What Are the Benefits of a Single-Tablet Therapy for HIV?

The treatment of HIV has traditionally been complicated as it requires multiple antiretroviral drugs to fully suppress the virus. Therapies typically involved three or more drugs from at least two different classes, each with distinct mechanisms of action and drug half-lives (the speed by which the drug is eliminated from the body).

In the past, this posed serious problems as older drugs like Crixivan (indinavir) required three pills every eight hours, while others like Zerit (stavudine) and Epivir (lamivudine) required dosing every 12 hours. For a therapy like this, you would need to take a dose four to five times a day, every day to achieve viral suppression.

Today, these concerns have largely been overcome as improved pharmacokinetics have extended the half-life of many of the drugs, allowing them to be taken once daily without the risk of toxicity. There are even therapies today that require only two rather than the traditional three drugs to achieve the same durable suppressive effect.

On top of this, more and more antiretrovirals are being co-formulated into combination tablets that have reduced the pill burden to as few as one pill daily. Clearly, by taking fewer pills, managing HIV becomes far easier and less impactful on your life and well-being.

But the benefits extend well beyond the ease of use.

Fixed-Dose Combination Tablets

Today, there are over 25 different antiretroviral drugs approved by the U.S. Food and Drug Administration (FDA). Many of these individual agents have been co-formulated into fixed-dose combination (FDC) tablets that are either used on their own or with other antiretroviral drugs.

Of the 22 FDC tablets approved by the FDA, 13 can be used on their own as a complete, once-daily therapy:

• Atripla (efavirenz + emtricitabine + tenofovir DF)
• Biktarvy (bictegravir + emtricitabine + tenofovir AF)
• Complera (emtricitabine + rilpivirine + tenofovir DF)
• Delstrigo (doravirine + lamivudine + tenofovir DF)
• Dovato (dolutegravir + lamivudine)
• Genvoya (cobicistat + elvitegravir + emtricitabine + tenofovir AF)
• Juluca (dolutegravir + rilpivirine)
• Odefsey (emtricitabine + rilpivrine + tenofovir AF)
• Stribild (cobicistat + elvitegravir + emtricitabine + tenofovir DF)
• Symfi (efavirenz + lamivudine + tenofovir DF)
• Symfi Lo (efavirenz + lamivudine + tenofovir DF)
• Symtuza (cobicistat + darunavir + FTC + TAF)
• Triumeq (abacavir + dolutegravir + lamivudine)

Pill Burden and Adherence

The first major benefit of a once-daily, single-pill regimen is the ease of use. You simply take one pill in the morning (or sometimes before bedtime) and that's it for the day.

This greatly improves treatment adherence (the practice of taking your drugs as prescribed on a regular basis). This, in turn, reduces the risk of drug resistance by ensuring that the concentration of drugs in your body remains at a constant therapeutic level.

By maintaining a consistent concentration, the virus is suppressed to undetectable levels and drug-resistant strains are less able to "escape" and proliferate. To achieve this, most experts recommend greater than 95% adherence (or roughly one missed dose per month).

This poses a serious concern to health authorities as roughly one-in-three people on antiretroviral therapy in the United States are unable to achieve an undetectable viral load, according to statistics from the Department of Health and Human Service.

By reducing the daily pill burden to one tablet daily, studies have shown the rate of adherence can be significantly increased along with the rates of viral suppression.

Pill Burden and Hospitalization

Beyond the issue of drug resistance, taking one pill daily appears to improve the overall health of people living with HIV.

A 2016 study from the University of South Carolina examined the relationship between antiretroviral pill burden and the rate of hospitalizations among 2,174 Medicaid recipients in South Carolina from 2006 to 2013. In total, 580 people were on a single-pill regimen, while 1,594 were prescribed a multi-pill regimen involving two or more drugs.

According to the researchers, people on the single-pill regimen had higher rates of complete viral suppression (64.5% vs 49.5%) and experience 29% fewer hospitalizations compared to those on a multi-pill regimen.

A similar study from the University of North Carolina, Chapel Hill in 2013 concluded that a high pill burden is linked to increased rates of non-HIV-associated illnesses in people with HIV.  (Today, non-HIV-associated diseases like cancer and heart disease are the leading causes of death in people living with HIV in the developed world.)

Limitations of Use

As attractive as the daily one-pill option may seem, not everyone is a candidate. There are several factors that can limit their use, whether you are being newly treated for HIV or changing treatment. These include:

• Drug resistance: Prior to starting a new therapy, you will undergo genetic resistance testing to see which drugs you are resistant to. Even if you are newly infected, it is possible to acquire a resistant mutation that limits the number of drugs you are sensitive to.
• Drug contraindications: Certain pre-existing health conditions may disqualify certain drugs, including the use of tenofovir in people with severe kidney disease or the use of efavirenz in people with serious psychiatric conditions.
• Drug hypersensitivity: With abacavir, genetic testing is performed to ensure that you don't have the HLA-B*5701 mutation which predicts the likelihood of a serious and potentially life-threatening drug hypersensitivity reaction.
• Drug tolerability: Some people will tolerate certain drugs better than others. If side effects are severe or intolerable, the drug may need to be discontinued.

Despite these limitations, the increasing number of FDC drugs means that newly treated people are more likely than not to find a once-daily option that works.

Another limiting factor is cost. Many all-in-one antiretrovirals are placed on a high tier on insurance drug formularies, requiring higher out-of-pocket copay or coinsurance costs. Although manufacturer assistance programs are available, the assistance may still not be enough to make the drug affordable to the underinsured or uninsured.

Advances in Treatment

In January 2021, the very concept of antiretroviral treatment was turned on its ear with the approval of the first once-monthly therapy called Cabenuva. Delivered by injection—with one shot of the drug rilpivirine and one shot of a novel integrase inhibitor cabotegravir—Cabenuva has been shown to provide the same level of viral control as traditional once-daily antiretroviral therapy.

The cost of treatment may be an impediment given the monthly average wholesale price of Cabenuva is $4,754. Moreover, it is unclear if health insurers will add it to their drug formularies and under what conditions.

It is also unclear if going into your doctor's office monthly for a shot is necessarily more convenient than taking your pills every day at home.

Even so, Cabenuva can better ensure adherence in people unable to do so on their own, while providing doctors a means to track adherence and intervene when necessary.

A Word From Verywell

As attractive as a once-daily, single-pill option sounds, don't change treatment simply for the sake of changing. If you are able to sustain an undetectable viral load on your current therapy, it may be better to stay the course.

If, on the other hand, you have been struggling with adherence (such can occur if you have an irregular work schedule), ask your doctor if a single-pill option is right for you. Anything that makes it easier for you to take your drugs is likely to improve their effectiveness and durability.