The Evolution of HIV Treatments: How They Work, HAART, and More

Thirty years ago, healthcare providers had little more than comforting words to offer people who'd been diagnosed with HIV. Today it's a manageable health condition.

There's no HIV or AIDS cure yet. However, remarkable advancements in treatments and clinical understanding of how HIV progresses are allowing people with HIV to live longer, fuller lives.

Let's look at where HIV treatment is today, the effects new therapies are having, and where treatment may be headed in the future.

The main treatment for HIV today is antiretroviral drugs. These drugs don't cure HIV. Instead, they suppress the virus and slow its progression in the body. Although they don't eliminate HIV from the body, they can suppress it to undetectable levels in many cases.

If an antiretroviral drug is successful, it can add many healthy, productive years to a person's life and reduce the risk of transmission to others.

First-line treatments that are commonly prescribed to people beginning antiretroviral therapy can be divided into four drug classes:

• reverse transcriptase (RT) inhibitors
• protease inhibitors (PIs)
• entry or fusion inhibitors
• integrase inhibitors

The drugs listed below have all been approved by the Food and Drug Administration (FDA) to treat HIV.

Reverse transcriptase (RT) inhibitors

Reverse transcriptase (RT) inhibitors interrupt the life cycle of an HIV-infected cell as it tries to replicate itself. There are two types of RT inhibitor: NNRTIs and NRTIs.

Non-nucleoside reverse transcriptase inhibitors (NNRTIs)

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) prevent HIV from making copies of itself. Commonly used NNRTIs include:

• efavirenz (Sustiva)
• rilpivirine (Endurant)
• etravirine (Intelence)

Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs)

Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) keep HIV-infected cells from making copies of themselves by interrupting the reconstruction of the virus's DNA chain. Some examples of commonly used NRTIs include:

• abacavir (Ziagen)
• lamivudine (Epivir)
• emtricitabine (Emtriva)
• tenofovir disoproxil fumarate (Viread)
• tenofovir alafenamide fumarate (Vemlidy)

Tenofovir alafenamide fumarate is used in multiple combination pills for HIV. As a stand-alone drug, it's only received tentative approval to treat HIV. The stand-alone drug has been FDA-approved to treat chronic hepatitis B infection.

Commonly used combination NRTIs include:

• emtricitabine/tenofovir disoproxil fumarate (Truvada)
• emtricitabine/tenofovir alafenamide fumarate (Descovy)
• abacavir/lamivudine (Epzicom)

Protease inhibitors (PIs)

Protease inhibitors (PIs) disable protease, a protein that HIV needs as part of its life cycle. PIs include:

• atazanavir (Reyataz)
• darunavir (Prezista)
• ritonavir (Norvir)
• lopinavir (combined with ritonavir in the brand-name drug Kaletra)
• saquinavir (Invirase)
• tipranavir (Aptivus)

Entry or fusion inhibitors

Entry or fusion inhibitors block HIV from entering CD4 T cells. These inhibitors include:

• maraviroc (Selzentry)
• enfuvirtide (Fuzeon)
• ibalizumab (Trogarzo)

Integrase inhibitors

Integrase inhibitors disable integrase, a protein that HIV uses to infect CD4 T cells.

Categories of integrase inhibitors include integrase strand transfer inhibitors (INSTIs) and integrase binding inhibitors (INBIs), among others. INSTIs are well-established drugs, while the other categories of integrase inhibitors are considered experimental drugs.

INSTIs include:

• bictegravir (combined with tenofovir alafenamide fumarate and emtricitabine in the brand-name drug Biktarvy)
• dolutegravir (Tivicay)
• elvitegravir (combined with cobicistat, tenofovir alafenamide fumarate, and emtricitabine in the brand-name drug Genvoya, or with cobicistat, tenofovir disoproxil fumarate, and emtricitabine in the brand-name drug Stribild)
• raltegravir (Isentress, Isentress HD)

HIV can mutate and become resistant to a single medication. Therefore, most healthcare providers today prescribe several HIV medications together.

A combination of three or more antiretroviral drugs is called highly active antiretroviral therapy (HAART). It's the typical initial treatment prescribed today for people with HIV.

This powerful therapy was first introduced in 1995. Because of HAART, AIDS-related deaths in the United States were cut by 47 percent between 1996 and 1997.

The most common HAART treatments today consist of two NRTIs and either an INSTI, an NNRTI, or a PI boosted with cobicistat.

Advances in medications are also making adherence to HAART much easier. These advances have reduced the number of pills a person must take. They've also reduced the side effects for many people using HAART.

One key advancement that's making adherence easier for people on HAART is the development of combination pills. These medications are now the most commonly prescribed drugs for people with HIV who haven't been treated before.

Combination pills contain multiple drugs within one pill. Currently, there are 12 combination pills containing three or more antiretroviral drugs:

Atripla:

• 600 milligrams (mg) efavirenz
• 200 mg emtricitabine
• 300 mg tenofovir disoproxil fumarate

Biktarvy:

• 50 mg bictegravir
• 200 mg emtricitabine
• 25 mg tenofovir alafenamide fumarate

Complera:

• 200 mg emtricitabine
• 25 mg rilpivirine
• 300 mg tenofovir disoproxil fumarate

Delstrigo:

• 100 mg doravirine
• 300 mg lamivudine
• 300 mg tenofovir disoproxil fumarate

Genvoya:

• 150 mg elvitegravir
• 150 mg cobicistat
• 200 mg emtricitabine
• 10 mg tenofovir alafenamide fumarate

Odefsey:

• 200 mg emtricitabine
• 25 mg rilpivirine
• 25 mg tenofovir alafenamide fumarate

Stribild:

• 150 mg elvitegravir
• 150 mg cobicistat
• 200 mg emtricitabine
• 300 mg tenofovir disoproxil fumarate

Symtuza:

• 800 mg darunavir
• 150 mg cobicistat
• 200 mg emtricitabine
• 10 mg tenofovir alafenamide fumarate

Symfi:

• 600 mg efavirenz
• 300 mg lamivudine
• 300 mg tenofovir disoproxil fumarate

Symfi Lo:

• 400 mg efavirenz
• 300 mg lamivudine
• 300 mg tenofovir disoproxil fumarate

Triumeq:

• 600 mg abacavir
• 50 mg dolutegravir
• 300 mg lamivudine

Trizivir:

• 300 mg abacavir
• 150 mg lamivudine
• 300 mg zidovudine

Atripla, which was FDA-approved in 2006, was the first effective combination tablet. However, it's used less often now due to side effects such as sleep disturbances and mood changes.

INSTI-based combination tablets are the regimens recommended now for most people with HIV. This is because they're effective and cause fewer side effects than other regimens. Examples include Genvoya and Stribild.

Though combination pills are a promising advancement, they may not be a good fit for every person with HIV. Discuss these options with a healthcare provider.

Each year, new therapies are gaining more ground in treating and possibly curing HIV and AIDS.

For instance, nanosuspensions of antiretrovirals are being investigated for both HIV treatment and prevention. These medications would be taken every four to eight weeks. They could improve adherence and reduce the number of pills people need to take.

Leronlimab, a weekly injection for people who've become resistant to HIV treatment, has seen success in clinical trials. It's also received a 'Fast Track' designation from the FDA, which will speed up the drug development process.

A monthly injection that combines rilpivirine with the new INSTI cabotegravir is scheduled to become available in early 2020.

There's also ongoing work on a potential HIV vaccine.

To find out more about HIV drugs that are currently available (and those that may come in the future), talk to a healthcare provider or pharmacist.

Clinical trials, which are used to test drugs in development, may also be of interest. Search here for a local clinical trial that may be a good fit.