Utility of total lymphocyte counts, haemoglobin and body mass index in determining eligibility for A

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Utility of total lymphocyte counts, haemoglobin
and body mass index in determining eligibility
for ART in rural Uganda

• David Moore1,2,3A Awor1, R Downing1, W Were1,
• P Solberg1, D Tu4, K Chan2,, RS Hogg2, J Mermin1

• Global AIDS Program, US Centers for Disease
  Control and Prevention, Entebbe, Uganda
• British Columbia Centre for Excellence in
  HIV/AIDS, Vancouver, Canada
• Department of Medicine, Faculty of Medicine,
  University of British Columbia, Vancouver, Canada
• Medecins Sans Frontieres Holland, Amsterdam,
  The Netherlands

The findings and conclusions in this
presentation are those of the authors and do not
necessarily represent the views of the Centers
for Disease Control and Prevention."
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Background

• Eligibility for ART is usually determined with
  CD4 count testing clinical staging
• However, CD4 counts not widely available in
  sub-Saharan Africa
• Clinical staging alone has poor sensitivity for
  low CD4 counts
• Total lymphocyte counts (TLCs) have been studied
  as an alternative to CD4 counts

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Background

• TLCs are highly correlated with CD4s
• Do not accurately identify low CD4 counts
• Hb improves accuracy of TLCs
• Spacek et. al US Ferris et. al. S. Africa
• Limited data from tropical African countries
• Previous studies have viewed treating subjects
  with CD4s gt 200 cells/ µL as undesirable

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Study objectives

• To develop clinical algorithms using TLCs, Hb,
  and BMI to identify pts who require ART
• To use more flexible definitions of CD4
  thresholds based on 2006 WHO guidelines for ART

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Methods

• Baseline data from the Home Based AIDS Care
  project (HBAC) in Tororo, Uganda
• Participants were HIV-infected adults assessed
  for ART-eligibility
• WHO clinical stages I, II or III only

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Data analysis

• 2 x 2 tables used to derive TLCs assoc with CD4
  counts 350 cells/ µL
• Models evaluated for accuracy
• True Pos True Neg / all subjects
• Maximize sensitivity for CD4s 200 cells µL.
• Minimize number offered ART with counts gt 350
  cells/ µL (false positives)
• Acceptable to offer ART or to defer for CD4s btwn
  200 350 cells/ µL

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Algorithm construction

• TLCs used to define upper and lower thresholds to
  exclude and include subjects for ART
• ART eligibility for those with intermediate TLCs
• Hb thresholds of 11 or 12 g/dL
• and/ or
• BMI thresholds of 18, 19 and 20 kg/m2.

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Results

• 1944 presented for assessment
• 104 (5.2) were excluded because of stage IV
  disease
• 1785 subjects included in analysis.
• 75.2 were women
• Median CD4 counts 235 cells/µL
• Median TLCs 1840 cells/µL.

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Performance of TLC thresholds in predicting CD4
cell counts 350 cells/ µL
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TLC combined with Hb and BMI
Model 1
Total lymphocyte count
TLC 2000
TLC 2000 - 3000
TLC gt 3000
Examine Hb and BMI
ART eligible
Defer treatment
Hb 11 or BMI 18
Hb gt 11 and BMI gt18
ART eligible
Defer treatment
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TLC combined with Hb alone
Model 2
Total lymphocyte count
TLC 2000
TLC 2000 - 3000
TLC gt 3000
Examine Hb
ART eligible
Defer treatment
Hb 11g/ dL
Hb gt 11 g/dL
ART eligible
Defer treatment
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Model performance

• TLC threshold of 2250 cells/ µL alone
• accuracy of 0.73,
• sensitivity of 0.88
• false positive ratio of 0.21
• TLC 2000 3000, with BMI 18 or Hb 11
• accuracy of 0.75
• sensitivity of 0.90
• false positive ratio of 0.22
• TLC 2000 3000, with Hb 11
• accuracy of 0.75,
• sensitivity of 0.88
• false positive ratio of 0.18

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Conclusions

• TLC threshold of 2250 cells/ µL
• 88 sensitivity for CD4s lt 200 cells/µL
• 21 of treated subjects with CD4s gt 350.
• Hb and BMI only marginally improved model
  accuracy
• However, Hb and BMI may still be of value in
  determining ART eligibility in resource-limited
  settings.

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Conclusions

• Anemia and low BMI are independent risk factors
  for early mortality on ART in African settings
• (Etard J et. al. Sinkala M CROI 2006)
• While TLCs may not directly correlate with CD4
  values, they are equally associated with
  mortality on ART
• (Bedell et. al Antivir Ther 2003)
• Development of ART eligibility criteria using
  TLCs, Hb and BMI may be more applicable and
  relevant in rural African settings.

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Acknowledgements

• Participants in the Home-Based AIDS Care project.
  
• Field officers, counselors and clinical staff who
  care for patients in the Home Based AIDS Care
  project
• Informatics team at CDC-Uganda
• Ugandan Ministry of Health
• The AIDS Support Organization
• PEPFAR