Treatment for HIV has come a long way. In the 1980s, HIV was considered a fatal disease. 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 drug cocktails that used to be the only option for people with HIV.

In 1987, the very first drug was approved to treat HIV. It was called azidothymidine, or AZT. AZT is an antiretroviral drug, a type that 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 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, AZT was the most expensive medication in history, costing users $8,000 to $10,000 per year ($17,825 to $22,282 per year in 2018 dollars).

It leads to significant and potentially serious side effects in some people. And when the drug is used by itself, HIV quickly becomes resistant, allowing disease recurrence.

Other HIV drugs followed, 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 HIV-positive people 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. This therapy was called highly active antiretroviral therapy (HAART). It’s now also called combination antiretroviral therapy (cART) and uses a cocktail of drugs.

The drugs come from at least two different drug classes.

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, then they’ll have “effectively no risk” of sexually transmitting HIV to others. This is according to the Centers for Disease Control and Prevention (CDC).

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

  • Entry inhibitors and fusion inhibitors. These drugs stop HIV from getting into cells of the immune system in the first place.
  • Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs or “nukes”). NRTIs prevent the virus from copying its genetic material. NRTIs block an enzyme called reverse transcriptase. HIV uses reverse transcriptase to convert RNA (its genetic material).
  • Non-nucleoside reverse transcriptase inhibitors (NNRTIs or “non-nukes”). NNRTIs also block the virus from converting its genetic material with reverse transcriptase. However, they work differently from NRTIs.
  • Integrase inhibitors. These drugs block an enzyme the virus needs to insert copies of its genes into a human cell’s genetic material.
  • Protease inhibitors. These drugs 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.

In the past, people on antiretroviral medications needed to take several different pills each 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 combination drugs. It contains lamivudine (NRTI) and zidovudine (NRTI). Currently, seventeen combination tablets are approved to treat HIV. Some examples include:

  • Atripla, which contains efavirenz (NNRTI), emtricitabine (NRTI), and tenofovir disoproxil fumarate (NRTI)
  • Biktarvy, which contains bictegravir (integrase inhibitor), emtricitabine (NRTI), and tenofovir alafenamide (NRTI)
  • Cimduo, which contains lamivudine (NRTI) and tenofovir disoproxil fumarate (NRTI)
  • Complera, which contains emtricitabine (NRTI), rilpivirine (NNRTI), and tenofovir disoproxil fumarate (NRTI)
  • Descovy, which contains emtricitabine (NRTI) and tenofovir alafenamide (NRTI)
  • Genvoya, which contains elvitegravir (integrase inhibitor), cobicistat, emtricitabine (NRTI), and tenofovir alafenamide (NRTI)
  • Juluca, which contains dolutegravir (integrase inhibitor) and rilpivirine (NNRTI)
  • Odefsey, which contains emtricitabine (NRTI), rilpivirine (NNRTI), and tenofovir alafenamide (NRTI)
  • Stribild, which contains elvitegravir (integrase inhibitor), cobicistat, emtricitabine (NRTI), and tenofovir disoproxil fumarate (NRTI)
  • Symfi, which contains efavirenz (NNRTI), lamivudine (NRTI), and tenofovir disoproxil fumarate (NRTI)
  • Triumeq, which contains dolutegravir (integrase inhibitor), abacavir (NRTI), and lamivudine (NRTI)
  • Truvada, which contains emtricitabine (NRTI) and tenofovir disoproxil fumarate (NRTI)

Taking just 1 daily pill instead of 3 or 4 simplifies treatment for people with HIV. It also improves its effectiveness.

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

In addition, fixed-dose combinations cut down on dosing errors. They also lower the likelihood that HIV will become resistant to the treatment.

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 someone develops a side effect, it can be hard to tell which of the drugs in the 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, HIV-positive people may want to discuss the benefits and risks of single tablets versus a combination pill. A healthcare provider can help them choose the option that best suits their lifestyle and health.