VACCINATING HIV+ ADULTS

Transcription

1 OLIVER KOCH VACCINATING HIV+ ADULTS BHIVA VACCINATION GUIDELINES (2015)

2 VACCINATION IN THE REAL WORLD VACCINATION - THE DEBATE CONTINUES OR OR

3 VACCINATION IS A BARBAROUS PRACTICE, AND IT IS ONE OF THE MOST FATAL OF ALL THE DELUSIONS CURRENT IN OUR TIME, NOT TO BE FOUND EVEN AMONG THE SO-CALLED SAVAGE RACES OF THE WORLD. from A GUIDE TO HEALTH by MAHATMA GANDHI

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6 VACCINATION OF HIV+ INDIVIDUALS BHIVA GUIDELINES - WHAT S NEW SINCE 2008? Use of new vaccines against human papillomavirus (HPV), shingles (herpes zoster) and pneumococcus. New recommendations for HIV positive individuals for hepatitis B, hepatitis A, meningococcus vaccinations

7 VACCINATION OF HIV+ INDIVIDUALS OVERVIEW Issues with vaccinating HIV+ individuals BHIVA Recommendations (2015) HEPATITIS B INFLUENZA PNEUMOCOCCUS HEPATITIS A HPV MENINGOCOCCUS VZV TRAVEL VACCINES

8 INTRODUCTION APPROACH TO VACCINATING HIV+ INDIVIDUALS Has the individual had all their childhood vaccinations? MMR, DPT Have they had chicken pox (or the vaccine)? Serology Are they at risk of certain infections through lifestyle? HepB, HepA, HPV, travel related Are they at increased risk from certain infection because of being HIV+? Influenza, Pneumococcus, HepB Source: Wellcome Image Library

9 VACCINATION OF HIV+ INDIVIDUALS PARTICULAR ISSUES WHEN VACCINATING HIV+ INDIVIDUALS Immune responses to vaccination are often sub-optimal in HIV-positive patients lower responses more rapid decline of titres Some (live) vaccines contraindicated

10 VACCINATION OF HIV+ INDIVIDUALS GENERAL PRINCIPLES Most data on vaccinations in HIV-infected individuals have not examined efficacy directly, but rather immunogenicity Protective antibodies often correlated with CD4 cell count. Inactivated vaccines are generally safe in HIV infected individuals. Certain live vaccines have sufficient safety data and are thus recommended in HIV-infected patients who have CD4 cell counts 200 cells/microl.

11 HEPATITIS B

12 HEPATITIS B HBV IN HIV-POSITIVE ADULTS in HIV+ higher risk of HBV infection higher risk of HBV chronicity Co-infected persons show increased rates of progression to cirrhosis and liver cancer and a higher mortality than persons with either infection alone. Artistic impression of hepatitis B viruses near human lymphocytes. Image copyright: Alexander Suh & somersault18:24. doi: /ncomms2798

13 HEPATITIS B HBV VACCINATION IN HIV-POSITIVE ADULTS After standard vaccination, rates of HBsAb seroconversion (>10 IU/L) range between 7% and 88%, and correlate strongly with CD4 cell counts and viral load.

14 HEPATITIS B HBV VACCINATION IN HIV-POSITIVE ADULTS systematic review and meta-analysis of five studies including a total of 883 patients compared HBsAb response with high-dose (40 μg) vs. standard-dose (20 or 10 μg depending on vaccine type) vaccination: High-dose vaccination increased response rates with a pooled OR of 1.96 (95% CI ) [Ni et al. 2013] 1 + 4: Engerix 20μg vs. 40μg 2: Recombivax 10μg vs. 40μg 5: GenHevac 20μg vs. 40μg 3: Previous failure to respond

15 HEPATITIS B HBV VACCINATION IN HIV-POSITIVE ADULTS Potsch et al. (2010): HBAbs response rates were 83% and 91% after three and four double-doses, respectively, and HBsAb levels were higher with the four-dose schedule (note: mean CD4 402cells/ml in this study).

16 HEPATITIS B BHIVA RECOMMENDATIONS - PRIMARY VACCINATION Engerix B should be given as a double-dose (total 40 μg); with HBvaxPRO the 40 μg formulation should be used; when using the adjuvanted vaccine Fendrix the standard 20 μg formulation should be given regardless of vaccine type, four vaccine doses are given at 0, 1, 2, and 6 months ultra-rapid vaccination course considered only in selected patients with CD4 cell counts >500 cells/μl where there is an imperative need to ensure rapid completion of vaccination and/or where compliance with a full course is doubtful following completion of the primary vaccine course, HBsAb levels should be measured 4 8 weeks after the last vaccine dose

17 HEPATITIS B BHIVA RECOMMENDATIONS - NON RESPONDERS Anti-HBs levels are measured 4 8 wks after the last dose: <10 IU/L: 3 further high doses (40 μg) at monthly intervals (or standard dose of Fendrix) 10 but <100 IU/L: one further (40 μg) dose depending on the level of risk, revaccination of nonresponders may be delayed until the viral load is suppressed on ART and the CD4 cell count has increased >350 cells/μl

18 HEPATITIS B BHIVA RECOMMENDATIONS Monitoring of HBsAb levels depends on initial response and CD4 count at vaccination yearly if IU/L; every 2 yrs if >100 IU/L If HBsAb levels drop to <10 IU/l, offer booster dose (40μg)

19 HEPATITIS B HBV VACCINATION DECISION FLOW-CHART HBV#vaccination#decision#flowAchart#

20 ISOLATED HB CORE AB+ ISOLATED HEPATITIS B CORE ANTIBODY IN HIV-INFECTED PATIENTS Usually signifies infection with HBV in the past with subsequent loss of anti-hbs. It occurs in 6.6% to 58.6% of HIV-infected patients The clinical significance of isolated anti-hbc is unknown but it may indicate chronic or, more likely, resolved infection in HIV-infected individuals. In a low-prevalence country, isolated anti-hbc may also represent a false-positive result. Incidence of HBV viraemia in HIV-infected patients with the isolated anti-hbc pattern ranges from 1% to 36%.

21 INFLUENZA

22 INFLUENZA INFLUENZA VACCINE two types of influenza vaccines available in the UK: inactivated live-attenuated vaccines (safety data in HIV lacking) Inactivated vaccines are usually multivalent: Trivalent inactivated vaccines (TIVs) typically contain two influenza A strains and one influenza B strain. Quadrivalent preparations contain one additional influenza B virus

23 INFLUENZA INFLUENZA IN HIV-POSITIVE ADULTS Increased severity and greater risk of complications, resulting in excess hospitalisation and mortality (Safrin et al. 1990; Fine et al. 2001; Lin et al. 2001) ART reduces the rates of hospitalisations and mortality, although the risk of severe outcomes remains comparable to that of other high-risk groups for which annual influenza vaccination is recommended Antibody responses to vaccination correlated with CD4+

24 INFLUENZA RECOMMENDATIONS All HIV-positive adults should be offered annual influenza vaccination (parenteral non-replicating vaccine) Ideally give between September and early November Quadrivalent vaccine may be preferred where available Single vaccine dose recommended Close contacts of HIV-positive persons should be offered annual influenza vaccination

25 INFLUENZA DISCUSSION / CONSIDERATIONS Cost efficacy of quadrivalent vaccine? Who should vaccinate? GP? HIV Clinic? Patient may not attend HIV clinic for 6 months or more GP may not stock quadrivalent vaccine Who should pay for vaccination? Primary care / secondary care budget? Who will vaccinate contacts?

26 PNEUMOCOCCUS

27 PNEUMOCOCCUS THE PNEUMOCOCCAL VACCINE There are two types of pneumococcal vaccine: Pneumococcal polysaccharide vaccine (PPV) contains purified capsular polysaccharide from each of 23 capsular types of pneumococcus (PPV23) Pneumococcal conjugate vaccine (PCV) contains polysaccharide from thirteen common capsular types (PCV13). These are conjugated to protein (CRM197) using similar manufacturing technology to that used for Haemophilus influenzae type b (Hib) and meningococcal conjugate vaccines.

28 PNEUMOCOCCUS PNEUMOCOCCAL POLYSACCHARIDE VACCINE (PPV) Most healthy adults develop a good antibody response to a single dose of PPV by the third week following immunisation. Antibody response may be reduced in those with immunological impairment and those with an absent or dysfunctional spleen. Children younger than two years of age show poor antibody responses to immunisation with PPV.

29 PNEUMOCOCCUS PPV-23 IN HIV+ Only one clinical trial of PPV-23 in HIV+ (French et al. 2000) 1312 HIV-infected Ugandan adults no clinical efficacy of vaccine Limitations: The overall low number of cases of invasive pneumococcal disease The absence of antiretroviral therapy (ART), which probably contributed to the high rates of overall mortality seen in this trial (53%) Suboptimal vaccine immunogenicity since approximately 45 percent of the patients had advanced immunosuppression (eg, CD4 cell count <200 cells/mm3) systematic review of multiple observational studies suggests a benefit of polysaccharide vaccine (Pedersen et al. 2011)

30 PNEUMOCOCCUS PNEUMOCOCCAL CONJUGATE VACCINE (PCV) The antibody response in young children can be improved by conjugating the polysaccharide to proteins such as CRM197. The conjugated vaccine is known to be immunogenic in children from two months of age.

31 PNEUMOCOCCUS PCV IN HIV+ Clinical trials have demonstrated significant efficacy and immunogenicity of the 7-valent conjugate vaccine among HIV-infected adults. Studies have only evaluated immunogenicity (not clinical efficacy) of the 13-valent conjugate vaccine (PCV13) among HIV-infected adults.

32 PNEUMOCOCCUS PCV+PPV - PRIME-BOOST Some evidence that serological responses to PCV serotypes are increased by boosting with either PCV or PPV But no studies to support the effectiveness of this approach to prevent disease end-points ACIP recommendations for PCV13 and PPSV23 use in adults with immunocompromising conditions (incl. HIV): dose of PCV13 first, followed by a dose of PPSV23 at least 8 weeks later BHIVA: PCV13; PPSV23 only if fits national programme criteria

33 HEPATITIS A

34 HEPATITIS A HEPATITIS A Spread mostly by faeco-oral route Infection may be spread during sexual contact in MSM Hep A in HIV: not worse in HIV-positive patients

35 HEPATITIS A PERSONS AT RISK / INDICATION FOR VACCINATION Household and sexual contacts of infected persons Travellers to countries where HAV is common Men who have sex with men Injecting and non-injecting drug users Individuals at risk of infection during outbreaks Those with occupational exposure to HAV (e.g. laboratory workers, sewage workers) Persons with haemophilia Persons with special needs living in residential institutions, and their carers

36 HEPATITIS A HAV VACCINATION IN HIV+ Less than half of vaccine recipients experience seroconversion after a single vaccine dose; responses increase to over 70% after two doses (compared to 100% in HIV neg) Further increasing the number of vaccine doses improves antibody levels and the longevity of response but does not significantly improve overall seroconversion rates.

37 HEPATITIS A RECOMMENDATIONS In at risk HIV+ population offer monovalent HAV vaccine Note: HAVRIX contains 1440 ELISA units of Hepatitis A virus (inactivated) and TWINRIX only 720 ELISA units. Patients with CD4 cell counts >350 cells/μl should be offered two vaccine doses at 0 and 6 months (standard course). Patients with CD4 cell counts <350 cells/μl should receive three vaccine doses at 0, 1, and 6 months in order to increase antibody levels and longevity, especially if they are likely to be at continued risk of exposure. Patients at continued risk of exposure receive a boosting vaccine dose every 10 years (non-hiv: 25 years).

38 MENINGOCOCCUS

39 MENINGOCOCCUS BHIVA RECOMMENDATIONS Indication for vaccination as per national programme (ie HIV alone not an indication) Difference to standard recommendations: HIV+ adults should be offered two vaccine doses at the interval of 2 months in order to increase immunogenicity [1C] If at ongoing risk MenACWY booster every 5 years [2C]

40 VARICELLA ZOSTER VIRUS

41 VARICELLA ZOSTER VIRUS VARICELLA ZOSTER VIRUS - CHICKEN POX HIV-positive adults with a negative or uncertain history of chickenpox or shingles should undergo VZV IgG testing to determine susceptibility to primary infection and reactivation. VZV IgG seronegative patients who have a CD4 cell count >200 cells/μl and preferably are established on ART should be offered two doses of the chickenpox vaccine 3 months apart.

42 VARICELLA ZOSTER VIRUS VARICELLA ZOSTER VIRUS - SHINGLES Zostavax: high dose live attenuated VZV vaccine, 14 times more potent than the varicella vaccine Licensed for immune competent adults aged 50 yrs Boosts natural immunity, reduces incidence of herpes zoster by at least half and frequency of post-herpetic neuralgia by ~ two thirds - Protection expected to last for 5 years VZV IgG seropositive patients who have a CD4 cell count >200/ μl and preferably are established on ART should be offered one dose of the shingles vaccine in line with national age- related indications (currently adults aged 70 and 78/79)

43 HUMAN PAPILLOMA VIRUS

44 HPV GENERAL INDICATIONS Since 2008, HPV vaccination is routinely recommended for all girls aged 12 13, along with a catch up programme for girls 13 to under 18 years of age. Two vaccine doses are given to those aged 9 14 years, and three doses to those aged years. In Scotland Gardasil (4vHPV) used since 2012 (in preference to Cervarix (2vHPV)) which in addition to providing protection against HPV types 16 and 18 also provides protection against HPV types 6 and 11 responsible for the majority of cases of genital warts in the UK.

45 HPV HPV IN HIV+ increased risk and rate of HPV acquisition and persistence frequent carriage of multiple HPV types increased risk of HPV-related disease including rapidly progressive malignancies 600, , , , , ,000 Annual number of cancer cases worldwide HPV-associated cases Total cases Genital warts more common, often resistant to treatment Cervix Anus Vagina Penis Cathay et al. AIDS Rev 2014 Pharynx Higher risk of cervical cancer (~4 fold) Adler DH. Curr HIV Res 2010; 2. Chen et al. AIDS 2014; 3. Denslow et al. Int J STD AIDS 2014;

46 HPV HPV RELATED ANAL CANCER IN HIV+ Higher risk of anal cancer (MSM > Other men = Women) [Silverberg et al. Clin Infec Dis 2012]

47 HPV HPV VACCINE IN HIV-POSITIVE ADULTS Studies that have most commonly employed 4vHPV, vaccination has been shown to be safe and immunogenic in HIV+. Overall seroconversion rates are high in all groups, and both seroconversion rates and antibody titres are higher than with natural infection, and highest in those receiving ART and showing high CD4 cell counts and a suppressed viral load.

48 HPV JCVI HPV SUB-COMMITTEE MEETING 8TH JUNE 2015 At the list price of the vaccine, vaccinating HIV +ve MSM up to the age of 45 was cost effective. Using the threshold price (combined vaccine and administrative costs) vaccinating all MSM up to 45 was also within the cost-effectiveness. Warts prevention was still a main influencing factor for the targeted programme being cost effective.

49 TEXT BHIVA RECOMMENDATIONS 2015 Previously unvaccinated HIV-positive men and women aged up to 26 years should be offered HPV vaccination, regardless of CD4 cell count, ART use, and viral load. - cost effectiveness? Previously unvaccinated HIV-positive MSM aged up to 40 years should be offered HPV vaccination, regardless of CD4 cell count, ART use, and viral load suggestion: Previously unvaccinated HIV-positive women aged up to 40 years to be offered HPV vaccination, regardless of CD4 cell count, ART use, and viral load - cost effectiveness / evidence? Three doses of the quadrivalent 4vHPV vaccine should be administered at 0, 1 2, and 6 months. In ART-naïve patients with CD4 cell counts <200 cells/μl vaccination may be deferred until the patient is established on ART. Use 9vHPV in both men and women once it becomes available - Cost effectiveness?

50 TRAVEL VACCINES

51 HIV & TRAVEL CONSEQUENCES OF BEING NORMAL normal life expectancy freedom from an early death freedom to enjoy the world assumption that this means no restrictions or special measures Reference: BMJ 2011; 343:d6016 doi: /bmj.d6016

52 HIV & TRAVEL HIV+ TRAVELLERS Danish study: During the previous two years 49% had travelled outside Europe Pre-travel advice was sought by only 38%, and travel insurance was taken out by 86% However, 29% / 74% did not inform the advisor/the insurance company about their HIV status Ref: Nielsen, U. S., Jensen-Fangel, S., Pedersen, G., Lohse, N., Pedersen, C., Kronborg, G., et al. (2014). Travelling with HIV: a cross sectional analysis of Danish HIV-infected patients. Travel Medicine and Infectious Disease, 12(1),

53 TEXT TRAVEL VACCINES IN HIV+ BHIVA commonly recommends measuring antibody response to vaccines, e.g. rabies, yellow fever Feasibility for travel clinics? Cost? Traveller vs NHS? Travel medicine not covered by NHS

54 TRAVEL MEDICINE TRAVEL CLINIC AT RIDU TravelClinic/Pages/default.aspx

55 DISCUSSION POINTS

56 DISCUSSION DISCUSSION POINTS Issues surrounding vaccination highlight importance of communication between HIV services and GPs (whenever possible) - dosing regimen, live vaccines, etc. Who is responsible for vaccinations and follow up (antibody response)? GP vs HIV service? Out of which budget should vaccinations be paid for? BHIVA guidelines - a wish list? Achievable? Cost efficacy? Clinical efficacy?

57 QUESTIONS? Photo: O.Koch