What Is a CD4 Count and Viral Load?

Measuring Your Immune Status and HIV "Viral Burden"

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Jim Gathany/Centers of Disease Control and Prevention (CDC)

If an HIV infection has been confirmed, tests are routinely performed to determine the status of a person's immune system and the level of viral activity in the body. These are expressed in what is known as your CD4 count and viral load.

What Is a CD4 Count?

The CD4 test is one of the more familiar testing assays known to people with HIV. The test measures the level of CD4 helper T-cells in the blood—cells that are not only vital to immune function but are the primary target of HIV infection.

As HIV gradually depletes these cells, the body becomes less able to defend itself against a widening range of opportunistic infections.

The test is performed by taking a blood sample, the results of which measure the number of CD4 cells in a microliter (µL) of blood. The baseline count establishes the status of your immune system, while follow-up testing largely informs us about

  • the stage of infection and rate of disease progression
  • the likelihood that certain infections will develop as CD4 cells are depleted
  • how well you are responding to treatment either by maintaining or reconstituting your immune function

Normal CD4 counts are anywhere between 500-1,500 cells/ µL. Conversely, a CD4 count of 200 cells/ µL or less is technically classified as AIDS. Research has shown that initiating therapy at or below this level correlates to poorer clinical outcomes and the reduction in life expectancy by as much as 15 years.

Previous treatment guidelines recommended that antiretroviral therapy (ART) be initiated in patients with a CD4 count under 500 cells/µL or in the presence of an AIDS-defining illness. In 2016, updated guidelines endorsed ART in all HIV-infected patients, irrespective of CD4 count, location, income, or stage of disease.

Today, the CD4 count is used to predict disease outcome as much as to measure an individual's relative immune strength. By way of example, the CD4 nadir (the lowest point to which the CD4 count has dropped) is predictive of long-term morbidity, with lower values suggesting an increased risk of HIV-related and non-HIV-related illnesses, as well as slower immune recovery.

What Is a Viral Load?

While the CD4 count is an indicator of immune status and treatment efficacy, the viral load is arguably the more important measure when antiretroviral therapy begins.

The viral load measures the concentration of virus in the blood, also known as your "viral burden." Labs will use a genetic testing technology—typically, the polymerase chain reaction (PCR) or a bDNA (branched DNA)—to quantify the number of viral particles in a milliliter (mL) of blood. HIV viral loads can range from undetectable (below the detection levels of current testing assays) to the tens of millions.

An undetectable result does not mean there is no virus in your blood or you have been "cleared" of infection.

(In fact, less than 5% of HIV in the body can be found in the blood.) Undetectable simply means that the virus population has fallen below testing detection levels in blood but may be detectable elsewhere, such as in the semen.

Goals of Viral Suppression

The aim of antiretroviral therapy is to fully suppress viral activity to undetectable levels, which, in turn, is associated with

  • greater treatment durability
  • a lower risk for the development of drug resistant virus
  • better clinical outcomes correlating to increased life expectancy,
  • the reduction of HIV transmission risk to an uninfected sexual partner (a strategy popularly referred to as treatment as prevention (TasP)).

On the other hand, an increase in the viral load can often be an indication of treatment failure, poor drug adherence, or both.

It's important to note that drug adherence of at least 95% is required to ensure viral suppression to undetectable levels. Uneven adherence not only reduces a person's ability to achieve this, it increases the likelihood of treatment failure by allowing drug resistant virus to develop. This cause-effect relationship is the reason adherence should always be checked before therapy is changed.

That said, incidental variations in viral load (or "blips") can occur even among those with 100% adherence. These are usually minimal and should not be the cause for alarm.

Regular monitoring of the CD4 count and viral load is recommended, usually every three to six months after which the CD4 can be checked every 6 or 12 months if between 350 and 500 cells/µL. Patients able to sustain CD4 counts over 500 cells/µL may be tested occasionally as directed by treating doctor.

Benefits of Viral Control

According to research from the U.K. Collaborative Cohort Study (UK CHIC), people with undetectable viral loads who achieved a CD4 count of 350 cells/µL or more within a year of starting therapy were likely to have a normal life expectancy.

On the flip side, failure to achieve viral suppression reduced life expectancy by as much as 11 years—equivalent to smoking 40 cigarettes per day.

A retrospective analysis conducted in 2013 by the University of Montreal further concluded that persons who had "near undetectable" viral loads for a period of six month (i.e., between 50 and 199 copies/mL) had nearly a 400% greater risk of virologic failure within a year than those able to achieve complete viral suppression.

The study, which monitored 1,357 HIV-positive men from 1999 to 2011, further demonstrated a virologic failure rate of nearly 60% in persons with persistent viral loads of between 500 and 999 copies/mL.

Sources:

U.S. Department of Health and Human Services (DHHS). "Guidelines for Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents." AIDSinfo Update. Rockland, MD; February 12, 2013: C9-C21.

May, M.; Gompels, M.; and Sabin. C. "Life expectancy of HIV-1-positive individuals approaches normal conditional on response to antiretroviral therapy: UK Collaborative HIV Cohort Study." Journal of the International AIDS Society. November 11, 2012; 15(4): 18078.

Baligh, Y.; Fleishman, J.; Metlay, J.; et al. "Sustained Viral Suppression in HIV-Infected Patients Receiving Antiretroviral Therapy." The Journal of the American Medical Association. July 25, 2012; 308(4):339-342.

Laprise, C.; de Pokomandy, A.; Baril, J.; et al. "Virologic failure following persistent low-level viremia in a cohort of HIV-positive patients: results from 12 years of observation." Clinical Infectious Diseases. November 2013; 57(10):1489-96.

The INSIGHT START Study Group."Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection."New England Journal of Medicine.July 20, 2015; DOI: 10.1056/NEJMoa1506816.

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