Administering Influenza Vaccine to HIV patients: Does Timing Matter?

Elizabeth R. Glinka, Pharm.D., BCPS, Scott T. Johns, Pharm.D., BCPS (ID) Veterans Affairs Healthcare Systems San Diego, CA, USA

Seroprotection6 (Titer >1:40 post-vaccine)

Seroconversion6 (Pre-vaccination titer <1:10 à

>1:40) (Pre-vaccination titer >1:10 à 4 fold

increase)

Response (%)

RR (95% CI)

Response (%) RR (95% CI)

Healthy (n=89) 66 (74.2) 1 63 (70.8) 1

HIV (n=81) 34 (42)

0.56 (0.43-0.7

5) 24 (29.6)

0.42 (0.29-0.60)

Abstract (modified)

In recent flu seasons, the onset of flu did not start to dramatically increase until late November. In the U.S., influenza tends to appear in two peaks. The first occurs in late November, the second, and often larger, peak occurs between January and March1. It takes 2-4 weeks to develop peak antibody titers after influenza vaccination2. Once immunity to influenza has been acquired, it begins to wane over time. Patients who have human immunodeficiency virus (HIV) are at high risk for rapid decline in protective immunity to influenza, thus rendering them more susceptible to influenza infection3,4. It is known that antibody titers wane over time, but it is unclear if timing of influenza vaccination within the flu season affects the probability of an influenza infection later during the flu season. In the absence of randomized, prospective trials evaluating the timing of influenza vaccination in HIV patients, this retrospective analysis reviewed HIV patients and the incidence flu or influenza-like illness.

§ To evaluate if patients vaccinated early in the flu season are more likely to get influenza or ILL

§ To evaluate CD4 count at the time of vaccination and incidence of influenza or ILL

Objectives

Design §  Retrospective cohort study §  September 1, 2005 – May 31, 2013 §  Patients identified during clinic or emergency

department visits by one of the following: o  Influenza screen o  Prescription for oseltamivir, rimantidine, or amantidine

Inclusion Exclusion § HIV diagnosis § Positive influenza screen § Negative influenza screen + influenza like illness

q  Temp > 100 and q  Cough/upper

respiratory symptom

§ Negative HIV status § Another diagnosis

contributing to their symptoms

Results Conclusion

References

Acknowledgements

§ Two-thirds of our HIV patients are vaccinated prior to November 15th

§ Unvaccinated patients are more likely to get flu throughout the flu season

§  Patients who were vaccinated early compared to late were more likely to get flu later in the season

§ This study provides a clinical correlate to impaired serologic response in HIV patients

§ HIV is a risk factor for waning immunity

Patients with Influenza (N=70)

Early Flu (n=18)

Late Flu (n=52)

Age (years) – Median (Range) 49 (29-73) 48 (26-75)

Gender, male – n, (%) 18/18 (100%) 52/52 (100%)

Viral Load – n, (%) p=0.0968 §  <50 14 (78%) 27 (52%)

§  >50 4 (22%) 23 (44%)

CD4 – n, (%) §  >500 10 (56%) 31 (60%)

§  200 – 499 6 (33%) 12 (23%)

§  <200 2 (11%) 7 (14%)

Baseline Characteristics

Flu Vaccination Date

Early VD (9/1 – 11/15) Late VD (After 11/16)

Yes 30 (1.1%) 7 (0.4%)

No 2743 (98.9%) 1795 (99.5%)

Total 2773 1802

Incidence of influenza and vaccination date (p=0.0105)

Time of flu Vaccinated Unvaccinated Early (9/1 – 1/15) 11 (30%) 20 (61%)

Late (1/16 – 5/31) 26 (70%) 13 (39%)

Total 37 33

Time of flu and vaccination status (p=0.0094)

CD4 Range

Number of Patients (n=36)

Days to Event (VD to Flu) (n=36)

<200 2 (5%) <100 days 0 (0%)

>100 days 2 (100%)

200 – 499 7 (19%) <100 days 2 (29%)

>100 days 5 (71%)

>500 27 (73%) <100 days 12 (44%)

>100 days 15 (56%)

CD4 and time from vaccination to influenza (p=0.4315)

CD4 Count <100 days > 100 days

<500 2 (14%) 7 (32%)

>500 12 (86%) 15 (68%)

Total 14 22

1. CDC. Estimates of deaths associated with seasonal influenza—United States, 1976–2007. MMWR 2010;59:1057–62

2. Afluria [prescribing information]. Merck; Revised JULY2013

3. Lin, Joseph. Excess Mortality Due to Pneumonia or Influenza During Influenza Seasons Among Persons with AIDS. Arch Inter Med 2001

4. Cooper C, et al. Immunogenicity is not improved by increased antigen dose or booster dosing of seasonal influenza vaccine in a randomized trial of HIV infected adults. PLoS ONE 2011

5. Song, Joon Young. Long-term Immunogenicity of Influenza Vaccine Among Elderly. Vaccine 28 (2010) 3929-3935

6. Watcharananan, S.P.. Comparison of the Immunogenicity of a Monovalent Influenza A/H1N1 2009 Vaccine Between Health Individuals, Patients with CRF, and Immunocompromised Populations. Transplantation Proceedings, 46, 328 – 331 (2014)

7. Influenza Watch. County of San Diego Influenza Surveillance, week #15. April 12, 2014

Thank you, Scott T. Johns, for clinical guidance throughout this project, and Daniel Boggie, Pharm.D., for informatics assistance

Discussion §  Should re-vaccination be considered for patients

with HIV? §  Would high dose vaccination be warranted HIV

patients? §  What is the optimal window of time to vaccinate

HIV positive patients?

Background

Background: It is known that antibody titers wane over time, but it is unclear if the timing of influenza vaccination within the flu season affects the probability of an influenza infection later during flu season. Methods: A retrospective chart review was conducted from 9/1/2005 – 5/31/2013. Patients with laboratory confirmed influenza, influenza diagnosed by a physician, or who met criteria for an influenza like illness (ILL) were included. Results: If vaccinated early (9/1-11/15) vs. late (after 11/16) there was a higher incidence of flu, 30/2773 (1.1%) vs. 7/1802 (0.4%), p=0.0105. Vaccinated patients who developed flu were more likely to do so later in the season (after 1/16) 26/37 (70%) vs. 11/37 (30%), p=0.0094. Conclusion: HIV patients vaccinated early in the flu season were more likely to get flu or flu-like illness than those vaccinated later in the season.

Patient Identification

Early Vaccine Date (VD)

Late Vaccine Date (VD)

Patients vaccinated early (09/01 – 11/15)

Patients vaccinated late

(After 11/16)

All patients vaccinated (2005–2013)

n=2773 n=1802

Influenza or ILL 30 7

Methods

Results

Presented at ID Week, October 08 – 12, 2014, Philadelphia, PA

Presentation #1579 Elizabeth R. Glinka, Pharm.D., BCPS PGY2 Infectious Diseases Pharmacy Resident,

VA Healthcare System San Diego Elizabeth.glinka@gmail.com

(805) 815-2489