Monitoring the immune system

Derek Thaczuk

HIV infection gradually causes changes in the human body. The level at which the immune system is functioning can be monitored with several blood tests that provide insight into both how well someone's immune system is fighting the virus and the type and amount of virus present.

The CD4 cell count measures immune function. Another common test, the viral load test (measuring HIV's RNA), provides a direct measure of the amount of HIV circulating in the blood. Both of these tests are considered independent markers of HIV disease progression.1

A viral load test and CD4 cell count together can:

  • Evaluate current immune system status.
  • Guide and monitor treatment decisions.
  • Predict rate of disease progression in the short- and the long-term.

CD4 cells counts, viral load tests, and resistance testing provide information about the effects of HIV disease on an individual that can then be interpreted in the context of what is known about the natural history, or normal course, of HIV disease and AIDS.

What is not quantified is the role and extent of immune activation (host response) and the effect that may have on T-cell turnover and CD4 cell depletion. HIV continuously evolves after primary infection, adapting to the pressure the immune system exerts on it. The balance between this pressure and the success of the virus in adapting to it determines the rate of disease progression. Clinically, this is reflected by the level of viral load and CD4 cell count, while within the virus, genetic changes become apparent.

Viral load tests and CD4 cell counts are used to inform treatment decisions. A person may be advised to start antiretroviral therapy (ART) when the CD4 cell count declines below a certain level. The decision to start prophylaxis against certain infections is often based on the CD4 cell count, as the risk of developing certain infections is directly related to it. In places where CD4 testing is not readily available or affordable, prophylaxis may be offered based on clinical impression and/or a pathogen's prevalence in a particular setting. In some places, the use of ART is not authorised and/or its cost reimbursed by insurance until the CD4 count falls below a certain level.

The decision to start ART is often made when a person has detectable viral load. A viral load decrease within the first few weeks of starting an ART regimen is generally a positive predictor of regimen success over time. Subsequent viral load increases on two consecutive occasions may indicate a need to change the regimen or to take a closer look at adherence. Even a single viral load measurement is highly predictive of time to AIDS, but a series of measurements over time better predicts disease progression.2 1 3 4

Resistance testing can provide information on drugs that a particular HIV virus may be sensitive or resistant to (phenotypic testing) and on mutations in the genetic code of the virus (genotypic testing) that would affect treatment choices.

Tropism testing is generally recommended before using a drug from the CCR5 inhibitor class of antiretrovirals. Untreated patients infected with X4- or dual/mixed-tropic virus generally experience a significantly greater decrease in CD4 cell count over 12 months with more clinical events than patients with R5-tropic virus. For these reasons, it might be helpful to determine tropism as a guide in making clinical decisions as to the frequency of monitoring and timing of starting ART; however, there are insufficient data at present to support using tropism testing for prognostic purposes.

Once ART is started, patients seem to experience comparable increases in CD4 cell count and an ability to achieve an undetectable viral load, regardless of tropism.5 See Receptors, co-receptors and immunity to HIV for further information.


  1. Lau B et al. Predictive value of plasma HIV RNA levels for rate of CD4 decline and clinical disease progression. Fourteenth Conference on Retroviruses and Opportunistic Infections (CROI), San Diego, abstract 140, 2007
  2. Mellors J et al. Comparison of plasma HIV-1 RNA, CD4 cell count, and CD38 expression on CD8 T cells as predictors of progression to AIDS and CD4 cell decline among untreated participants in the Multicenter AIDS Cohort Study. Fourteenth Conference of Retroviruses and Opportunistic Infections, San Diego, abstract 139, 2007
  3. Mellors JW et al. Prognostic value of HIV-1 RNA, CD4 cell count, and CD4 cell count slope for progression to AIDS and death in untreated HIV-1 infection. JAMA 297(21): 2349-2350, 2007
  4. Rodriguez B et al. Predictive value of plasma HIV RNA level on rate of CD4 T-cell decline in untreated HIV infection. JAMA 296 (12): 1498-1506, 2006
  5. Waters L et al. The impact of HIV tropism on decreases in CD4 cell count, clinical progression, and subsequent response to first antiretroviral therapy regimen. Clin Infect Dis 46: 1617-1623, 2008
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We can end HIV soon if people have equal access to HIV drugs as treatment and as PrEP, and have free choice over whether to take them.

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