Barriers to Boosting CD4 Counts

Key Factors Affecting Immune Recovery

White blood cell flowing in the bloodstream with red blood cells.
Biogeek / Getty Images

A CD4 count is a measurement of the number of a particular type of white blood cells (lymphocytes), CD4 T-cells, that help fight infection. As such, it's an important indicator of the strength of the immune system for people with HIV. Regular testing to evaluate CD4 is used to monitor the progression of infection, to help predict the likely outcome (or prognosis) of the disease, and to evaluate how well treatment is working.

Improving a person's CD4 count is a key goal of antiretroviral therapy (ART), but even for those who are strictly compliant about taking their medication as prescribed, CD4 sometimes doesn’t improve.

A primary reason for this has to do with timing: The earlier ART is started, the more effective it's likely to be. If you've recently tested positive for HIV infection, you'll want to understand the importance of keeping tabs on your CD4 count and how beginning treatment as soon as possible can impact it.

Understanding the Numbers

When the immune system becomes activated by a virus such as HIV, part of the response includes the release of CD4 cells. Also known as helper cells, their role is to trigger the release of another type of T cells, CD8, or killer cells, that actually destroy the virus.

CD4 cells are the lymphocytes targeted by HIV. Without treatment, over time the virus will gradually deplete them, leaving the immune system unable to defend itself.

CD4 counts are expressed as number of cells per cubic millimeter (mL) of blood:

  • Normal: Between 500 and 1,200 cells/mL
  • Weakened immune system/possible HIV infection: Between 250 and 500 cells/mL
  • AIDS/high risk of life-threatening opportunistic infections: 200 or fewer cells/mL

Barriers to CD4 Recovery

A chief goal of antiretroviral therapy is to restore the immune strength of a person with HIV by preventing the virus from actively replicating. As long as ART is adhered to consistently, there generally will be an increase in the number CD4 cells detected in blood tests.

However, if this doesn't occur, a couple of factors largely having to do with the timing of the start of medication may be to blame.

CD Nadir

One of these is the CD nadir, which refers to the lowest level to which a person's CD4 count dropped before they began medication.

The CD4 nadir can help predict the likelihood of certain illnesses, such as HIV-associated brain disorders, as well as how robust the immune system will be after therapy has already begun.

In general, someone with a very low CD4 nadir (under 100 cells/mL) will have a more difficult time restoring immune function than a person with moderate immune suppression (over 350 cells/mL).

T-Cell Exhaustion

Another potential barrier to a robust CD4 count is a phenomenon called T-cell exhaustion. By the time a CD4 count has dropped to below 100 cells/mL, the immune system will have been exposed to years of damage from both persistent inflammation caused by HIV infection and direct injury to tissues and cells by the virus.

T-cell exhaustion is one of the consequences of severe or long-term infection. It means that the structure and genetic coding of the cells are altered at the molecular level. Over time, the T-cells lose their ability to function and prevent disease progression.

While T-cell exhaustion has been primarily associated with CD8 T-cells, CD4 T-cells can also be adversely affected.

Improving the CD4 Count

Although a host of factors go into restoring immune function that's been depleted by HIV, there's no single thing an infected person can do to boost CD4 levels aside from taking their ART medication as directed. No nutritional supplements, holistic medications, vitamins, or "immune boosters" have been found to support the reconstitution of CD4 T-cells.

Even so, positive lifestyle choices can have a significant impact on overall health. Regular exercise, a healthy diet, quitting smoking, and cutting alcohol consumption are all beneficial for people with HIV, even for those whose CD4 count hovers well below normal levels.

Routine testing of CD4 counts also is important:

  • For newly diagnosed people, CD4 testing should be performed prior to starting ART, repeated three months after therapy begins, and every three to six months thereafter.
  • For those who have been on ART for at least two years and have had sustained, undetectable viral loads, testing should take place every 12 months for those who have CD4 counts between 300 and 500 cells/mL.
  • For those with CD4 counts over 500 cells/mL, CD4 monitoring is optional.

If testing reveals an elevated viral load, or even persistent, low-level activity, it may indicate the development of HIV drug resistance. In such cases, treatment may need to be changed.

A Word From Verywell

There's no doubt a diagnosis of HIV infection is scary but thanks to our understanding of how the virus works and how it can be stopped from replicating, the majority of people who are HIV-positive do not go on to develop AIDS.

This is especially true the sooner the virus is detected and treatment begins, which is why ART is now recommended at the time of diagnosis for all people with HIV. By starting treatment earlier rather than later, the chance of a full immune recovery is improved, as is the likelihood of achieving a normal, healthy life expectancy.

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