Why Can't I Get My Viral Load Down?

5 Simple Questions May Help Identify the Problem

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An HIV viral load is simply the measure of the amount of virus in your blood. The goal of antiretroviral therapy (ART) is to reduce the number of HIV particles to so-called "undetectable" levels, meaning that the virus cannot be detected by current testing technologies.

Currently in the U.S., less than 70% of people on ART are able to achieve and sustain undetectable viral loads, and that's a problem.

Not only does it increase the risk of premature treatment failure, it can result in the development of resistance and cross-resistance to a person's HIV drugs—sometimes even an entire class of drugs.

If you are unable to achieve an undetectable viral load and are uncertain why, start by asking yourself a few simple questions:

Am I being as adherent to therapy as I could be?

There has long been a mantra in the HIV treating community that patients on ART need to achieve "at least 95% adherence" to their medication in order to achieve viral suppression. But what does this really mean?

Consider, for example, that 95% adherence means that a person on a once-daily drug regimen can theoretically miss up to 13 doses per year, or roughly one dose one dose per month. While that may seem understandable—people do make mistakes, after all—what if you look back and are not quite certain how many you've missed?

Could it have been more?

Are there situations or occasions (like business trips or days when you've been rushing the kids off to school) where you've traditionally missed doses or have found yourself catching up on a dose you've taken late? Oftentimes, these patterns add up over a course of a year and can impact your ability to achieve viral suppression.

Also consider that 12-hourly doses mean every 12 hours, not one dose at 6:00 am and the next at midnight.  While current-generation antiretrovirals are more "forgiving" than ever, with longer half-lives and durability, ensuring regularly spaced doses is always good practice as it helps maintain a consistent concentration of drugs in your bloodstream.

Have I had interruptions in treatment?

While missing the odd dose here or there is generally not a big deal, it becomes increasingly more concerning when doses are missed in succession. To some people, 95% adherence means that you're allowed to miss 5% of your doses, and therefore think nothing of interrupting treatment for two, three, even four doses at time.

It may be that it's a big party weekend, and the last thing you want to think about is HIV. Or it may be that you're occasionally depressed or burned out by the daily grind of taking pills.

The problem is that treatment interruptions like these are more likely to cause the premature development of drug resistance, particularly with earlier-generation drugs like Viramune (nevirapine) and Sustiva (efavirenz), among others.

If you have had treatment gaps, you need to be honest with yourself and your doctor. Don't worry about being a "good patient" and telling your doctor what he or she may want to hear. By working together, you can more often find the means to overcome adherence barriers, whether it be emotional, functional or therapeutic.

Do any of my medications have dietary restrictions?

A number of antiretroviral drugs have dietary requirements, such as Edurant (rilpilvirine) which not only requires a high-fat diet but is 40% less effective when taken without food. Others, like Prezista (darunavir), also require food intake while some, like Atripla (tenofovir + emtricitabine +efavirenz), is best taken on an empty stomach or before food is even eaten.

While this is generally a less common reason for elevated viral loads, it is possible that they can add to the problem. Check your dosing instructions and contact your doctor or health provider if you have any questions about food requirements with your HIV drugs.

Could drug interactions be the problem?

While this, again, is a less common cause for elevated viremia in patients on ART, some interactions can actually have a profound effect on HIV drug bioavailability (i.e., the amount of drug that ends up in your bloodstream after taking a pill).

One of the most common interactions is between the drug rifampin (rifampicin) used in the treatment of tuberculosis. Rifampin has significant interaction with many HIV drugs, with some like Sustiva (efavirenz) or Norvir (ritonavir) requiring higher doses in order to maintain adequate drug levels.

Even common, over-the-counter antacids (like Tums, Maalox, Mylanta or Milk of Magnesia) have significant impact on HIV drug bioavailability, requiring a separation of doses by anywhere from one to six hours. These include such antiretroviral agents as Tivicay (dolutegravir), Edurant (ripilvirine) and Stribild (tenofovir + emtricitabine + elvitegravir + cobicistat).

 If taking antacids regularly, speak with your doctor ensure you are doing so without ill effect to your HIV medications. For all other possible drug interactions, make sure your doctor is aware of any other drugs or supplements you may be taking—particularly if your prescriptions are not consolidated with a single pharmacy or drug provider.

Do I have HIV drug resistance?

HIV drug resistance develops in one of two ways: either as the virus mutates in presence of ART, with some mutations less able to resist the effects of the antiretroviral medication; or as a results of transmitted resistance, wherein a person with HIV resistance passes it on to another person.

In either case, drug resistance can be easily confirmed by way of an HIV genotyping, which identifies which types of genetic mutations an individual's virus may or may not have.

The problem occurs when these tests are not readily available, as often happens in resource-limited settings. In cases like these, doctors are often forced to make the call as to whether their patient's viral elevation is a result of developing drug resistance, poor adherence, or a combination of the both. Changing therapy early based on presumed resistance can be a big problem, particularly if adherence is an underlying (or unspoken) factor.

Doctors can often assess adherence by way of pharmacy records or by tracking the way in which the person's viral load is trending. Generally speaking, if drug resistance is developing, viral loads will trend upward over the course of several blood tests. If, on the other hand, it fluctuates wildly—with sudden spikes in viremia interspersed with undetectable viral loads—then one might rightly assume that drug adherence is an issue.

In terms of transmitted resistance, rates can be as high as 15-20% in high-income countries, while low- to middle-income countries hover closer to 7%.  So it does remain concern, particularly in countries where access to genotypic technologies is limited.

If you find your viral load creeping skyward or maintaining at levels higher than undetectable, contact your doctor and discuss whether you should motivate for a genotyping from your insurer or healthcare provider.   

Sources:

Centers for Disease Control and Prevention (CDC). "CDC Fact Sheet | HIV in the United States: The Stages of Care." Atlanta, Georgia; published July 2012.

University of Liverpool. "Food Considerations for Antiretrovirals." Liverpool, England; online publication; accessed October 4, 2015.

University of California, San Francisco. "Database of Antiretroviral Drug Interactions." San Francisco, California; online database; accessed October 4, 2015.

World Health Organization (WHO). "WHO HIV Drug Resistance Report 2012." Geneva, Switzerland; published 2012; ISBN 978 92 4 150393 8.

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