Treatment for HIV has come a long way. In the 1980s, HIV was considered fatal. Thanks to advances in treatment, HIV has become more of a chronic condition, much like heart disease or diabetes.

One of the biggest recent advances in HIV treatment has been the development of a single-dose medication — one pill that contains a combination of several different HIV drugs.

A combination pill is a big step forward from the cumbersome, multi-pill drug regimens that used to be the only option for people with HIV.

Some combination pills still need to be taken with other antiretroviral drugs to be effective. An example is emtricitabine and tenofovir disoproxil fumarate (Truvada).

Other combination pills form a complete HIV regimen all on their own. Examples include pills that combine three different drugs, such as efavirenz, emtricitabine, and tenofovir disoproxil fumarate (Atripla). Some newer two-drug combinations, such as dolutegravir and rilpivirine (Juluca), also form a complete HIV regimen.

One important difference between two-drug combinations such as Juluca and two-drug combinations such as Truvada is that Juluca includes two drugs from different drug classes. The two drugs in Truvada belong to the same drug class.

When a person is prescribed a combination pill that can be used as a complete HIV regimen, it’s known as a single-tablet regimen (STR).

In 1987, the Food and Drug Administration (FDA) approved the very first drug to treat HIV. It was called azidothymidine, or AZT (now referred to as zidovudine).

AZT is an antiretroviral drug, which helps prevent the virus from copying itself. By lowering the amount of HIV in the body, antiretroviral drugs help keep the immune system strong.

AZT is part of a class of antiretroviral drugs called nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs).

The introduction of AZT was a major advancement in HIV treatment, but it isn’t a perfect drug. At the time it was introduced, AZT was the most expensive medication in history, costing users $8,000 to $10,000 per year (roughly $18,000 to $23,000 per year in 2019 dollars).

This drug can lead to significant and potentially serious side effects in some people. Moreover, when AZT is used by itself, HIV quickly becomes resistant. This drug resistance allows disease recurrence.

AZT now goes by the name zidovudine and is still on the market today, but it isn’t commonly used in adults. Babies born to HIV-positive mothers may receive post-exposure prophylaxis (PEP) with AZT.

Other HIV drugs followed AZT, including protease inhibitors. These drugs work by stopping HIV from making more viruses inside cells that are already affected by HIV.

Healthcare providers soon discovered that when people with HIV were given only one drug at a time, HIV became resistant to it, making the drug ineffective.

By the end of the 1990s, single-drug therapy gave way to combination treatment. Combination treatment incorporates at least two different HIV drugs. These drugs are often from different classes, so they have at least two different ways of stopping the virus from making copies of itself.

This therapy was historically called highly active antiretroviral therapy. It’s now called antiretroviral therapy or combination antiretroviral therapy. It previously required what was referred to as “a cocktail of drugs” in the form of handfuls of pills, often taken multiple times per day. Now, a person living with HIV may be prescribed a single combination pill.

Effective combination therapy reduces the amount of HIV in a person’s body. Combination regimens are designed to maximize the level of HIV suppression while minimizing the likelihood of the virus becoming resistant to any one drug.

If an HIV-positive person is able to achieve viral suppression through HIV treatment, the Centers for Disease Control and Prevention (CDC) says they’ll have “effectively no risk” of transmitting HIV to others sexually.

Today, multiple different classes of antiretroviral drugs are used in various combinations to treat HIV. All of the drugs in these classes interfere with how HIV copies itself in different ways:

  • Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs, or “nukes”). NRTIs prevent the virus from copying its genetic material. NRTIs block an enzyme called reverse transcriptase, which HIV uses to convert its genetic material (RNA) to DNA.
  • Integrase strand transfer inhibitors (INSTIs). INSTIs are a category of integrase inhibitor specifically used to treat HIV. Integrase inhibitors block an enzyme, integrase, that viruses need to insert copies of its genes into a human cell’s genetic material.
  • Protease inhibitors (PIs). PIs block an enzyme called protease, which the virus needs to process proteins that are essential to its ability to make more virus. These drugs severely limit HIV’s ability to replicate.
  • Non-nucleoside reverse transcriptase inhibitors (NNRTIs, or “non-nukes”). NNRTIs also block the virus from converting RNA, its genetic material, to DNA with reverse transcriptase. However, they work differently from NRTIs.
  • Entry inhibitors. Entry inhibitors stop HIV from getting into cells of the immune system in the first place. This broad category of drugs includes drugs from the following classes: chemokine coreceptor antagonists (CCR5 antagonists), fusion inhibitors, and post-attachment inhibitors. Although these antiretrovirals stop HIV from one of the first steps in making copies of itself, these medications are often saved for when a person is running out of options due to many drug-resistant mutations of HIV.

The HIV drugs ritonavir and cobicistat belong to a class of drugs known as cytochrome P4503A inhibitors, or CYP3A inhibitors. They both function primarily as booster drugs: When taken alongside other HIV drugs, ritonavir and cobicistat enhance the effects of those other drugs. Ritonavir also belongs to the PI drug class.

In the past, people on antiretroviral medications needed to take several different pills each day, often multiple times per day. The complicated regimen often led to mistakes, missed doses, and less effective treatment.

Fixed-dose combinations of HIV drugs became available in 1997. These drugs combine two or more drugs from the same or different classes into one pill. The single pill is easier to take.

Combivir was the first of these brand-name combination drugs. Currently, 23 combination tablets are approved to treat HIV. Keep in mind that some of them may need to be taken with other antiretroviral drugs to form a complete HIV regimen.

The FDA-approved combination tablets are:

  • Atripla, which contains efavirenz (NNRTI), emtricitabine (NRTI), and tenofovir disoproxil fumarate (NRTI)
  • Biktarvy, which contains bictegravir (INSTI), emtricitabine (NRTI), and tenofovir alafenamide fumarate (NRTI)
  • Cimduo, which contains lamivudine (NRTI) and tenofovir disoproxil fumarate (NRTI)
  • Combivir, which contains lamivudine (NRTI) and zidovudine (NRTI)
  • Complera, which contains emtricitabine (NRTI), rilpivirine (NNRTI), and tenofovir disoproxil fumarate (NRTI)
  • Delstrigo, which contains doravirine (NNRTI), lamivudine (NRTI), and tenofovir disoproxil fumarate (NRTI)
  • Descovy, which contains emtricitabine (NRTI) and tenofovir alafenamide fumarate (NRTI)
  • Dovato, which contains dolutegravir (INSTI) and lamivudine (NRTI)
  • Epzicom, which contains abacavir (NRTI) and lamivudine (NRTI)
  • Evotaz, which contains atazanavir (PI) and cobicistat (CYP3A inhibitor)
  • Genvoya, which contains elvitegravir (INSTI), cobicistat (CYP3A inhibitor), emtricitabine (NRTI), and tenofovir alafenamide fumarate (NRTI)
  • Juluca, which contains dolutegravir (INSTI) and rilpivirine (NNRTI)
  • Kaletra, which contains lopinavir (PI) and ritonavir (PI/CYP3A inhibitor)
  • Odefsey, which contains emtricitabine (NRTI), rilpivirine (NNRTI), and tenofovir alafenamide fumarate (NRTI)
  • Prezcobix, which contains darunavir (PI) and cobicistat (CYP3A inhibitor)
  • Stribild, which contains elvitegravir (INSTI), cobicistat (CYP3A inhibitor), emtricitabine (NRTI), and tenofovir disoproxil fumarate (NRTI)
  • Symfi, which contains efavirenz (NNRTI), lamivudine (NRTI), and tenofovir disoproxil fumarate (NRTI)
  • Symfi Lo, which contains efavirenz (NNRTI), lamivudine (NRTI), and tenofovir disoproxil fumarate (NRTI)
  • Symtuza, which contains darunavir (PI), cobicistat (CYP3A inhibitor), emtricitabine (NRTI), and tenofovir alafenamide fumarate (NRTI)
  • Temixys, which contains lamivudine (NRTI) and tenofovir disoproxil fumarate (NRTI)
  • Triumeq, which contains abacavir (NRTI), dolutegravir (INSTI), and lamivudine (NRTI)
  • Trizivir, which contains abacavir (NRTI), lamivudine (NRTI), and zidovudine (NRTI)
  • Truvada, which contains emtricitabine (NRTI) and tenofovir disoproxil fumarate (NRTI)

Taking just one daily combination pill instead of two, three, or four pills simplifies treatment for people with HIV. It also improves the effectiveness of the drugs.

A 2012 study of over 7,000 people with HIV found that those who take a single daily combination pill are less likely than those who take three or more daily pills to get sick enough to end up in the hospital.

A 2018 study of over 1,000 people with HIV also compared people on single-tablet regimens to people on multi-tablet regimens. The researchers concluded that people on single-tablet regimens were more likely to stick to their regimens and to experience viral suppression.

On the other hand, adding more drugs to one pill can also lead to more side effects. That’s because each drug comes with its own set of risks. If a person develops a side effect from a combination pill, it can be hard to tell which of the drugs in the combination pill caused it.

Choosing an HIV treatment is an important decision. People living with HIV can make their decision with the help of their healthcare providers.

Before deciding on a treatment, you may want to discuss the benefits and risks of single tablets versus a combination pill. A healthcare provider can help you choose the option that best suits your lifestyle and health.