Atripla for HIV Treatment: Everything You Need to Know

Atripla Basics and History

Atripla is the grandparent of all the current single-tablet regimens (STRs) for HIV treatment. In 2006, it became the first pill containing a fully active regimen to be approved by the U.S. Food and Drug Administration (FDA).

When Atripla came on the scene, it was a game-changer for antiretroviral therapy (ART) as we knew it. Since 1997, we had been treating HIV using a “cocktail” (three, sometimes four, medications in combination that blocked HIV at different phases of its life cycle), which was highly effective in slowing down the virus. That was the standard of care—but multiple-pill combinations that needed to be taken two or three times daily, combined with significant side effects, made adherence challenging and left folks living with HIV feeling like they were exchanging one disease for another.

While coformulated options like Combivir (which contains two older HIV meds) and Trizivir (which contains three) had been developed and were helpful in reducing pill burden, they still had to be taken twice daily—and the older medications they contained, like AZT, came with many side effects. The arrival of Atripla as a full ART regimen in a one-pill, once-a-day formulation changed all that, putting HIV on track to becoming the chronic, manageable, and significantly easier-to-treat condition many consider it to be today.

Atripla contains three HIV medications:

• TDF, also commonly referred to as Viread or by the generic name tenofovir disoproxil fumarate, was first FDA-approved for use in HIV treatment in 2001.

• FTC, also known as Emtriva or emtricitabine, has been on the market since 2003.

• EFV, also known as Sustiva or efavirenz, was FDA-approved in 1998 for use, like TDF and FTC, in combination HIV treatment with other medications.

TDF and FTC were combined into a pill called Truvada, which was FDA-approved in 2004 and became the accepted staple of ART in a multitude of STRs, beginning with Atripla in 2006 (after years of EFV and Truvada being utilized as separate pills taken in tandem).

Atripla Can Be Useful Against Hepatitis B

One of the benefits of including TDF and FTC together in Atripla as part of an ART regimen is not only its effectiveness in slowing down HIV, but its usefulness in the treatment of hepatitis B.

Both FTC and TDF are effective against hepatitis B, with FTC not being as strong a treatment medication by itself due to problems with resistance. TDF is a little more durable and less prone to resistance for the treatment of hepatitis B, so the two combined as part of Atripla is a good option for treatment if you are living with both HIV and hepatitis B.

Having your medical provider check your bloodwork for immunity to hepatitis B (if you have antibodies) or if you may have active hepatitis B will help with this decision. If you do have active hepatitis B, both you and your provider need to know that, as it confirms that Atripla will be useful in treating both HIV and hepatitis B. It’s also helpful to know this because sometimes when you stop the medication that is treating hepatitis B, you can experience an acute hepatitis B flare with symptoms such as nausea, abdominal pain, and vomiting.

Atripla Is No Longer a Major First-Line HIV Treatment Regimen

For years after its initial approval, Atripla enjoyed status as a recommended initial ART regimen within official U.S. HIV treatment guidelines for people who are ARV-naive (i.e., have never been on HIV meds before). Given that it was the new kid on the block and the first STR of its kind, clinicians and their patients flocked to it as a first-line regimen or to switch from traditional regimens involving multiple pills, food restrictions, and side effects.

It would be more than five years before the next STR, Complera, emerged on the scene to give Atripla competition in 2011. Over the past decade, the FDA has approved several other STRs, pushing Atripla to the back seat in many clinicians’ minds when it comes to initial treatment options.

Now Atripla is listed in the guidelines only as a “recommended initial regimen in certain clinical situations”—meaning it has certain disadvantages or lacks strong clinical data compared with other recommended initial regimens.

Why Don’t People Use Atripla as Much as They Used To?

While Atripla revolutionized ART as we knew it, it wasn’t without its own set of concerns and potential problems.

One big concern was over its use by people who were pregnant or might become pregnant. Early animal and case studies suggested that the EFV component of Atripla could cause complications to the fetus during the first trimester of pregnancy, prompting the FDA to change its safety profile from pregnancy category C to D.

This recommendation was based on retrospective reports, and the reputation of EFV being potentially harmful to fetuses stayed with it for years, so providers were reluctant to either prescribe or keep women with HIV on EFV or Atripla if they were of child-bearing age.

Over time, however, more data emerged to suggest that EFV and its risk to the fetus, particularly during the first trimester, was not as elevated as once described and that it was safe to start or keep pregnant women on Atripla.

But despite formal U.S. Department of Health and Human Services updates declaring the relative safety of Atripla and other EFV-containing ART regimens for pregnant women and their fetuses, the FDA has not modified its original recommendation. Moreover, the general public has not forgotten that initial pregnancy category label, thus leaving a lingering stigma over Atripla that has been hard for it to shake in recent years.

Another reason why Atripla has fallen out of favor has been the other documented neuropsychiatric side effects for people taking it. A review in 2007 noted a wide variety of potential side effects associated with EFV along the neuropsychiatric spectrum. These included:

• Acute psychosis.
• Dizziness.
• Major depression and/or anxiety.
• Sleep disturbances.
• Vivid dreams.

While increased suicidality has been linked to EFV use in some studies, others have not found this association. What is clear is that the potential for a broad spectrum of neuropsychiatric effects has been noted with this medication, which should be considered when making choices about treatment options.

Researchers found that many of these potential side effects appear to be connected to drug levels of EFV in the bloodstream, which can go up and down for a variety of reasons. The food restrictions that come with taking Atripla are based on EFV and its potential side effects: Taking EFV close to a meal slows down its metabolism in the body so that it lingers in the bloodstream. This makes EFV more potent in slowing down HIV but also gives it that much more time to cross over into the central nervous system and brain, where it can cause many of these side effects.

While some of the potential neuropsychiatric side effects can be dramatic, many are more subtle changes (i.e., sleep disturbances, moodiness) that people may just get used to over time, not realizing these are medication-related until they actually switch medications. Regardless, reports of these side effects have also diminished enthusiasm for Atripla over time.

Another consideration with Atripla is durability and issues with drug resistance. As a class of medications, NNRTIs like EFV have a lower genetic barrier to resistance than other classes, such as protease inhibitors (PIs) or integrase strand transfer inhibitors (INSTIs). Thus, in an STR like Atripla, where you are combining EFV with two NRTIs like TDF and FTC—which can also have issues with resistance when adherence is not always 100%—this can lead the virus to develop mutations more easily, and ultimately bring about resistance to some, if not all, of the medications in the regimen.

Finally, perhaps the most important reason why Atripla has fallen out of favor with both patients and prescribers alike has been the advancement of ART science itself. Since 2006, several alternative STRs have emerged and been FDA-approved for use in the treatment of HIV. Many are stronger and more potent, and some boast fewer medications and a higher genetic barrier to viral resistance.

In short, Atripla kicked open the door of STRs in HIV treatment in the mid-2000s, but it is now witnessing multiple, improved STRs pass it by due to scientific improvements in tolerability and strength.

How to Take Atripla

Atripla is FDA-approved in the United States to be taken once daily, on an empty stomach—which means two hours after a meal or one hour before a meal. Also, because of the potential neuropsychiatric effects, notably dizziness, difficulty concentrating, and muddled thinking, many prescribers also recommend patients take it an hour or so before bedtime. This way, if there are any neuropsychiatric effects, people will sleep through them.

How Much Does Atripla Cost in the U.S.?

Atripla contains 600 mg efavirenz, 200 mg emtricitabine, and 300 mg tenofovir disoproxil fumarate. The price is approximately $3,136 for a month’s supply.

If you have insurance, monthly copays for Atripla can typically run between $50 and $100 depending on the plan, though you may qualify for cost-sharing assistance provided by the manufacturer.

If you don’t have insurance, or your insurance won’t cover the majority of Atripla’s cost (you are “underinsured”), there is a patient assistance program that can help reduce or eliminate the cost, depending on your financial situation.

A single generic version of Atripla became available in the U.S. in October 2020. When there is only one generic competitor, the price may only be somewhat lower than the brand-name version of the drug. Competition involving multiple generic versions of EFV/TDF/FTC is expected to begin sometime in 2021.

Side Effects of Atripla

As with many ART regimens, there is the potential for mild side effects, particularly when first starting out on meds or switching to Atripla. Symptoms like an upset stomach, mild rash, nausea, or diarrhea may occur.

A general rule of thumb is what we call “the two-week rule”: When starting your HIV treatment regimen, give your body about two weeks for it to get adjusted to the medication. Sometimes rashes, mild fever, joint pain, or other symptoms may happen, and this could be related to the medication working and your immune system getting stronger as a result—manifesting as these symptoms. Keep in touch with your medical team and let them know as you move forward.

If, however, after a couple of weeks, you are still having bothersome symptoms or they are progressing, let someone from your medical team know so that you can schedule a virtual or in-person meeting to discuss. In this day and age, we have varying options for HIV treatment, and it is possible that even if a medication worked well for one of your friends, that doesn’t necessarily mean that your body will respond to it in the same way. Speak up, let your provider know, and discuss whether they recommend labs or switching up your regimen altogether.

There are very rare concerns of buildup of lactic acid in the blood or liver problems when taking Atripla, so pay attention to any new or worsening symptoms of fever, abdominal pain, nausea/vomiting, or unusual muscle aches.

Specific side effects of concern that have come up with Atripla are the ones we mentioned earlier that are associated specifically with EFV:

• The potential for fetal harm when used during the first trimester of pregnancy, though this remains unproven.
• Neuropsychiatric side effects.

As for the other two medications within Atripla: FTC is remarkably well tolerated, and the TDF component of Atripla carries the same rare but potential risk of kidney damage and bone thinning as when it is prescribed separately or as part of Truvada.

Given the side effects with Atripla in its current dosing form, studies have been conducted evaluating Atripla against the same regimen with a lower dose of EFV (400 mg instead of 600 mg). Researchers found that the regimen with the lower dose of EFV was equally effective as the standard dose and with less frequent side effects. As a result, that lower-dose form of Atripla was FDA-approved in 2018 as an HIV-treatment regimen named Symfi Lo. (Symfi Lo contains 3TC [a.k.a. lamivudine or Epivir] instead of FTC, but the two are largely considered interchangeable.)

Interactions Between Atripla and Other Drugs

Atripla is an STR that does not have a boosting medication in it (e.g., cobicistat or ritonavir), so no concerns from that perspective. Similarly, FTC and TDF have a small number of potential drug interactions.

Due to the potential of neuropsychiatric side effects of EFV, however, care should be taken when considering taking other neuropsychiatric medications such as benzodiazepines, opiates, anticonvulsants, mood stabilizers, and sleep aids—all of which may heighten dizziness or other sedation-related side effects of Atripla.

Additionally, there are some antifungal medications that should not be taken with Atripla, such as voriconazole and other “azole” medications.

A great website to utilize if you want to check specific medications and how they may interact with the components of Atripla is the website HIV Drug Interactions, which is maintained by the University of Liverpool.

What’s the Verdict on Atripla?

Atripla was the first highly effective STR to come on the market, back in 2006. For years, it enjoyed elevated status as the only one-pill, once-a-day regimen for the treatment of HIV. As the years passed, it has fallen out of favor due to the approval of newer, shinier STRs with a more desirable side-effect profile and better durability, as well as lingering concerns regarding its disproven association with a heightened risk for birth defects.

It is also true that Atripla contains TDF, which has been associated with rare but potential risks to both kidney health and bone loss. And the EFV component of Atripla has been associated with an increased likelihood of neuropsychiatric effects such as sleep disturbances, mood swings, depression, and others.

Despite all this, Atripla is still very effective at HIV viral suppression, and it’s well-tolerated by many persons living with HIV who fully embrace the notion of, “If it ain’t broke, don’t fix it,” and, “The grass ain’t always greener on the other side.” Indeed, may people living with HIV who were prescribed Atripla many years ago are continuing to use it safely and effectively.

As with all ART regimens, while the studies may say one thing and your friends may have certain reactions to medications, your body is your body. Just because something doesn’t work for someone else doesn’t mean it won’t be a good option for you. Atripla may be the grandparent of STRs with HIV treatment, but that doesn’t necessarily mean it ain’t still got it. Respect your elders.