Didactic Series. Immunizations in HIV Infected Individuals. Daniel Lee, MD UC San Diego, Owen Clinic 5/11/2017

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1 Didactic Series Immunizations in HIV Infected Individuals Daniel Lee, MD UC San Diego, Owen Clinic 5/11/2017 Slides author: Ankita Kadakia, MD, AAHIVS 1

2 Learning Objectives To learn how vaccines induce immunity To learn which vaccines are recommended for all HIV positive patients and which vaccines are not recommended To understand how HIV is affected by vaccine administration To understand how immunity is affected by vaccines in HIV positive patients 2

3 How Vaccines Work 3

4 Vaccines and HIV RISK HIV can alter the efficacy and safety of giving vaccines VS HIV can affect susceptibility of the patient to diseases that vaccines normally protect against BENEFIT HIV disease progression can occur with certain vaccine administration 4

5 Efficacy of Vaccination in HIV The ability to produce antibody response is what is thought to make a vaccine efficacious Antibody levels that normally confer protection in the immunocompetent are not always well defined so difficult to extrapolate to immunocompromised Not all vaccination is effective in HIV positives but higher CD4 counts are better 5

Safety of Vaccination in HIV Activation of CD4 lymphocytes, which takes place when these cells respond to an antigenic

replication of HIV. Resting CD4 cells, although less susceptible, also are vulnerable to HIV infection.

replication is initiated These observations suggest that activation of the immune system through vaccinations could

6 Safety of Vaccination in HIV Activation of CD4 lymphocytes, which takes place when these cells respond to an antigenic stimulus, makes them more susceptible to HIV infection Activated CD4 cells, once they become infected, support replication of HIV. Resting CD4 cells, although less susceptible, also are vulnerable to HIV infection. Replication of HIV in these cells is restricted, however, until immunologic activation occurs, at which time active HIV replication is initiated These observations suggest that activation of the immune system through vaccinations could accelerate the progression of HIV disease through enhanced HIV replication and make the host more susceptible to the disease being vaccinated against 6

Study looked at immunization effect on HIV infected individuals Immune system gets activated by antigenic stimulation with vaccines, this activation

7 Study looked at immunization effect on HIV infected individuals Immune system gets activated by antigenic stimulation with vaccines, this activation also increases HIV replication 13 HIV+/10 vaccinated with Tetanus booster Measured plasma viremia before and various time points after vaccination 7

8 All 13 HIV had increased plasma viremia Higher CD4 counts has earlier peaks (~7days) in viremia and rapid return to baseline viral load Lower CD4 had later peaks (~13days) and longer return to baseline Peak viremia was associated with transient decreased absolute CD4 counts 8

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10 Poll Question #1 Which of the following vaccines would be appropriate to administer to your 21 y HIV + patient, CD4 180, VL ND on ART? A. Influenza vaccine B. Hepatitis B series C. Yellow Fever vaccine D. Zostavax 10

11 Vaccines by CD4 Count cdc.gov 11

12 Recommended Vaccines for ALL HIV + Adults PREVNAR 13 given 8 weeks prior to Pneumovax or 1 year after Pneumovax Change in 2013 from prior recommendation to vaccinate every 5 years for CD4<200 aidsinfo.nih.gov/contentfiles/reco mmended_immnizations_fs_en.p df 12

Specific IgG responses against pneumococcal serotypes 1, 6B, 14, 19F, 23F at baseline, 1 and 12 months after vaccination with Pneumovax 89 HAART-treated HIV-infected patients, 24 antiretroviral naïve

13 Specific IgG responses against pneumococcal serotypes 1, 6B, 14, 19F, 23F at baseline, 1 and 12 months after vaccination with Pneumovax 89 HAART-treated HIV-infected patients, 24 antiretroviral naïve HIVinfected and 30 non-hiv-infected healthy subjects Antibody response to Pneumovax appears to be related to CD4 cell count, with responses diminished at counts of <200 on ART in and <500 if not on ART 13

14 Hepatitis B Review of 18 studies Highly variable response rate of 18-71% in HIV-infected persons vs 60-80% in HIVuninfected persons 14

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Randomized control trial by P Cornejo-Juarez et al, CD4 counts of <200 cells/µl were associated with a response rate of 36% vs a rate of 86% in subjects with CD4 counts of >200 Study by HN Kim et al,

16 Randomized control trial by P Cornejo-Juarez et al, CD4 counts of <200 cells/µl were associated with a response rate of 36% vs a rate of 86% in subjects with CD4 counts of >200 Study by HN Kim et al, a CD4 nadir of <200 cells/µl and ongoing HIV viral replication also independently predict impaired vaccine response Study by ML Landrum et al, treatment with ART is an important determinant of vaccine : similar response rates in ART-treated individuals with CD4 counts of >350 cells/µl and <350 cells/µl. However, in individuals not on ART, CD4 counts of >350 cells/µl were associated with twice the vaccine response rate Strategies for improving antibody response to vaccination include giving a higher dose of HBV vaccine (40 µg rather than 10 µg or 20 µg). Randomized trial by MO Fonseca et al of vaccine-naive individuals with CD4 counts of >350 cells/µl, vaccination with 40 µg led to 64% seroconversion vs 40% with 20 µg (p =.008) hivinsite.ucsf.edu 16

17 Poll Question #2 21 y HIV + MSM wants to establish care with you. On exam you find genital condyloma. He is interested in HPV vaccination. What do you advise? A) No vaccination due to having genital condyloma B) Go ahead and vaccinate with HPV vaccine C)Vaccination is ok for genital condyloma but not anal condyloma 17

18 HPV for males age 9-26 aidsinfo.nih.gov/contentfiles/recommended_immnizations_fs_en.pdf 18

19 Serogroup C Similar to NY and Chicago outbreaks 19

20 Meningococcal Vaccine Menactra/Menveo: Meningoccal conjugate serogroup A, C, W, or Y For HIV age 2 and up: 2 doses 8-12 weeks apart Previously vaccinated with Menactra/Menveo needs 1 additional dose regardless of age of 1 st vaccine Booster dose every 5 years if 1 st dose age >7 20

21 Trumenba/Bexsero: Serogroup B Follow routine vaccination schedule 21

22 Poll Question #3 31 y HIV + MSM, CD4 118, VL ND, on ART for 10 years, despite adherence his CD4 has never been above 200. He plans to backpack through Africa for 3 months. He asks you for yellow fever vaccine. What do you advise? A) He needs yellow fever vaccination to travel to Africa and should get vaccinated B) Advise against vaccination because he is at risk of getting yellow fever from the vaccine and give waiver letter C) Ask him wait until his CD4 count is above 200 before vaccinating 22

23 LIVE VIRUS VACCINES need precaution. Generally avoid but if must given, CD4 >200, >14%, on ART. Use inactivated form of vaccine if available. Yellow Fever MMR Varicella Influenza nasal Oral typhoid Shingles Oral Polio aidsinfo.nih.gov/contentfiles/recommend ed_immnizations_fs_en.pdf 23

24 Shingles: To give or not to give? Theoretical risk of dissemination by LAV Zostavax contains 14 times the amount of virus as the primary varicella C Benson et al randomized trial 395 HIV +/-, 2 dose series of Zostavax vs Placebo, VZV Ab levels at 6 and 12 weeks, CD4 > 200, fully suppressed VL on ART, Ab levels doubled in vaccinated, better at higher CD4 counts, no serious AE 24

25 Abbreviations: X,; U, Use as indicated for normal hosts; R, Recommended for all in this patient category; 25 P, Precaution (per ACIP); OC, Other considerations; C, Consider; cdc.gov

26 MMR Live virus vaccine Recent outbreaks of measles in California and other countries (Germany, UK) Vaccination for CD4 > 200 Check titers first 26

27 Primary Care Guidelines for Management of HIV CID 2014:58 (1 January) e5 Poll Question #4 34 y HIV + F, CD4 101,VL ND, tells you her Indonesian partner who immigrated to the USA to live with her has been diagnosed with primary varicella. The patient does not recall having chicken pox as a child and is asymptomatic. VZV Ab is negative. What should you do? A. Vaccinate her with Varicella zoster vaccine immediately B. Do nothing unless she develops symptoms, then give Varicella zoster vaccine C. Give her VariZIG (IVIG) as soon as possible D. Give her Shingles vaccine as soon as possible 27

28 Varicella vaccination is live virus CD4 >200 Exposure treated with IVIG followed 3 months later with Varicella vaccination passive antibodies in IVIG may impair response to live-virus vaccination with MMR or varicella for up to 3 months after IVIG infusion 28

29 General Recommendations Best to vaccinate when patients are on ART and virally suppressed Benefits of vaccination outweigh risk in most cases Avoid live virus vaccines in CD4 <200, <14% Certain vaccines induce immunity better at CD4 >200 29

30 References aidsinfo.nih.gov/contentfiles/recommende d_immnizations_fs_en.pdf hivinsite.ucsf.edu CDC.gov, yellowbook, chapter 8, Immunocompromised travelers Primary Care Guidelines for Management of HIV CID 2014:58 (1 January) 30

31 Panel 7: AETC Network Map For a directory of the National and Regional AETC centers, visit:

Vaccines in Immunocompromised hosts

Vaccines in Immunocompromised hosts Carlos del Rio, MD Emory Center for AIDS Research October 2013 Immunocompromised hosts Number has increased rapidly in the past decades Broad term that encompasses different