Bedell, R

Braker, K

Chan, Keith

Elema, R

Hogg, R

Klarkowski, D

Mills, C

O'Brien, Daniel P

Olaiya, M

Shanks, L

Tu, D

Verputten, M

English

MSF Field Research

Field testing of World Health Organization (WHO) 2003 recommendations for initiating anti-retroviral therapy 
(ART) where CD4 is not available revealed low sensitivity among Stage I and II patients; a combination of 
Automated Total Lymphocyte Count (TLC) and Haemoglobin (Hgb) can ration the referral for CD4 testing.
Keith Chan1, D Tu2, D Klarkowski3, D O’Brien3, C Mills3, R Elema8, M Verputten3, R Bedell4, M Olaiya5, K Braker6, L Shanks7, RS Hogg1
1BCCfE, Vancouver, Canada, 2MSF Canada, Vancouver, Canada, 3MSF Holland, Amsterdam, Netherlands, 4Consultant Physician, Vancouver, Canada, 
5General Hospital Lagos, Lagos, Nigeria, 6MSF Germany, Berlin, Germany, 7MSF Holland, Goma, DRC, 8MSF Holland, Nchelenge, Zambia
www.msf.ca/aids2006
Table 1.  Stage stratified by CD4 
 CD4  <200 200<CD4<350 CD4>350  Total 
Stage I  160 79 121  360 
Stage II  61 25 22  108 
Stage I or II  221  104  143  468 
 
Table 2.  CD4, TLC, and Hgb summaries and correlation with CD4 among Stage I and II  
                 patients.  
 CD4    TLC  HgB 
Median  (IQR)  203 cells/ml  
( 88-371 ) 
1500 cells/ml   
( 1000-2090) 
10.5 g/dl  
(9.0-11.6) 
Correlation with CD4   1.0 0.38  0.16 
 
Table 3.  Comparison of CD4 based criteria for initiating ART with various TLC based criteria  
                 among Stage I and II patients (N=468).  
  Starting 
ART   CD4<350 CD4>350 Sensitivity    Specificity PPV  NPV accuracy
Total     325  143           
CD4 < 350 
based  325 325  0  1.00  1.00  1.00  1.00 1.00 
WHO 2003 
(Stage II & 
TLC<1200) 
31 30  1  0.09  0.99  0.97  0.32 0.37 
TLC < 1200  160 149  11  0.46  0.92  0.93  0.43 0.60 
TLC < 1400  205 185  20  0.57  0.86  0.90  0.47 0.66 
TLC < 1600  259 220  39  0.68  0.73  0.85  0.50 0.69 
TLC < 1800  303 249  54  0.77  0.62  0.82  0.54 0.72 
TLC < 1900  327  262  65  0.81  0.55  0.80  0.55 0.73 
TLC < 2000  336 266  70  0.82  0.51  0.79  0.55 0.72 
TLC < 2500  413 303  110  0.93  0.23  0.73  0.60 0.72 
TLC < 3000  435 312  123  0.96  0.14  0.72  0.61 0.71 
*Accuracy = (true positives + true negatives)/ (total number of patients)  
 
 
In our study population, by using this method 100% of those in Stage I or II with a 
CD4<200 would receive CD4 testing as would most of those with a CD4<350.  In 
this way, only 54% (204/375) of Stage I or II patients would require baseline CD4 
monitoring resulting in a significant reduction in the total utilization of CD4 testing.
Due to the lack of precision of manual TLC measurements, the conclusions of 
this study are limited to those sites with access to automated TLC testing.
This analysis reinforces the need for improved access to CD4 testing to HIV positive 
patients living in SSA and demonstrates the shortcomings of the current 2003 WHO 
recommendations.
Conclusions
This analysis shows that many patients in Sub-Saharan Africa present for HIV care 
when they are still asymptomatic, and up to 69% of these at baseline have CD4 
counts in the range where ART is indicated.  The 2003 WHO guidelines performed 
very poorly with respect to identifying stage I or II patients eligible for ART based on 
a CD4 count criteria of <350 or <200 (sensitivity of 9% and 11% respectively).  For 
our study population, if CD4 testing were not available, recommending ART for both 
stage I and II patients with a TLC<1200 would result in five fold increase in the 
number of these patients receiving ART (160 vs. 31) with a minimal increase in the 
absolute number of patients started on ART with a CD4>350 (11 vs. 1). 
For regions where CD4 testing is available but access is limited by distance or cost, 
baseline CD4 testing could be restricted to those in Stage III, IV, and those in Stage 
I or II with a TLC<1400 or those in Stage I or II with an intermediate TLC (1400 -
1900) and a Hgb<11. 
Background
Many regions lack access to CD4 testing which may limit appropriate access to ART.  
Where CD4 testing is unavailable the 2003 WHO guidelines recommend initiating 
ART among Stage III and IV patients and among Stage II patients with a 
TLC<1200cells/ml.
Results
468 ART naive subjects (98 from DRC, 217 from Nigeria, 153 Zambia) had CD4 and 
TLC measurements within 6 months of entry into the study. Two hundred and twenty 
one (47%) had a CD4<200 and 325 (69%) had a CD4<350.   49% of patients with a 
CD4<350 had TLC<1200.
The sensitivity and specificity of the 2003 WHO recommendations among Stage I 
and II patients for detecting a CD4<350 was 9% and 99%, respectively. Including all 
Stage I patients with a TLC<1200 improved sensitivity by 37% (allowing 43% of 
patients to be correctly identified), with only a 7% drop in specificity.  A model 
utilizing a TLC<1400 combined with a cut off of Hgb<11 to rule in subjects with an 
intermediate TLC between 1400 and 1900 provided optimal accuracy, capturing 
83% of those with a CD4<350.  This model also had a 100% sensitivity for detecting 
patients with a CD4<200.
Methods
An analysis was conducted using anonymous patient data from projects in 
Nchelenge, Zambia; Lagos, Nigeria; and South Kivu, DRC.  Eligibility for ART 
according to 2003 WHO guidelines using clinical stage and TLC was compared to 
CD4 based criteria. Various TLC and Hgb thresholds were examined to optimize 
sensitivity and specificity among Stage I and II patients for detecting a CD4<350.
Objectives
To assess the field performance of WHO recommendations specifically on Stage I or 
II patients and explore alternate models for initiating ART or rationing CD4 testing 
based on TLC and Hgb. 
Table 4.  Comparison of CD4 based criteria for initiating ART with various TLC and Hgb based criteria among Stage I and II patients (N=375).  
         CD4<200 cut off        CD4<350 cut off       
   Starting 
ART   CD4<200 200<CD4<350 CD4>350 Sensitivity Specificity PPV  NPV  accuracy Sensitivity    Specificity PPV NPV accuracy
Total   168  91  116                     
                             
TLC < 1200  120 90  22  8  0.54  0.86  0.75  0.69  0.71 0.43  0.93  0.93 0.42 0.59 
TLC < 1200 or TLC 
[1200,2200)+hg<11  205 120  47  38  0.71  0.59  0.59  0.72  0.65 0.64  0.67  0.81 0.46 0.65 
                             
TLC < 2000  262 146  63  53  0.87  0.44  0.56  0.81  0.63 0.81  0.54  0.80 0.56 0.73 
TLC < 2000 or TLC 
[2000,3000)+hg<11  307 158  76  73  0.94  0.28  0.51  0.85  0.58 0.90  0.37  0.76 0.63 0.74 
                             
TLC < 1400  157 104  37  16  0.62  0.74  0.66  0.71  0.69 0.54  0.86  0.90 0.46 0.64 
TLC < 1400 or TLC 
[1400,1900)+hg<11  247  168  47  32  1.00  0.62  0.68  1.00  0.79  0.83  0.72  0.87 0.66 0.80 
 

Field testing of World Health Organization (WHO) 2003 recommendations for initiating anti-retroviral therapy (ART) where CD4 is not available revealed low sensitivity among stage I and II patients; a combination of Automated Total Lymphocyte Count (TLC) and Haemoglobin (Hgb) can ration the referral for CD4 testing.

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