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A Pharmacist Shows You the Journey to "Undetectable"

November 21, 2013

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When a person living with HIV, together with his or her clinician, decides it is the right time to start antiretroviral therapy (ART), one major goal is usually to "get to undetectable" -- that is, to suppress viral replication so that very low levels of virus remain.

And today, that goal is more attainable than ever. "With the currently available potent HIV regimens, I don't see why we can't achieve close to 100% of patients reaching undetectable viral loads," says Chris Nguyen, an HIV pharmacist with Walgreens in San Francisco.

Read on to understand how undetectable viral load is reached, and for tried-and-true strategies and tips for keeping the virus in check.


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Measuring the Descent

The journey to undetectable is similar to climbing down a steep mountainside to safer ground. Viral load is like a marker of your descent down the mountain, and antiretroviral therapy (ART) can be seen as a rope you use to climb down safely.

Within six weeks of starting ART, your clinician is looking for a sharp drop in your viral load, usually a 1-log drop. (Click here for a handy cheat sheet on "log" changes.) For example, on the logarithmic scale, a viral load of 100,000 copies/mL is equal to 5 log copies/mL. After six weeks, your clinician might check to see whether the viral load has decreased to approximately 4 log copies/mL (10,000 copies/mL), which represents a 1-log reduction. After 24 weeks, highly effective ART should result in an undetectable viral load.

Some people mistakenly think that being "undetectable" means that there is no HIV virus left in the body. This is not the case. "Undetectable" means that there is such a small quantity of virus circulating in the blood that none was seen in a particular blood sample.

One of two assays, either reverse transcriptase polymerase chain reaction (RT-PCR) or branched DNA (bDNA), is typically used to measure the amount of HIV-RNA (HIV's genetic material), in a small sample of blood. Each assay gives a good estimate of the burden of virus in the body, but lab machinery is never perfect, and both the RT-PCR and bDNA have upper and lower limits to how well they represent virus levels. In addition, some cells contain dormant HIV that is not currently replicating but has the potential to do so. These cells make up the "latent HIV reservoir," and RT-PCR and bDNA assays cannot measure the amount of virus they contain.

For these reasons, when you have an undetectable viral load, your count is not listed as "zero"; it may instead be listed as <75 copies/mL (for a bDNA test) or <20 copies/mL (for the most sensitive RT-PCR). There is some variation between the standard tests used to monitor viral load; clinicians typically aim for the ART regimen to suppress the virus to below 50 copies/mL.

Why do clinicians strive for undetectable? "Keeping an undetectable viral load allows your immune system to begin its recovery and means the virus will not develop resistance to your meds," says Dr. Ruth Greenblatt, a physician at San Francisco General Hospital with more than 20 years of experience caring for people living with HIV and AIDS.


What It Takes

Like climbing down a mountain, getting to undetectable takes some work, but it is possible with the right equipment. Suppressing HIV to undetectable levels depends on finding the right regimen -- and sticking to it -- to stop the virus from hijacking more of the body's cells and making new copies of itself.

Adhering to an ART regimen is one of the foundations of HIV treatment, and it can take some getting used to. (See below for some strategies to boost adherence.) But today, as Dr. Nguyen points out, "many of the regimens are very well tolerated, which helps." And the rewards are huge: "I remember one of my newly diagnosed patients coming in a month after starting his regimen, raving about how his viral load has drastically dropped in such a short amount of time, and how happy his provider was," Dr. Nguyen recalls. "It brought a big grin to my face seeing how excited he was."

Good adherence involves taking the right pills at the right time on a regular basis, to keep drug levels high enough to continually suppress HIV replication. When you interrupt your ART or miss doses, the levels of those HIV-fighting drugs decline -- sometimes imperceptibly, sometimes quit a bit. When drug levels decline too far to keep the virus in check, HIV can resume replicating, and viral load rises.


The Adherence-Resistance-Viral Load Connection

Closely connected to low adherence is the possibility of drug resistance. To keep HIV in check, an ART regimen must include drugs from multiple drug classes that block replication at different stages in the viral lifecycle. When missed doses cause drug levels of one or more medications to fall and the virus replicates, the new copies may contain genetic mutations against those drugs, rendering them less effective or even ineffective and limiting future options for treatment.

Scientists and clinicians know that low adherence can lead to HIV drug resistance, but they are still trying to better understand the specifics. For example, many people living with HIV have long been advised to take at least 95% of their medicines each month. It is certainly true that adhering your regimen at least 95% of the time can help avoid resistance and keep your viral load undetectable. However, researchers are currently exploring whether lower levels of ART adherence may be possible without sacrificing viral suppression.

Dr. David Bangsberg's studies in the San Francisco-based REACH cohort found that a group of people on non-nucleoside reverse transcriptase inhibitor (NNRTI) regimens still had an undetectable viral load even though they were skipping 25%-50% of their doses. Other researchers are also beginning to recognize that different patterns of adherence (such as skipping on the weekends versus skipping more sporadically) may have different impacts on resistance and viral load. And another study found that participants who had been undetectable for twelve months prior to skipping doses had a 47% lower risk of virologic failure (that is, failure of the drugs to keep the virus suppressed) compared with those who had been undetectable for only one month before reducing their adherence.

That said, the jury is still out on the long-term effects of "drug holidays" and low adherence. Conducting these types of studies helps scientists, clinicians, and people living with HIV learn about patterns of adherence that may be harmful, and what effect the occasional missed dose might have. We have not yet learned enough to translate these studies into practice, so taking ART consistently is still the best way to keep the virus undetectable.

If you find yourself skipping doses (or wanting to skip them), have an open conversation with your clinician about it. She or he may be able to guide your adherence strategies, discuss simpler regimens, and/or address any side effects or other issues that you may be finding a challenge.

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This article was provided by BETA. Visit their website at www.betablog.org.
 
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