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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? ... Viral load. Weibull survival. 1. Survival is (almost) independent of ... – PowerPoint PPT presentation

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Title: Viral load, CD4 cell counts and antibodies:


1
Viral load, CD4 cell counts and antibodies What
do we know and what does it all mean? Brian
Williams, SACEMA, November 2007
2
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.
3
The standard model
Viral load
CD4
Time
Time
Acute phase weeks Final phase
months Interested in the long chronic phase 10
yrs
Antibodies
Time
4
Viral load and CD4 cell counts
Virions/mL
CD4 cells/mL
Orange Farm, South Africa. (Auvert et al. PLOS
Medicine, 2005)
5
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)
6
CD4 cell count decline for different viral loads
Rodriguez et al. Jama, 2006.
7
Antibody concentration and CD4 cell counts
? Up to 2000
CD4 cells /mL
Optical density ? log(antibody concentration)
ZVITAMBO (Hargrove, pers. comm.)
8
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
9
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)
10
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)
11
Log antibody distribution Harare
Frequency
Optical density i.e. ln(antibody concentration)
12
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
13
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
14
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)
15
Distribution of CD4 cell count decline
16
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)
17
So we need to explain why
18
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
19
Prevalence
Lusaka
Incidence
Gauteng
Death
00
00
05
10
40
05
95
95
10
90
90
40
20
Lusaka
Gauteng
21
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22
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