Treatment for HIV infection has come a long way. In the 1980s, HIV infection was considered a fatal infection. Thanks to advances in treatment, HIV infection 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.

The first drug

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 HIV 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 ($17,000 to $21,000 per year in today’s dollars). It has significant and potentially serious side effects in some people. And when the drug is used by itself, HIV eventually becomes resistant, allowing disease recurrence.

Single-drug therapy

Other HIV drugs followed, including protease inhibitors. These drugs work by stopping the HIV virus from making more viruses inside already-infected cells. Doctors soon discovered that when patients were given only one drug at a time, HIV became resistant to it, making the drug ineffective.

Combination treatments

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.

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, which HIV uses to copy RNA, its genetic material.
  • Non-nucleoside reverse transcriptase inhibitors (NNRTIs or “non-nukes”): NNRTIs also block the virus from copying its genetic material with reverse transcriptase, but 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 HAART needed to take several different pills each day. The complicated regimen often led to mistakes, missed doses, and less effective treatment.

Since 2006, fixed-dose combinations of HIV drugs have become available. These drugs combine two or more drugs from the same or different classes into one pill. The single pill is easier to take.

Currently, four combination tablets are approved to treat HIV:

  • Atripla, which contains efavirenz (NNRTI), emtricitabine (NRTI), and tenofovir disoproxil fumarate (NRTI)
  • Complera, which contains emtricitabine (NRTI), rilpivirine (NNRTI), and tenofovir disoproxil fumarate (NRTI)
  • Stribild, which contains elvitegravir (integrase inhibitor), cobicistat, emtricitabine (NRTI), and tenofovir disoproxil fumarate (NRTI)
  • Triumeq, which contains dolutegravir (integrase inhibitor), abacavir (NRTI), and lamivudine (NRTI)

Taking just 1 daily pill instead of 3 or 4 simplifies treatment for people with HIV. It also improves its effectiveness. A study found that people who take a single daily pill are less likely than people 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 the HIV virus 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 you develop 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. You should make your decision with your doctor. Discuss the benefits and risks of single tablets versus a combination pill. Choose the option that best suits your lifestyle and health.