Access to CD4 Testing in ResourceLimited Settings:

1
IAS abstract WePe0068 August 2006
Access to CD4 Testing in Resource-Limited
Settings Impact of Clinical and Immunologic
Staging on Antiretroviral Eligibility in
MTCT-Plus Rabkin M, Katyal M, Carter RJ, Austin
J, Kim J, Toro P, El-Sadr WM, Abrams EJ and Nash
D International Center for AIDS Care
Treatment Programs (ICAP), Columbia University
Mailman School of Public Health, New York, United
States
INTRODUCTION
RESULTS
In resource-limited settings (RLS) without access
to CD4 enumeration, WHO clinical staging alone is
used to determine eligibility for antiretroviral
treatment (ART). We compared WHO stage and CD4
eligibility criteria in 6,136 adults enrolled in
Columbias MTCT-Plus Initiative. The MTCT-Plus
Initiative has established comprehensive
family-centered HIV care and treatment in RLS,
including 13 programs in sub-Saharan Africa and
Thailand (Figure 1). As of May 2006, 11,368
adults and children had been enrolled in
MTCT-Plus-supported programs.
Figure 4
Figure 5
The primary objective of the MTCT-Plus Initiative
is to provide care and treatment for HIV/AIDS to
families in RLS. In addition to reducing
mortality and morbidity, the Initiative hopes to
further reduce mother to child transmission of
HIV, to promote VCT and other prevention
strategies, to strengthen local health care
capacity, to decrease stigma and enhance support
for persons living with HIV/AIDS, to empower
patients, and to develop a generalizable model
for HIV/AIDS care in RLS (see www.mtctplus.org).
Figure 1 MTCT-Plus Programs
Figure 6
Figure 7
National and international guidelines support the
use of WHO clinical staging alone in settings
where CD4 enumeration is scarce or unavailable.
Expanding access to appropriate and affordable
CD4 testing is, however, a global priority.
MTCT-Plus protocols support regular clinical and
immunologic monitoring, enabling us to use these
data to assess the hypothetical impact of WHO
staging criteria alone vs. combined WHO staging
and CD4 counts.
METHODS
1,794 patients (29) met ART eligibility criteria
at baseline the median CD4 cell count for this
group was 134 (mean 134, IQR 78-178). An
additional 643 patients became eligible for ART
during follow up representing 16 cases/100 person
years of observation their median CD4 was 186
(mean 210, IQR 156-256). Overall, 8 of the 2,437
ART-eligible patients were eligible based on WHO
stage 4 alone. 78 were eligible based on WHO
stage 1-3 and CD4 lt 200. 14 were eligible based
on the combination of WHO stage 3 and CD4
201-350. Pregnant women eligible for ART at
enrollment were significantly less likely than
other women to be eligible on the basis of WHO
staging alone (5 vs. 9, p lt0.05). Older
patients were significantly more likely to be
ART-eligible at baseline and during follow up (p
lt 0.05).
Between 2/03 and 1/06, MTCT-Plus enrolled 6,656
ART-naïve adults in 9 countries 36 were
pregnant at the time of enrollment. Baseline WHO
staging and CD4 enumeration were followed by
ongoing clinical and immunologic monitoring WHO
stage was reassessed at each visit, and CD4
counts were requested twice-yearly. All MTCT-Plus
programs actually utilized the combination of
clinical staging and CD4 count to ascertain ART
eligibility, and programmatic eligibility
criteria were modified slightly in 2/05. For the
purposes of this analysis, however, we examine
the hypothetical use of WHO staging alone vs.
combined WHO staging and CD4 count, using the
following definitions of ART eligibility WHO
stage 4 irrespective of CD4 count WHO 3 and CD4
lt 350 and CD4 lt 200 irrespective of WHO stage.
We describe the proportion of patients eligible
for ART at the time of their baseline assessment.
We also describe the proportion of enrolled
patients who became eligible for ART during 4,110
patient-years of follow up (Figure 2) the median
time to eligibility was 33 weeks (IQR 10-62).

• Figure 2 Patients analyzed
• Baseline CD4 count is defined as a CD4 count
  no later than 6 weeks after enrollment.
• Baseline WHO stage is defined as WHO stage at
  the time of enrollment examination.
• Eligible for ART is defined as meeting one or
  more of the following criteria WHO stage 4 WHO
  3 plus CD4 lt 350 or CD4 lt 200.
• During follow up, participants were censored
  if/when the following occurred withdrawal from
  program, lost to follow up, no clinic visit in 6
  months, started ART prior to becoming eligible,
  death.

0
ART eligibility
Eligibility using WHO stage and CD4 count
RESULTS
Eligibility using WHO stage only
Cohort demographics are described in Figures 3-6.
83 of adults were female. 43 of women (36 of
the cohort) were pregnant at the time of
enrollment. The median age was 28 years (range
15-70) men were slightly older than women, with
a median age of 34 years. Median CD4 count at
enrollment was 351 cells/mm3 (IQR 196-542), with
significant differences between groups as
illustrated in Figure 4. Median baseline CD4 for
antepartum patients 344, for postpartum
patients 396, for female household members
221, and for male household members 266 (p lt
0.001). Overall, 63 of the cohort were WHO
stage 1 (WHO1) at enrollment, 20 were WHO2, 15
were WHO3, and 2 were
p lt 0.05
ART eligibility
ART eligibility
WHO4. As illustrated in Figure 5, the
distribution of WHO stages was significantly
different (p lt 0.001) between groups, with male
and female household members having more advanced
disease than the index women identified via pMTCT
programs. Figure 6 shows that 73 of patients in
WHO4 had CD4 lt 200 as did 16 of WHO1, 29 of
WHO2 and 54 of WHO3.
Figure 3

p lt 0.05
CONCLUSIONS
We reviewed the diagnoses that contributed to WHO
staging in the subset of 1,794 patients eligible
for ART at enrollment these are illustrated in
Figure 7. The most common stage-defining
diagnoses in WHO2 were minor mucocutaneous
manifestations (56), herpes zoster (34), and
weight loss (20). For WHO3, the most common
diagnoses included oral thrush (45), pulmonary
TB (28), weight loss (25), and fever (15). For
WHO4, the most common diagnoses included
extrapulmonary TB (26), wasting syndrome (22),
candidiasis (17) and Kaposis sarcoma (14).
92 of patients eligible for ART in this cohort
were identified using CD4 enumeration. Without
access to CD4 testing, these ART-eligible
patients would have been missed until they
developed WHO stage 4, a point at which treatment
may be less successful than that initiated
earlier in the clinical course of HIV/AIDS. While
the absence of CD4 testing should not by itself
delay the initiation of HIV/AIDS care and
treatment programs, or the prompt use of ART in
individual patients with advanced (stage 4)
disease, the availability of CD4 testing greatly
expands the ability to identify patients
requiring ART, especially among pregnant women.
The MTCT-Plus Initiative is funded by Bill
Melinda Gates Foundation, William and Flora
Hewlett Foundation, Robert Wood Johnson
Foundation, Henry J. Kaiser Family Foundation,
John D. and Catherine T. MacArthur Foundation,
David and Lucille Packard Foundation,
Rockefeller Foundation, Starr Foundation, US
Agency for International Development (USAID) We
would like to thank the staff at the MTCT-Plus
sites, participants in the programs, and John
Snow Inc.