV is available for individuals ≥65 years of age; FDA approval was based on data showing increased immunogenicity of the high-dose vaccine in older adults. A large randomized trial over two flu seasons to examine clinical efficacy was completed. High-dose (60 µg of protein) IIV was compared to standard dose (15 µg protein) IIV for clinical efficacy and had a relative efficacy of 24% (95% CI 9.7%-36.5%) compared with standard dose IIV. There were 227 lab-confirmed cases among the 15,892 participants who got high-dose IIV, for a rate of 1.43%, and 300 cases among the 15,911 who received the standard dose IIV, for a rate of 1.83%. This exceeded the FDA-mandated definition required for superiority (lower bound of the 95% confidence interval >9.1%). No PLWH were knowingly included in this study, but HIV testing was not performed. At this time, however, the ACIP has not stated a preference for high-dose vaccine over the standard-dose vaccine in older adults.
In a small clinical trial of PLWH (n=190) randomized to receive high-dose vs standard-dose IIV, immune responses were superior in the high-dose group, similar to the results noted above for seniors (McKittrick 2013). Now, however, there is no recommendation to use high-dose IIV in HIV subjects unless they meet the age criteria, >65.
The timing of influenza vaccination in PLWH has also come into question. A retrospective cohort study (study period 2005-2013) reviewed the records of 1176 PLWH and determined that people who received the influenza vaccine “early” (September 1 through November 15) were more likely to be diagnosed with influenza or an influenza-like illness (ILI) compared to people who received the vaccination “late” (after November 15). (Glinka 2016). This study raises questions for further investigation, including the role for booster dosing during the influenza season for PLWH or offering PLWH influenza vaccination later in the fall.
As stated above, all PLWH should be vaccinated against Hepatitis B as per the CDC guidelines. In 2017, a single-antigen HBV vaccine (Heplisav-B) with a novel immunostimulatory component was approved. This vaccine is given in 2 doses 4 weeks apart and was shown to have a higher rate of seropositive hepatitis b surface antibodies when compared to 3 doses of Engerix B. This new vaccine is recommended for at risk populations including HIV infected patients. It is also to be considered when there is concern over a patient’s ability to complete the longer 3 dose series such as those experiencing homelessness . Studies of this new vaccine in HIV infected patients are limited but are expected in the future.