Is Your HIV Treatment Working? Warning Signs and False Alarms

The first few months after you start HIV treatment are key in determining whether your first regimen will be successful—not just in the short term, but for years to come. But if you’re brand new to HIV treatment, how are you supposed you know what success really looks like?

Or, on the flip side, how can you tell if your HIV meds aren’t working as well as they should? It can be hard to tell the difference between a warning sign that your regimen might not be right for you and a normal signal that your body is still adjusting to treatment.

First and foremost, it's important to know that if your HIV medications (a.k.a. antiretrovirals) are chosen with thought and care (in which you work with an HIV care provider to understand treatment guidelines, watch out for any pre-existing HIV drug resistance, and account for underlying health issues such as liver, kidney or heart risks), and if you're able to be adherent to those medications (the goal is taking more than 90% of your pills), then HIV treatment almost always works at completely suppressing the virus, making your viral load undetectable in lab tests. It’s not a cure, but it is a lifesaver.

Treatment failure and HIV drug resistance, which were common in the 1990s and 2000s, are now exceptionally rare in people who take their medications. Side effects with today's medications are uncommon and usually mild. HIV meds can protect your health from developing AIDS, serious infections and cancers. And with an undetectable HIV viral load, you won't transmit the virus to others.

No one wants to take medications that could make them feel worse than before. It also can seem pointless to take a medication every day that isn't working right. It helps to pay close attention, communicate with your health care team, and be a part of every decision.

How do you really know if your HIV treatment is working? There are three key things to keep track of:

• How much your viral load is dropping.
• How much your immune system is recovering.
• How you're actually feeling.

How Do I Know If My Viral Load Is Dropping Enough After Starting HIV Treatment?

The goal of HIV treatment is to disrupt the replication of the virus so much that the amount circulating in your blood is extremely low. So low, in fact, that the blood test you'll take to keep track of your HIV—your HIV viral load—will report it as "undetectable." No matter how high your viral load is when you start treatment, "undetectable" is where you want to get to.

How long it takes to reach an undetectable viral load is very much influenced by how high your viral load is at the start. While more virus for HIV medications to attack often means more time to become undetectable, if you're adherent to your meds, your viral load should be undetectable within six months of starting treatment, and often much sooner.

This can also depend on the types of HIV drugs you’ve been prescribed: For instance, treatment regimens that include a family of HIV drugs called integrase inhibitors tend to cause more rapid declines in viral load than other families of medicines. But all of the HIV drug regimens commonly prescribed in the U.S. today are very good at getting viral load to undetectable.

It's unlikely your health care provider will start checking your viral load until you've been on your medications for at least a few weeks. According to U.S. treatment guidelines, viral load should be checked around two to eight weeks after starting treatment, and then every three to four months thereafter.

Although checking your viral load earlier after starting treatment may give you a sense of the pace of your viral load drop, it's getting to undetectable that really matters, and that can take time.

For people who are adhering well to treatment and have a consistently suppressed viral load for more than two years, viral load monitoring can be done at six-month intervals.

There Can Be Slightly Different Definitions of “Undetectable” HIV Viral Load

One of the things that can make conversations about viral load tests confusing is that “undetectable” doesn't always mean the same thing. Different clinics use different tests analyzed by different laboratories, and each lab may have a different cut-off point for measuring HIV in a sample of blood.

So, if your lab test has 50 copies/mL (that’s copies per milliliter, the standard measurement of HIV in the bloodstream) as the lowest detectable amount, but your friend's lab test detects viral loads as low as 20 copies/mL, what does it mean if your friend has detectable virus and you do not?

Obviously, less is better when it comes to HIV viral load. But we don't know precisely the significance of, let's say, 50 copies/mL versus 20 copies/mL. Measuring such tiny amounts of HIV in the blood is still a tricky business, and there is even some question about how reliable the measures are: If you were to repeat a viral load test, even with the same sample of blood in the same lab, the result would not necessarily be exactly the same.

One thing we do know with certainty is that regardless of how different tests may define “undetectable,” all of those definitions mean that your viral load is so low you cannot pass HIV on to another person through condomless sex. We call this “treatment as prevention” or “undetectable equals untransmittable” (U=U).

The Mystery of HIV Viral Load Blips

Even if you achieve a fully suppressed viral load and stay undetectable for months or years, it is possible that you will experience a small, temporary rebound to a viral load that's detectable but still very low (i.e., below 400 copies/mL). This is called a viral load blip.

There can be a variety of reasons for a blip (including lab variability or error), not all of which we completely understand. However, it’s important to know that a blip does not in any way mean your treatment regimen has failed or that you’re suddenly facing a health emergency.

Repeat testing will tell the story. If future tests show a three-fold increase or more in the amount of virus, then you and your provider may want to talk about your adherence to meds, additional monitoring tests (such as viral drug resistance tests) and, perhaps, switching to a different regimen.

The Bottom Line on First-Line HIV Treatment and Viral Load

Let's say you've been on your medications for several months, and what had been a consistent decline in your viral load has leveled out without reaching an undetectable level—or, worse, your viral load is going back up.

If this happens, you and your provider will want to figure out and address what might be slowing your treatment progress, and decide whether you need to switch regimens. The longer you stay on a combination that isn't fully suppressing the virus, the more risk there is of the virus becoming resistant to those medications, as well as other HIV medications you haven't even taken yet (called cross-resistance).

But when you're just starting out, as long as your viral load is generally moving toward undetectable, you're in good shape.

How Do I Know if My Immune System Is Recovering Enough After Starting HIV Treatment?

HIV infects and kills an important part of our immune system called CD4 cells. As we just discussed, an effective antiretroviral regimen should stop HIV from replicating and hurting your immune system. That gives your immune cells a break from HIV, allowing your body to stay healthy (if your CD4 levels were within the normal range when you started treatment) or recover (if your CD4 levels were low).

When it comes to measuring immune recovery, the conversation revolves around two major laboratory markers: your absolute CD4 cell count and your CD4 percentage, or the proportion of your white blood cells that are CD4 cells.

Depending on the person, the pace of a rise in CD4 cells after starting HIV treatment can be amazingly fast, frustratingly slow, or somewhere in between. People who begin treatment at a low CD4 cell count (below 200) often have a steeper hill to climb—and depending on how weak their immune system is to begin with, it may take longer to climb it. Other people might see a rise and then a leveling out, then see another rise after a long time on treatment.

The main measure of your health, of course, is whether you get sick any more often (or with more severity) than an HIV-negative person. But we can use CD4 count and CD4 percentage as ways to gauge the likelihood that you'll develop illnesses in the future.

U.S. HIV treatment guidelines recommend that a person’s CD4 levels get rechecked three months after starting medications, and then monitored every three to six months afterward until it reaches a steady state.

CD4 Count Can Be a Tricky Measuring Tool for HIV Treatment Success

The problem with obsessing about your CD4 cell count is that it can mislead you. Getting over a cold? Stressed out? Recently vaccinated against another disease? Getting your blood drawn at a different time of day than usual? Any of these things (and more) can influence the CD4 numbers you'll get back from the lab.

This is why knowing the percentage of white blood cells that are CD4 cells can be more useful: It can help distinguish a real change from one that looks like a big deal but isn't.

CD4 numbers can fluctuate a lot, even in healthy people. Your CD4 percentage is less variable than your CD4 count because, if your absolute number of CD4 cells is down, it's sometimes because your larger pool of white blood cells is also down. A significant change in CD4 is considered a 30% change in your absolute count or a 3% change in your CD4 percentage.

On top of all this, it’s hard to set a specific CD4 number or percentage as a goal for HIV treatment because everybody’s normal range is different. A normal CD4 count for an HIV-negative person can be anywhere between 500 and 1,500, and a normal CD4 percentage can vary from 30% to 60%.

While it's understandable why people might worry about their lab numbers, if your viral load is suppressed and CD4 values have been somewhere within the normal range for more than two years, and as long as you stay adherent to treatment, you no longer need to worry about the numbers. In fact, U.S. treatment guidelines say that if your CD4 count remains normal for a couple of years and your viral load is also undetectable, it’s optional whether you continue to get your CD4 levels retested at all, because your immune system is healthy.

The Bottom Line on First-Line HIV Treatment and CD4 Count

HIV treatments work to allow your immune system to recover and remain health. You likely don't know what your normal CD4 count was before you acquired HIV, and everyone is different; but in general, having more CD4 cells and a higher CD4 percentage are a good thing.

Talk to your health care provider about what your test results mean. If you've maintained viral suppression and your CD4 numbers are in the normal range, you can take a deep breath and relax—you might even not need to worry about CD4s at all in the future. If your counts remain low, be patient: Some people do take longer to recover than others, and the amount of CD4 gain a person experiences doesn’t appear to be related to the specific HIV meds they’re on.

How Can I Assess How Well My HIV Treatment Is Working Based on How I’m Feeling?

There are few certainties in HIV treatment, but one is that you can't tell what your viral load or CD4 count is by how you feel. Only those blood tests you take can tell you for sure. However, focusing on how you feel can give you a lot of important information about how your HIV medications are working for you.

Every medication in the world has potential side effects and toxicities. Some meds are more likely to cause side effects than others, and some may be more likely in some people than others. It's important to take note of changes in the way you feel after you start treatment and beyond—both physically and mentally.

HIV Medication Side Effects Are Most Common in the First Few Weeks

With today's medications, most people don't notice much of anything when they start treatment. Others have a minor side effect or two (like headaches, nausea, or diarrhea) that will dissipate over the first few weeks. Still others have severe side effects that can make daily life harder or become a health risk; they may go away after a few weeks, or (rarely) they may persist.

If you get a new symptom after starting treatment that becomes worse or doesn't go away, it's important to bring it to your HIV care provider’s attention quickly. There might be blood tests to run or further discussions you can have that will help determine whether it’s definitely the HIV meds causing the problem, and what you can do about it.

If the symptoms are related to one of your medications, switching to a different medication will likely alleviate the side effect and any health risks.

If You Started HIV Treatment With a Low CD4 Count, Watch Out for IRIS

People who start treatment at a low CD4 count (below 200) might suddenly experience a whole array of confusing and frightening symptoms: fever, swollen lymph nodes, congested breathing—the sorts of symptoms that you might feel if your body were reacting to a bad bacterial or viral infection.

In fact, that's likely exactly what's happening: What you're experiencing may well be Immune Reconstitution Inflammatory Syndrome (IRIS). Believe it or not, IRIS is a sign that the medications you're taking are helping the immune system—and, as a result, your body is now able to recognize and mount a response to invaders that have been taking advantage of your weakened state.

Although IRIS might make you feel worse at first, once your recovering immune system fights off the infection, you'll usually start to feel much, much better than before you started treatment. This is why it’s usually important to continue taking HIV meds even if you’re going through IRIS.

However, if you develop symptoms of IRIS, it also means your HIV care provider should be involved. This is because extreme cases of IRIS can cause you to get very sick and sometimes require hospitalization, so it’s important for your clinician to provide close monitoring and support until you recover.

Watching the Horizon: HIV Meds Beyond the First Few Months

After a while on treatment, you might find that you're experiencing a side effect you didn't notice before or that bothers you now more than it used to. For instance, maybe you started HIV meds and discovered over the course of several months that your sleep isn't that great, or your mood has slipped.

While today's medications are vastly better tolerated than those in the past, there are still unanswered questions about the long-term effects of HIV medications. We know that they can allow a person to live just as long as someone who’s HIV negative, but we’re still learning about how HIV (even when fully suppressed) or the meds keeping HIV at bay can affect the health issues a person experiences over their lifetime.

Be sure to stay in touch with your health care team about some of these potential long-term health issues. And stay educated about side effects and other problems that people with HIV tend to experience as they grow older.

The Bottom Line on Side Effects of First-Line HIV Treatment

If you find yourself not feeling well days, weeks, or months after you've started HIV treatment—particularly if that feeling isn't going away or is getting worse—you may find yourself facing a challenging question: "Do I want to try to find ways to manage this symptom, because my regimen is working and I'm able to keep up with my doses? Or do I want to see what a new regimen has to offer, both good and bad?"

If you find yourself in this place, know that you have the power to answer it. This is a very personal decision, one best made thoughtfully and carefully after discussion with your health care providers.

It can be nerve-wracking to start an antiretroviral regimen. Fortunately, the fear of what might happen is usually worse than what actually happens. In fact, the vast majority of people feel better after they start HIV treatment. They feel better physically, because the medications are stopping the unchecked replication of HIV in their bodies and helping their immune systems to recover. And they feel better emotionally, for a whole host of potential reasons—possibly including better physical health, knowing their HIV is under control, feeling confident they can’t transmit HIV to others, and generally beating a lot of their fears and anxieties about HIV treatment.

Still, the key for anybody beginning HIV treatment is to be aware of these key ways to measure success, know how to spot potential warning signs, educate yourself about their causes and solutions, and talk openly with your health care providers about your concerns and options. Doing so will help ensure that your treatment remains on track no matter what obstacles pop up.

[Editor's note: Although Ben Young, M.D., Ph.D., co-authored this article when it was first published in 2017 and maintains his byline in accordance with our editorial guidelines, he did not co-author a major update to this article in 2020.]