Prevention of Opportunistic Infections

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Prevention of Opportunistic Infections
Immunizations in HIV-Infected Adults

• Ayesha Mirza M.D., F.A.A.P.
• Assistant Professor
• Department of Pediatrics, University of Florida,
  Jacksonville

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Disclosure of Financial Relationships

• This speaker has no significant financial
  relationships with commercial entities to
  disclose.

This slide set has been peer-reviewed to ensure
that there areno conflicts of interest
represented in the presentation.
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Prevention of Opportunistic Infections
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Some Basic Concepts

• While HAART has changed the way we manage HIV,
  prevention of infections remains an integral part
  of care
• Prevention consists of using medications for
  prophylaxis when indicated by CD4 count number
• Vaccines play a vital role in preventing
  infections as well

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• available _at_ www.tulane.edu/dmsander/WWW/MBChB/4b.
  html

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• Opportunistic infections in patients with aids
  admitted to an university hospital of the
  Southeast of Brazil Rev. Inst. Med. trop. S.
  Paulo vol.45 no.2 São Paulo Mar./Apr. 2003

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Pneumocystis Pneumonia (PCP)

• Recently renamed Pneumocystis jiroveci
• Primary prophylaxis recommended for anyone with
  200 CD4 cells/µl or oropharyngeal Candida
  infection
• Primary prophylaxis may be discontinued if CD4
  count gt 200 cells /µl for 3 months

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• Trimethoprim-sulfamethoxazole is the preferred
  drug.
• Other options include dapsone, aerosolized
  pentamidine, atovaquone, clindamycin with
  primaquine
• Prophylaxis may be considered for those who have
  a CD4 percentage of lt14 or a history of an AIDS
  defining illness but do not qualify otherwise

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• Secondary prophylaxis is recommended for h/o
  prior PCP pneumonia
• Secondary prophylaxis may be discontinued when
  CD4 count has been gt 200 cells/µl for 3 months
  as a result of HAART
• Re-initiate primary or secondary prophylaxis if
  CD4 counts lt 200 cells/µl

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Dosages for Antimicrobial Prophylaxis for PCP

• TMP/SMX DS 1 tab po once daily or MWF
• Dapsone 100mg/d
• Aerosol pentamidine 300mg/month
• Atovaquone 1500 mg/d

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Toxoplasmosis

• Prophylaxis recommended if Toxoplasma IgG
  positive and CD4 lt100 cells/µl
• Discontinue once CD4 count gt 200 cells/µl for 3
  months
• Trimethoprim-sulfamethoxazole preferred (TMP/SMX
  DS 1 tab po once daily)
• Alternatives include dapsone pyrimethamine
  leucovorin or atovaquone pyrimethamine
  leucovorin

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• Secondary prophylaxis should be initiated after
  h/o prior Toxoplasma encephalitis
• May be discontinued when CD4 counts are gt 200
  cells/µl for a sustained period (i.e.gt 6 mths)
  and the pt has successfully completed initial
  therapy and is asymptomatic for Toxoplasma
• Secondary prophylaxis re-initiated if CD4 count
• lt 200 cells/µl

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Mycobacterium Avium Complex Disease (MAC)

• Prophylaxis recommended when CD4 cell count
• lt 50 cells/µl
• Can discontinue once CD4 counts gt100 cells/µl for
  3 months
• Treatment choices include azithromycin 1200 mg/wk
  or clarithromycin 500 mg bid or rifabutin 300 mg/d

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• Secondary prophylaxis recommended for documented
  disease
• This may be discontinued when CD4 gt 100 cells/µl
  for 6 months, patient has completed 12 months
  of therapy and is asymptomatic
• Re-initiate secondary prophylaxis if CD4 count lt
  100 cells/µl

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Other Opportunistic Infections

• HIV-infected persons may also be at increased
  risk for acquiring Tuberculosis, Cytomegalovirus,
  opportunistic fungal infections e.g.
  histoplasmosis, coccidiodomycosis, cryptococcosis
  
• No specific primary prophylaxis is recommended

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Cryptococcosis

• Secondary prophylaxis recommended for documented
  disease with fluconazole
• This may be discontinued when CD4 counts gt
  100-200 cells/µl sustained (e.g. 6 months) and
  completed initial therapy and asymptomatic
• Re-initiate secondary prophylaxis for CD4 count
  lt100-200 cells/µl

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Cytomegalovirus Disease

• Secondary prophylaxis after documented end organ
  disease
• May be discontinued when CD4 count gt 100-150
  cells/µl sustained (e.g. 6 months) and no
  evidence of active disease.
• Re-initiate when CD4 counts lt 100-150 cells/µl
• Preferred drugs valganciclovir, ganciclovir,
  foscarnet

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Immunizations inHIV Infection
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Immunizations

• All vaccines may not be immunogenic and safe
• Different schedules and doses may be required
• Need to consider household members when giving
  vaccines as well
• In general inactivated vaccines are safe while
  live vaccines are not
• Attenuated vaccines may be safe in certain
  circumstances

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Immunizations

• Better to immunize when CD4 counts high and
  immune response good
• Administer a safe vaccine even if not sure about
  immunogenicity
• For vaccines without specific studies in
  HIV-infected individuals consider risk benefit
  ratios

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http//www.cdc.gov/mmwr/pdf/wk/mm5641-Immunization
.pdf-accessed March 14, 2008
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Tetanus, Diphtheria Pertussis Vaccine

• Should be given routinely to HIV infected
  individuals
• A Td booster is recommended every ten years
• In addition, one dose of Tdap should be
  substituted for Td
• Two Tdap vaccines available Boostrix-given up
  to 18 years of age and Adacel up to 64 years of
  age

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Tetanus, Diphtheria Pertussis Vaccine

• Tdap is recommended for those less than 65 years
  of age
• Can be given as early as 2 years after receiving
  last Td vaccine
• During pregnancy Td should be used during the 2nd
  or 3rd trimester if gt 10 yrs since last booster,
  Tdap may be given in the post partum period

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Human Papilloma Virus (HPV) Vaccine (Gardasil)

• Prophylactic, quadrivalent three dose vaccine
  containing types 6, 11, 16 and 18
• Only approved for women so far
• Resolution of infection requires an effective
  immune response
• HIV-infected women double the risk of HPV
  infection compared to non HIV-infected women with
  similar risk factors

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• HPV Vaccine Why Should We Vaccinate?

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HPV Vaccine

• Vaccine is recommended for use prior to onset of
  sexual activity but can be given afterwards as
  well
• Prevents infection by inducing neutralizing
  antibodies against HPV capsid proteins L1 and L2
• The vaccine contains virus like particles that
  mimic the viral capsid antigen but does not
  contain any viral DNA

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• Dosage same as non HIV-infected individuals
• 3 dose schedule at 0, 2 and 6 months
• Vaccine trial underway to determine
  immunogenicity in HIV-infected children
• Not recommended for use during pregnancy
• Male studies also underway

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Measles, Mumps and Rubella Vaccine

• Immunization is recommended except for those who
  are severely immunocompromised i.e. CD4 lt 200
  cells/µl
• One or two doses may be necessary for those with
  CD4 counts gt200 cells/µl and no evidence of
  immunity
• Persons living in households with HIV infected
  persons should be vaccinated unless they are also
  severely immunocompromised
• Persons born before 1957 are considered immune

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Zoster Vaccine (Zostavax)

• FDA approved in 2006 for use in persons aged 60
  years or older
• Live attenuated varicella-zoster virus vaccine
  with a viral titre five times greater than the
  chicken pox vaccine.
• Contraindicated in HIV-infected individuals

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Varicella Vaccine (Varivax)

• Varicella highly contagious disease
• Secondary attack rates up to 90 amongst
  susceptible household contacts
• Both humoral and cell mediated immunity important
  in immune response
• Vaccine is contraindicated in children with CD4
  counts lt 15 and adolescents and adults with CD4
  count lt 200 cells/µl

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Varicella Vaccine

• Varicella vaccine may be considered for
  HIV-infected adolescents and adults without
  evidence of immunity with CD4 counts gt200
  cells/µl
• The dosage recommended would be 2 doses 3 months
  apart
• The vaccine is contraindicated during pregnancy
• May be given to nursing mothers without evidence
  of immunity
• Household contacts of immunocompromised patients
  should be routinely vaccinated

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Evidence of Immunity-Varicella

• Documentation of 2 doses of vaccine at least 4
  wks apart
• U.S. born before 1980 (except for health care
  workers and pregnant women)
• h/o varicella based on diagnosis or verification
  of varicella by a health care provider
• h/o zoster based on health care provider
  diagnosis
• Lab evidence of immunity or confirmation of
  disease

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Influenza

• Inactivated influenza vaccine is recommended for
  all individuals with HIV infection regardless of
  their immunologic status
• Influenza vaccine can and should be given during
  pregnancy
• Live attenuated influenza vaccine should not be
  given to individuals with HIV infection or their
  contacts

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Influenza Vaccine Dosage Recommendations

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Influenza Vaccine

• Results of a recent study show that rates have
  gone up from 28.5 in 1990 to 41.6 in 2002
• This is still well below the 2010 Healthy People
  target of 60
• Results from this same study also showed that
  individuals with higher viral loads and lower CD4
  counts less likely to receive the vaccine
• Individuals on HAART were also more likely to
  receive influenza vaccine
• Predictors of Influenza immunization in
  HIV-infected patients
• in the United States, 1990-2002. JID 2007 196
  339-46

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Influenza Vaccine

• Immunize annually
• No effect on HIV viral load
• Immunize all household contacts and caregivers
  including staff
• Despite long standing recommendations, influenza
  vaccination rates have traditionally been poor

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Pneumococcal Vaccines

• PPS 23 (Pneumovax)
• All HIV-infected individuals gt 2 yrs
• Adults one booster after 5 yrs
• Safe and effective

• PCV7 (Prevnar)
• All children
• No studies in adults
• Safe
• May be useful in adults

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Pneumococcal Vaccines

• PPV 23
• 55-75 effective against invasive pneumococcal
  disease caused by vaccine serotypes
• Does not reduce carriage (no herd immunity)

• PCV7
• gt95 effective
• against invasive pneumococcal disease caused
  by vaccine serotypes
• Reduces carriage (herd immunity)

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Pneumococcal Vaccines

• PCV7
• Insufficient data to recommend

• PPS 23
• Recommended for CD4 gt 200 cells/µl
• Give if CD4 lt 200 cells/µl and repeat when CD4
  improves due to HAART

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Hepatitis A Vaccine

• Safe and effective
• Two dose schedule 0 and 6-12 months
• Particularly important to vaccinate if Hep B or
  Cco-infection, MSM
• Use Vaqta or Havrix not Twinrix since dose is
  lower

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Hepatitis B Vaccine

• Safe and effective
• Recommended for all HIV-infected persons except
  those who are HBsAg positive
• Response better if CD4 gt 200 cells/µl
• Check antibody levels after completion of 3 dose
  series
• If HBsAb lt10 mIU/ml repeat 3 dose series

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• Currently available vaccines include Recombivax
  and Engerix-B
• Dose for immunosuppressed hosts is double i.e. 40
  µg instead of 20 µg

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Quadrivalent Meningococcal Vaccine (Menactra)

• Contains serotype A, C, Y and W135
• Recommended in all adolescents including HIV-
  infected at increased risk of meningococcal
  infection i.e. anatomic or functional asplenia,
  terminal complement component deficiencies,
  travel to endemic areas, college students living
  in dorms and military recruits

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Vaccines not Frequently Used but Contraindicated
in HIV-Infected Adults

• Typhoid Ty21a
• Yellow Fever Vaccine
• Vaccinia (small pox vaccine)
• Oral polio vaccine

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Influenza

• A 29 y.o. HIV infected man on HAART with a CD4
  cell count of 150/µl presents in late November
  for a routine follow-up visit. Which of the
  following would you recommend regarding
  immunizing him against influenza?
• Give him inactivated influenza vaccine at this
  visit
• Wait and give him inactivated influenza vaccine
  after his CD4 cell count increases to gt 200/µl
• Give him live attenuated influenza vaccine due to
  better immune response to the vaccine

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Zoster Vaccine

• A 60 y.o. HIV-infected man on
  antiretroviral therapy with an undetectable HIV
  RNA level and CD4 cell count of 341/ µl wants to
  know if he should get the new shingles vaccine.
  Which one of the following would you recommend
  for him?
• Do not give the vaccine
• Give the vaccine if he has a negative varicella
  
• antibody titre
• Give the vaccine if he has a history of chicken
  pox or zoster

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Hepatitis Vaccine

• A 28 y.o woman with a CD4 cell count of 522/µl
  received her first 2 doses of hepatitis B vaccine
  on schedule approximately 1 year ago. She is lost
  to follow up for 9 months and now returns. What
  would you recommend regarding her hepatitis B
  immunization?
• Start over at the beginning
• Give 2 doses I month apart
• Give the final dose

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Tetanus Vaccines

• A 30 y.o HIV infected man with a CD4 count of
  450/µl comes in after cutting his hand on an old
  object. He received all his childhood vaccines
  but has not had a tetanus shot for at least 10
  years. Which of the following would you
  recommend?
• He should not receive tetanus vaccine because of
  his HIV infection
• He should receive the standard TD vaccine
• He should receive the Tdap vaccine

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Live Vaccines

• A 21 y.o woman with recently diagnosed HIV
  infection has a cell count of 122/µl. Which one
  of the following vaccines would be considered
  safe for her?
• Varicella vaccine
• Conjugate meningococcal vaccines
• MMR vaccine
• Oral polio vaccine

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Selected References

• Recommended Adult Immunization Schedule- United
  States, October 2007-September 2008. MMWR Oct 19,
  2007, Vol 56No 41
• Hepatitis A and B immunizations of individuals
  infected with human immunodeficeincy virus. Am J
  Med 2005, Vol 118 75S-83S
• Predictors of Influenza immunization in
  HIV-infected patients in the United States,
  1990-2002. JID 2007 196 339-46
• Prevention of Varicella. Recommendations of the
  Advisory Committee on Immunization Practices.
  MMWR Jun 22, 2007, Vol 56(RR04) 1-40
• Management of newly diagnosed HIV infection. N
  Eng J Med 2005 353 (16)1702-10