Depressed CD4: Is it always HIV

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Depressed CD4 Is it always HIV?

• Aaron J. Loeb, BSN, RN
• Celine Hanson, MD
• Texas Childrens Hospital12-14-2006

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Objectives

• Case Presentation
• Emerging Trends
• Syphilis and HIV
• Disease Management
• CD4 function
• Infectious Diseases and CD4
• CD4 testing/guidelines
• Counseling

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CASE PRESENTATION
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Case Presentation

• Clinical History
• 30 year old HIV negative male with progressive
  rash
• Excess fatigue and sleepiness
• Topical/lotions use
• Denied fever, headache, itching

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CD4 Testing
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HIV Rapid Testing

• Results
• 05/05 Negative
• 12/05 Negative
• 01/06 Negative
• 04/06 Negative
• 09/06 Negative

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Case Presentation

• Physical Examination
• Fixed macular, reddish-brown rash
• Central presentation with progression to
  extremities
• Rash highlighted with temperature change
• No alopecia, lymphadenopathy or pharyngitis

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Case Presentation

• Diagnosis/Treatment
• Clinical secondary syphilis confirmed by reactive
  RPR (1128)
• IM Pen G administration
• Jarisch-Herxhemiers reaction following
  penicillin delivery

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Case Presentation

• Counseling
• Contact by local Health Department
• Possible co-infection with HIV
• Contagious avoid sexual encounters
• Relevance lowered CD4 to syphilis

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Emerging Trends

• Syphilis and HIV

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History of Syphilis

• Naples
• First well recorded outbreak in 1494
• CDC began tracking in 1941
• Previous Names
• Great Pox
• The French Disease
• The English Disease

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Syphilis Demographics Summary
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Cities with Highest Reported Rates of PS
Syphilis, 2004
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Primary and Secondary Syphilis Rates

• The South
• Increased 3.1 versus 3.6 cases per 100,000
  population a 16 increase
• Men
• Increased from 2.6 to 4.7 during 2001-2004
• Blacks 5.1 times higher than whites in 2003 and
  5.6 times higher in 2004
• Women
• Remained at 0.8 in 2004
• Decreased from 1.7 to 0.8 from 2000 to 2003

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Syphilis Co-Infection with HIVHarris County
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Disease Management

• CD4 function and HIV
• Other Infectious Diseases and CD4
• CD4 testing/guidelines
• Counseling

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Disease Management

• CD4 function and HIV

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The Immune System

• The National Cancer Institute at Frederick
• Protects against infectious pathogens
• Mechanism of protection
• Innate--natural or native immunity
• Adaptive--acquired or specific immunity

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CD4 Function

• Delayed T cell hypersensitivity responses
• Influence other immune cell activity
• Immunoglobulin synthesis
• Cellular cytotoxicity

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HIV Replication

• CD4 as a high affinity receptor
• - gp120 attaches to CCR5 and CXCR4
• - gp41 insertion through cell membrane
• Stages
• - Acute retroviral
• - Middle, chronic phase
• - Full-blown AIDS
• Macrophages and monocytes vulnerable

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Impact of HIV on CD4

• Precise mechanism for CD4 loss in HIV disease is
  not defined
• Potential mechanisms for CD4 loss include
• HIV CD4 cells home to the lymph system
• Due to CD62 homing ligand receptor and Fas
  upregulation after HIV binding to CD4
• Signaling to CD4/HIV infected cells leads to
  programmed cell death (apoptosis) in lymph tissue
• Naïve CD4 T cells are depleted more rapidly in
  the thymus than memory cells
• Results in impaired supply of CD4 T cells to
  periphery
• Increases division rate of naïve T cells and
  lowers emigration out of the thymus

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CD4 and HIV viral loadRisk for AIDS (25 y/o)
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Syphilis and CD4

• Syphilis without HIV infection
• Independent of gender CD4 decreases as CD8
  increases
• Syphilis with HIV infection
• CD4 count decreases with increased viral load of
  primary and secondary syphilis
• CD4 count increases with syphilis treatment with
  decreased HIV-RNA counts

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Disease Management

• Infectious Diseases and CD4

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Infections that lower CD4 or CD4/CD8 ratio

• Tuberculosis (TB)
• Cytolomegalovirus (CMV)
• Herpes Simplex Virus (HSV)
• Epstein Barr Virus (EBV)

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CD4 and TB

• T cell apoptosis has been described in HIV
  negative individuals with disseminated TB
• Affected cells include CD4 and CD8 T cells
• Individuals with extrapulmonary TB and/or more
  severe complications are more likely to have
  lower CD4 T cells

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CD4 and Viral infectionsCMV, HSV and EBV

• CD4 and CD8 T cells and neutralizing antibody
  are pivotal in human responses to primary viral
  infections
• CD8 T cell expansion is typical in symptomatic
  CMV infection and causes an inverted CD4/CD8
  ratio
• Inverted CD4/CD8 ratio is not aytpical in HSV or
  EBV
• Peripheral blood CD4 depletion rarely occurs in
  CMV infection
• Diminished CMV specific CD4 cells has been
  documented in pediatric CMV

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Screening for Syphilis

• Syphilis Elimination Plan (SEE)
• CDC formed campaign in 1999
• Improve testing and laboratory services
• Goal make a rapid test available for use in the
  U.S. within the next few years
• Current testing RPR
• Week waiting period
• Target HIV testing sites

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Centers For Disease Control HIV Guidelines

• Revised September 2006
• There is an urgent need to increase the
  proportion of persons who are aware of their
  HIV-infection status
• Expanded, routine, voluntary, opt-out screening
  in health care settings is needed
• Such screening is cost-effective
• Bernard Branson MD Revised Recommendations for
  HIV Testing in Healthcare Settings in the U.S.

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Disease Management

• Testing/Guidelines
• Clinical lymphocyte subset testing provides most
  accurate results when consistent laboratory is
  used
• Dual (CD3/CD4) and triple antibody staining
  (CD3/CD4/CD45) have eliminated inclusion of cells
  from other lineages
• Single test assessment should be avoided
• Repeat testing using specimens collected at
  separate dates

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Disease Management

• Counseling patients with CD4 depression

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Counseling Considerations

• Counseling for depressed CD4 count
• History of HIV risks
• Recommend HIV testing
• Consider other STDs and impact on CD4 test
• History for STDs
• Recommend syphilis, TB or viral testing
• Consider other immune deficiencies
• Idiopathic CD4 T cell lymphocytopenia

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Screening For HIV

• High rates of non-return for test results
• In 2000, 31 did not return for results of
  HIV-positive conventional tests at publicly
  funded sites
• HIV rapid testing availability is crucial
• -Sure Check and Stat Pak approved in May 2006
• Screen for high prevalence and high volume
  settings
• Bernard Branson MD Revised Recommendations for
  HIV Testing in Healthcare Settings in the U.S.

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Testing for HIV

• Recommendations for Adults and Adolescents
• Routine, voluntary HIV screening for all persons
  13-64 in health care settings, not based on risk
• Repeat HIV screening of persons with known risk
  at least annually
• Opt-out HIV screening with the opportunity to ask
  questions and the option to decline
• Include HIV consent with general consent for
  care separate signed informed consent not
  recommended
• Prevention counseling in conjunctions with HIV
  screening in health care settings is not required
• Bernard Branson MD Revised Recommendations for
  HIV Testing in Healthcare Settings in the U.S.

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Counseling Challenges

• Identifying high risk behavior
• Educate about mode of transmission
• Possibility of reinfection
• Co-infection with HIV
• Correlating possible exposure to syphilis
  exposure

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Article References

• Antas, P.R., Ding, L., Hackman, J.,
  Reeves-Hammock, L., Shintani, A.K., Schiffer, J.,
  Holland, S.M., et al. (2004). Decreased CD4
  lymphocytes and innate immune responses in adults
  with previous extrapulmonary tuberculosis.
  Journal of Allergy Clinical Immunology 117(4).
• Fan, Y.M., Zeng, W.J. Li, S.F. (2004).
  Immunophenotypes, apoptosis, and expression of
  Fas and Bcl-2 from peripheral blood lymphocytes
  in patients with secondary early syphilis.
  Sexually Transmitted Diseases. 31(4).
• Gamadia, L.E., Rentenaar, R.J., Van Lier, R.A.,
  Berge, I.J. (2004). Properties of CD4 () T cells
  in human cytomegalovirus infection. Human
  Immunology. 65 (5).
• Grossman, Z., Paul, W.E. (2000). The impact of
  HIV on naïve T-cell homeostasis. Nature Medicine
  (6)
• Hatton, A.E., Montamat-Sicotte, D., Gudgeon, N.,
  Rickinson, A.B., McMichael, A.J. Calian, M.F.
  (2003). Characteristics of the CD4 T cell
  response to Epstein-Barr virus during primary and
  secondary infection. Journal of Expert Medicine
  198(6).
• Kofoed, K., Gerstoft, J. Mathiesen, L.R.,
  Benfield, T. ( 2006). Syphilis and human
  immunodeficiency virus (HIV)-1 coinfection
  influence on CD4 T-cell count, HIV-1 viral load,
  and treatment response. Sexually Transmitted
  Diseases. 33(3).
• MMWR, (2006). Primary and Secondary Syphilis
  ---United States, 2003-2004. MMWR Weekly. 55(10),
  pp 269-273.

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Website References

• AIDS Info
• http//www.aidsinfo.nih.gov/
• Centers for Disease Control, HIV
• http//www.cdc.gov/hiv/
• Centers for Disease Control, Syphilis
• http//www.cdc.gov/std/syphilis/default.htm
• Texas Department of State Health Services, HIV
• http//www.dshs.state.tx.us/hivstd/info/default.sh
  tm
• Wikipedia, treponema pallidum
• http//en.wikipedia.org/wiki/Treponema_pallidum

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Would like to thank

• Dr. Celine Hanson
• Dr. William T. Shearer
• Chivon McMullen-Jackson
• Study Participant