Immunisation in people living with HIV. Dr Bernadett Gosnell, Department of Infectious Diseases, UKZN

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1 Immunisation in people living with HIV Dr Bernadett Gosnell, Department of Infectious Diseases, UKZN

2 Calculating immunisation s return on investment In Gavi-supported countries, x (full income approach) 3x 7x 9x 18x (cost of illness) Public infrastructure Pre-school education Community health workers Immunisation

3 Why vaccinate? Individual: preserve health and avert adverse outcome Societal benefit:

4 Why vaccinate HIV population Have impaired host defenses Increased risk of vaccine preventable diseases Prevent severe forms of disease Shared transmission routes (HIV) For specific risk behaviours or comorbidities

5 Sipho K. Dlamini Shabir A. Madhi Rudzani Muloiwa Anne von Gottberg Mahomed-Yunus S. Moosa Susan T. Meiring Charles S. Wiysonge Eric Hefer Muhangwi B. Mulaudzi James Nuttall Michelle Moorhouse Benjamin M. Kagina S Afr J HIV Med. 2018;19(1), a839.

6 Guideline development Full day workshop Presentation of local data Discussion Recommendation Consensus if no local data Draft of guidelines Evidence based Based on best international practice Circulated and comments received Review of guideline recommendation Every 3-5 years Identify gaps in local data help inform future guidelines

7 1= Very fit 2= Well Clinical frailty scale HIV and AIDS 3= Well, with treated chronic disease 4= Apparently vulnerable 5= Mildly frail 6= Moderately frail 7= Severely frail 8= Very severely frail 9= Terminally ill Canadian Study on Health & Aging, Revised 2008.

8 What vaccines? Influenza Pneumoccocal disease Pertussis Diphtheria and tetanus Hepatitis A Hepatitis B Human papilloma virus Poliovirus Measles, mumps and rubella Varicella Zoster

9 Influenza deaths Seasonal influenza all-cause mortality rates were 23.0 (95% CI ) per population annually (2.3% [95%CI 2.3% 2.4%] of all deaths) More than 45% of seasonal influenza- and RSVassociated deaths occur out-of-hospital in South Africa. These data suggest that hospital-based studies may substantially underestimate mortality burden. Cohen, C., Walaza, S., Treurnicht, F. K., McMorrow, M., Madhi, S. A., McAnerney, J. M., & Tempia, S. (2018). In- and Out-of-hospital Mortality Associated with Seasonal and Pandemic Influenza and Respiratory Syncytial Virus in South Africa, Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America, 66(1),

10 Case-fatality proportion Influenza case-fatality SA Cohen C, et al. (2015) Mortality amongst Patients with Influenza-Associated Severe Acute Respiratory Illness, South Africa, PLoS ONE 10(3) HIV No HIV Age-groups (years) Case-fatality proportions by age group and HIV status amongst patients hospitalized with influenza-associated SARI at four sentinel surveillance sites in South Africa, (n = 1039).

11 Influenza Key Points: Influenza causes substantial mortality in South Africa. The peak burden of mortality experienced in children <1 year age and HIV-infected adults aged years. HIV infected individuals experienced a around 10 fold higher estimated rate of death in all age groups Other risk factors for death were the presence of non-hiv underlying illness and co-infection with S.pneumoniae.

12 Influenza 1 dose yearly (March-May) Irrespective of CD4+ cell count, HIV viral load or pregnancy status Cost R42.05 (government sector) S Afr J HIV Med 2018; 19(1)

13 Invasive pneumococcal disease HIV infected individuals have a 35 to 60 fold increase of invasive IPD Higher rates of bacteraemia Often at risk of recurrent pneumococcal infections Associated with a 2-fold higher mortality rate Risk elevated despite the use of ART Some good reasons why vaccination important in this population 3 main concerns previously Lack of consensus on protective levels Optimal timing of immunization Durability of response and protection Vaccines available Polysaccharide vaccine (PPV23) Conjugate vaccine (PCV13) Cohen C, Naidoo N, Meiring S, de Gouveia L, von Mollendorf C, Walaza S, et al. (2015) Streptococcus pneumoniae Serotypes and Mortality in Adults and Adolescents in South Africa: Analysis of National Surveillance Data, PLoS ONE 10(10):

14 Pneumococcal vaccination: what have we learnt so far and what can we expect in the future? A. Torres, P. Bonanni, W. Hryniewicz, M. Moutschen, R. R. Reinert, T. Welte, Eur J Clin Microbiol Infect Dis. 2015; 34(1): Correction in: Eur J Clin Microbiol Infect Dis. 2015; 34(2):

15 French cohort study

16 Conclusion: Despite a stable prevalence of HIV and the increased roll-out of HAART, the burden of IPD has not decreased among HIV-infected adults in South Africa. ongoing need to monitor diseases and HAART program effectiveness to reduce opportunistic infections in African adults with HIV/AIDS, consider alternate strategies including pneumococcal conjugate vaccine immunisation for the prevention of IPD in HIV-infected adults. PLoS ONE 6(11):e27929

17 Age-specific incidence rates for Lab-confirmed IPD: GERMS-SA, South Africa, GERMS-SA ANNUAL SURVEILLANCE REPORT FOR LABORATORYCONFIRMED INVASIVE MENINGOCOCCAL, HAEMOPHILUS INFLUENZAE AND PNEUMOCOCCAL DISEASE, SOUTH AFRICA, 2017 Susan Meiring1, Cheryl Cohen2, Linda de Gouveia2, Mignon du Plessis2, Jackie Kleynhans2, Vanessa Quan1, Sarona Lengana2, Sibongile Walaza2, Anne von Gottberg2

18 Immune response to polysaccharide vaccine Eur J Clin Microbiol Infect Dis (2015) 34:19-31

19 Immune response to conjugate vaccines

20 Immunogenicity: Opsonophagocytic Activity Following One and Two Doses of PCV13 and PPV23: Serotype 1 Paradiso PR. Clin Infect Dis 2012; 55:

21 Study design: HIV infected individuals vaccinated with either PCV13 followed by PPSV23 four weeks later or twice PPSV23 four weeks apart (total no analysed= 52) Our study suggests that combining PCV13 with PPSV23 elicits a greater magnitude of IgG and OPA immune response compared to PPSV23 alone in HIV-infected individuals with CD4 count >200 cells/mm3 over the study period This Study adds to evidence supporting current pneumococcal vaccination recommendations combining the conjugate and polysaccharide pneumococcal vaccines in the United States and Europe for HIV-infected individuals. Sci. Rep. (2016) 6:32076

22 Pneumococcal All HIV-infected regardless of CD4+ with suppressed viral load Prime-boost approach PCV13 followed by PPV23 eight weeks later PCV13 alone is sufficient Cost: PCV13 R PPV23 R S Afr J HIV Med 2018; 19(1)

23 Hepatitis B Notifiable disease (category 2 -same as tuberculosis) Co-infection with HBV and HIV is considered endemic in sub-saharan Africa, including South Africa. In HIV-infected patients receiving long-term HAART, HBV status did not influence HIV suppression or CD4 increase. However, mortality was highest among those with CH-B and was mostly due to liver disease despite HBV-active HAART (Hoffmann, Christopher J et al. Hepatitis B and Long- Term HIV Outcomes in Co-Infected HAART Recipients. AIDS (London, England) (2009): ) Infant Hep B vaccine in SA from 1995

24 Hepatitis B Prevalence in HIV+ ranges 0.4%- 23% Administration of vaccine shown to be safe Recommended: double dose (40 μg) at month 0, 1, 2, 6 (WHO recommends single dose vaccine at month 0, 1, 6) Cost per dose R26.76 Best responses if undetectable VL & CD4+ >200 cells/µl S Afr J HIV Med 2018; 19(1)

25 Diphtheria Outbreaks in South Africa 15 cases occurred in ethekwini, KZN province 2015 most cases occurred in people who were not vaccinated or partially vaccinated 2 confirmed cases KZN Diphtheria kills 1, infects 3 in Western Cape August lab-confirmed cases & 1 asymptomatic carrier 3 cases (aged 20,11 & 10 yrs), KZN province since March of the cases have died Catch-up campaign

26 Tetanus-diphtheria (Td) Vaccinated irrespective of CD4+ count Booster vaccine every 10 years (until more data available) Cost R (awaiting confirmation) S Afr J HIV Med 2018; 19(1)

27 Human papilloma virus In SA HPV- preteen girls 9-13 yrs- regardless of HIV status Recommended for all HIV-infected adult men (MSM) & women, Can be given regardless of CD4+ count, ART use or viral load Regimen dose month 0, 2, 6 (pre-teen month 0, 6 (2 doses)) Cevarix (HPV 16,18) R Gardasil (HPV 6,11,16,18) prevents approx 90% of warts (only in private sector) Gardasil might reduce existing warts (JAMA Dermatol. 2015;151(12): ) S Afr J HIV Med 2018; 19(1)

28 Condylomata acumiata Let s advocate to vaccinate men and women with quadrivalent HPV vaccine

29 Conclusion There are opportunities to expand immunization for HIV-infected Adolescents & Adults Vaccinate during stable disease Communicate with patients about the importance of vaccination and the availability of vaccines Vaccination is the most cost effective intervention of 21 st century