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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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Viral load cd4 cell counts and antibodies what do we know and what does it all mean

Viral load, CD4 cell counts and antibodies:

What do we know and what does it all mean?

Brian Williams, SACEMA, November 2007


Viral load cd4 cell counts and antibodies what do we know and what does it all mean

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.


Viral load cd4 cell counts and antibodies what do we know and what does it all mean

The standard model

Viral load

CD4

Time

Time

Acute phase ~ weeks

Final phase ~ months

Interested in the long chronic phase ~ 10 yrs

Antibodies

Time


Viral load cd4 cell counts and antibodies what do we know and what does it all mean

Viral load and CD4 cell counts

Virions/mL

CD4 cells/mL

Orange Farm, South Africa. (Auvert et al. PLOS Medicine, 2005)


Viral load cd4 cell counts and antibodies what do we know and what does it all mean

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)


Viral load cd4 cell counts and antibodies what do we know and what does it all mean

150

100

50

0

-50

-100

-150

-200

-250

-300

CD4 slope/mL/year

0.001 0.01 0.1 1 10 100 1000

Virions/μL

CD4 cell count decline for different viral loads

Rodriguez et al. Jama, 2006.


Viral load cd4 cell counts and antibodies what do we know and what does it all mean

Antibody concentration and CD4 cell counts

 Up to 2000

CD4 cells /mL

Optical density log(antibody concentration)

ZVITAMBO (Hargrove, pers. comm.)


Viral load cd4 cell counts and antibodies what do we know and what does it all mean

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


Viral load cd4 cell counts and antibodies what do we know and what does it all mean

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)


Viral load cd4 cell counts and antibodies what do we know and what does it all mean

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)


Viral load cd4 cell counts and antibodies what do we know and what does it all mean

Log antibody distribution: Harare

Frequency

Optical density i.e. ln(antibody concentration)


Combine the individual decline with the initial distribution

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


Viral load cd4 cell counts and antibodies what do we know and what does it all mean

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


Viral load cd4 cell counts and antibodies what do we know and what does it all mean

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)


Viral load cd4 cell counts and antibodies what do we know and what does it all mean

Distribution of CD4 cell count decline


Viral load cd4 cell counts and antibodies what do we know and what does it all mean

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)


Viral load cd4 cell counts and antibodies what do we know and what does it all mean

1. Survival is (almost) independent of initial CD4 cell count

2. Survival is (entirely) determined by log(set-point viral load)

3. Viral load declines exponentially with CD4:

4. Antibody concentration declines exponentially with CD4:

So we need to explain why:


Viral load cd4 cell counts and antibodies what do we know and what does it all mean

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 2001:355 11311137


Viral load cd4 cell counts and antibodies what do we know and what does it all mean

Prevalence

Lusaka

Incidence

Gauteng

Death

00

00

05

10

40

05

95

95

10

90

90

40


Viral load cd4 cell counts and antibodies what do we know and what does it all mean

Lusaka

Gauteng


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