Viral load, CD4 cell counts and antibodies:

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Viral load, CD4 cell counts and antibodies What
do we know and what does it all mean? Brian
Williams, SACEMA, November 2007
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We have not succeeded in answering all your
problems. The answers we have found only serve to
raise a whole set of new questions. In some ways
we feel that we are as confused as ever but we
believe that we are confused on a higher level
and about more important things. Notice at the
Cambridge University Computer Centre Surgery,
1970.
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The standard model
Viral load
CD4
Time
Time
Acute phase weeks Final phase
months Interested in the long chronic phase 10
yrs
Antibodies
Time
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Viral load and CD4 cell counts
Virions/mL
CD4 cells/mL
Orange Farm, South Africa. (Auvert et al. PLOS
Medicine, 2005)
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Viral load and CD4 cell counts
10,000
1000
100
Virions/mL
10
1
0.1
0.01
CD4 cells/mL
Orange Farm, South Africa. (Auvert et al. PLOS
Medicine, 2005)
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CD4 cell count decline for different viral loads
Rodriguez et al. Jama, 2006.
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Antibody concentration and CD4 cell counts
? Up to 2000
CD4 cells /mL
Optical density ? log(antibody concentration)
ZVITAMBO (Hargrove, pers. comm.)
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Quite solid relationships buried in a vast amount
of noise... 1. What does the underlying
relationship imply? 2. Where does the noise come
from? Problem We have lots of cross-sectional
data but little time series data
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Viral load distribution Young men in Orange
Farm, South Africa
Frequency
0.01 0.1 1
10 100 1000 10,000
Viral load/mL
Orange Farm, South Africa. (Auvert et al. PLOS
Medicine 2005)
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CD4 cell counts in HIV-positive and HIV-negative
people
Orange Farm, South Africa. (Auvert et al. PLOS
Medicine 2005) Zambia (Kelly et al. Acta Tropica
2002)
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Log antibody distribution Harare
Frequency
Optical density i.e. ln(antibody concentration)
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Combine the individual decline with the initial
distribution
2000
Assume that survival is independent of the
initial value of the CD4 cell count
CD4
1000
CD4 cells/?l
500
HIV
0 10
20 Time (years)
Survival
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Assume that survival is independent of the
initial value of the CD4 cell count
CD4
Time
CD4 in HIV
Log(Initial viral load) sets survival
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CD4 cell counts in HIV-positive and HIV-negative
people
Orange Farm, South Africa. (Auvert et al. PLOS
Medicine 2005) Zambia (Kelly et al. Acta Tropica
2002)
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Distribution of CD4 cell count decline
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Survival of young men in Orange Farm, South
Africa?
Survival (yrs) 42.2 6.5?log10(VL/mL)
Viral load Weibull survival
Frequency
Time years
Orange Farm, South Africa. (Auvert et al. PLOS
Medicine 2005)
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So we need to explain why
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Survival against age at HIV seroconversion
Proportion surviving
Years since infection
Time from HIV-1 seroconversion to AIDS and death
before widespread use of highly-active
anti-retroviral therapy A collaborative
re-analysis. Cascade Collaboration. Lancet
2001355 1131?1137
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Prevalence
Lusaka
Incidence
Gauteng
Death
00
00
05
10
40
05
95
95
10
90
90
40
20
Lusaka
Gauteng
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