FCAETC 2008 Fundamentals Prevention Opportunistic Infections by xl771209

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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

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 are no conflicts of interest represented in the presentation.

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

available @ www.tulane.edu/~dmsander/WWW/MBChB/4b.html

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

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 > 200 cells /µl for ≥ 3 months

• 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 <14 or a history of an AIDS defining illness but do not qualify otherwise

• Secondary prophylaxis is recommended for h/o prior PCP pneumonia

• Secondary prophylaxis may be discontinued when CD4 count has been > 200 cells/µl for ≥ 3 months as a result of HAART • Re-initiate primary or secondary prophylaxis if CD4 counts < 200 cells/µl

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

Toxoplasmosis
• Prophylaxis recommended if Toxoplasma IgG positive and CD4 <100 cells/µl • Discontinue once CD4 count > 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

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

Mycobacterium Avium Complex Disease (MAC)
• Prophylaxis recommended when CD4 cell count < 50 cells/µl • Can discontinue once CD4 counts >100 cells/µl for ≥ 3 months • Treatment choices include azithromycin 1200 mg/wk or clarithromycin 500 mg bid or rifabutin 300 mg/d

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

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

Cryptococcosis
• Secondary prophylaxis recommended for documented disease with fluconazole • This may be discontinued when CD4 counts > 100200 cells/µl sustained (e.g. ≥ 6 months) and completed initial therapy and asymptomatic • Re-initiate secondary prophylaxis for CD4 count <100-200 cells/µl

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

Immunizations in HIV Infection

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

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

http://www.cdc.gov/mmwr/pdf/wk/mm5641-Immunization.pdf-accessed March 14, 2008

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

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 > 10 yrs since last booster, Tdap may be given in the post partum period

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

HPV Vaccine: Why Should We Vaccinate?

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

• 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

Measles, Mumps and Rubella Vaccine
• Immunization is recommended except for those who are severely immunocompromised i.e. CD4 < 200 cells/µl • One or two doses may be necessary for those with CD4 counts >200 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

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

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 < 15% and adolescents and adults with CD4 count < 200 cells/µl

Varicella Vaccine
• Varicella vaccine may be considered for HIV-infected adolescents and adults without evidence of immunity with CD4 counts >200 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

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

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

Influenza Vaccine Dosage Recommendations
Vaccine
Fluzone ® (Sanofi-Pasteur)1 Fluvirin ® (Novartis)1 Fluarix® (GlaxoSmithKline)1 FluMist® (MedImmune)2
1. 2. Inactivated vaccines Live, attenuated vaccine

Dose Age Group (ml)
6-35 months 3-8 years ≥ 9 years 0.25 0.5 0.5

# of Doses
1 or 2 1 or 2 1

Contraindicated in HIV-infected individuals

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

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

Pneumococcal Vaccines
• PPS 23 (Pneumovax®) • All HIV-infected individuals > 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

Pneumococcal Vaccines
• PPV 23 • 55-75% effective against invasive pneumococcal disease caused by vaccine serotypes • Does not reduce carriage (no herd immunity) • PCV7 • >95% effective against invasive pneumococcal disease caused by vaccine serotypes • Reduces carriage (herd immunity)

Pneumococcal Vaccines
• PPS 23 • Recommended for CD4 > 200 cells/µl • Give if CD4 < 200 cells/µl and repeat when CD4 improves due to HAART • PCV7 • Insufficient data to recommend

Hepatitis A Vaccine
• Safe and effective • Two dose schedule: 0 and 6-12 months • Particularly important to vaccinate if Hep B or C co-infection, MSM • Use Vaqta® or Havrix® not Twinrix® since dose is lower

Hepatitis B Vaccine
• Safe and effective • Recommended for all HIV-infected persons except those who are HBsAg positive • Response better if CD4 > 200 cells/µl • Check antibody levels after completion of 3 dose series • If HBsAb <10 mIU/ml repeat 3 dose series

• Currently available vaccines include Recombivax® and Engerix-B®

• Dose for immunosuppressed hosts is double i.e. 40 µg instead of 20 µg

Quadrivalent Meningococcal Vaccine (Menactra®)
• Contains serotype A, C, Y and W135
• Recommended in all adolescents including HIVinfected 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

Vaccines not Frequently Used but Contraindicated in HIV-Infected Adults
• Typhoid Ty21a
• Yellow Fever Vaccine • Vaccinia (small pox vaccine) • Oral polio vaccine

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 > 200/µl Give him live attenuated influenza vaccine due to better immune response to the vaccine

1. 2. 3.

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?:
1. 2. 3. 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

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?:
1. 2. 3. Start over at the beginning Give 2 doses I month apart Give the final dose

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?:
1.
2. 3.

He should not receive tetanus vaccine because of his HIV infection He should receive the standard TD vaccine He should receive the Tdap vaccine

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?: 1. 2. 3. 4. Varicella vaccine Conjugate meningococcal vaccines MMR vaccine Oral polio vaccine

Selected References
1. Recommended Adult Immunization Schedule- United States, October 2007-September 2008. MMWR Oct 19, 2007, Vol 56:No: 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

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3. 4.

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