Why Can't I Get My CD4 Count Up?

Factors for CD4 Recovery Remain Highly Variable in People on HIV Therapy

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The CD4 count is defined, most simply, as the means by which to measure the strength of the immune system of a person with HIV. It is a test used both to monitor the progression of HIV infection and to predict the likely outcome (prognosis) of a disease.

Understanding the CD4 Count

Among the components of the immune response are specialized white blood cells known as CD4 T-cells, whose main purpose is to sound the alert when disease-causing pathogens like HIV are present.

Ironically, they are also the same cells predominately targeted for infection by HIV. Over time, if left untreated, HIV will gradually deplete these cells, leaving the immune system effectively blind and progressively unable to defend itself.

The CD4 count can range anywhere from what would be consider normal in an uninfected person (800-1500 cells/mL) to where a person's immune system is considered compromised (under 200 cells/mL). As the number drops even further to below 100 cells/mL, the risk of a major opportunistic infection increases exponentially.

One of the goals of antiretroviral therapy (ART) is to restore  the immune strength of an HIV-infected individual. By preventing the virus from actively replicating, ART helps the body mount its own recovery, reconstituting the CD4 population, ideally to normal levels.

But, the truth is, that doesn't always happen.

In some cases, failure to reconstitute immune function is a direct result of suboptimal drug adherence, including inconsistent and/or incorrect dosing.

If viral activity is allowed to persist and the HIV viral load is not fully undetectable, CD4 cells can continue to be depleted, undermining the very goals of therapy.

But what if a person is fully adherent and still not able to get their CD4 count up? Does that mean the drugs are not working? Is this an indication that treatment should be changed?

More often than not, the answer is no.

Barriers to CD4 T-cell Recovery

Ultimately, the aim of ART is to suppress viral activity—to reduce the viral load to where there is no virus detected in the blood. That is the direct action of the drug and something that is generally achievable in people who remain adherent to therapy.

By contrast, T-cell restoration is more the effect of viral suppression than of ART itself. The drugs have no direct action on the CD4 count other than to remove the viruses that are killing the T-cells off.  That means that recovery can differ dramatically from person to person, with some bouncing back immediately and fully, while others stabilize at far lower levels over the long term.

One the primary causes for this effect is the CD4 nadir. The nadir is simply is the lowest point that the CD4 count has dropped before intervention is made. The CD4 nadir is not only able to predict the likelihood of certain illnesses, such as HIV-associated brain disorders, it can oftentimes predict the robustness of a person's immune recovery after therapy begins.

Generally speaking, people with a very low CD4 nadir (under 100 cells/mL) will have a far more difficult time restoring immune function than a person with, say, moderate immune suppression (over 350 cells/mL).

It 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 greater improved, as is the likelihood of achieving a normal, healthy life expectancy.

HIV and T-cell Exhaustion

By the time that a CD4 count has dropped to below 100 cells/mL, the immune system will have been exposed to years and even decades of damage, both in terms of the persistent inflammation caused by HIV infection and the direct injury of tissues and cells by the virus itself.

It is during this time that an effect called T-cell exhaustion can occur. T-cells exhaustion is one of the consequences of severe or long-term infection, wherein the very 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—considered "killer" cells to CD4's "helper" cells—we now know that CD4 T-cells can also be adversely affected.

What Can I Do to Improve My CD4 Count?

The factors for the restoration of immune function in people with HIV are numerous and varied. There is not a single approach one can take other than to remain adherent to ART and to sustain undetectable viral loads.

There are no compounds or agents (including nutritional supplements, holistic medications, vitamins, or so-called "immune boosters") that have an associative impact on CD4 T-cell reconstitution. Despite suggestions to the otherwise, no study has ever linked any such oral or injectable agent to improvements in CD4 counts.

With that being said, positive lifestyle choices can have a significant on an person's health outcomes, whether HIV-infected or not. Appropriate exercise, a healthy diet, smoking cessation, and a reduction in alcohol intake all offer strong returns to people with HIV, even if an individual's CD4 count hovers well below normal levels.

If you are adherent to therapy and have an elevated viral load—even persistent, low-level activity—speak with your doctor. It may suggest that you're developing HIV drug resistance. In such cases, treatment may need to be changed.

However, individuals with a fully suppressed virus and stagnating CD4 counts should not change ART based on the assumption that it will improved CD4 outcomes. Change should only be made in the event of treatment failure or as a result of adverse treatment effects.

Sources:

Negredo, E.; Massanella, M.; Puig, J.; et al. "Nadir CD4 T Cell Count as Predictor and High CD4 T Cell Intrinsic Apoptosis as Final Mechanism of Poor CD4 T Cell Recovery in Virologically Suppressed HIV-Infected Patients: Clinical Implications." Clinical Infectious Diseases. 2010; 50(9):1300-1308.

Crawford, C.; Angelosanto, J.; Kao, C.; et al. "Molecular and Transcriptional Basis of CD4+ T Cell Dysfunction during Chronic Infection." Immunity. February 20, 2014; 40(2):289-302.

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