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Antiretroviral therapy

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Antiretroviral therapy


HIV can mutate and become resistant to a single medication. Therefore most healthcare professionals today prescribe several HIV medications together.
A combination of two or more antiretroviral drugs is called antiretroviral therapy. It’s the typical initial treatment prescribed today for people with HIV.
This powerful therapy was first introduced in 1995. Because of antiretroviral therapy AIDS-related deaths in the United States were cut by 47 percent between 1996 and 1997.
The most common regimens today consist of two NRTIs and either an INSTI an NNRTI or a PI boosted with cobicistat (Tybost). There is new data supporting the use of only two drugs too such as an INSTI and an NRTI or an INSTI and an NNRTI.
Advances in medications are also making drug adherence much easier. These advances have reduced the number of pills a person must take. They’ve reduced the side effects for many people using antiretroviral medications. Lastly advancements have included improved drug-drug interaction profiles.

Combination pills


One key advancement that’s making adherence easier for people undergoing antiretroviral therapy 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 11 combination pills that contain two antiretroviral drugs. There are 12 combination pills containing three or more antiretroviral drugs:
Atripla (efavirenz emtricitabine and tenofovir disoproxil fumarate)Biktarvy (bictegravir emtricitabine and tenofovir alafenamide fumarate)Cimduo (lamivudine and tenofovir disoproxil fumarate)Combivir (lamivudine and zidovudine)Complera (emtricitabine rilpivirine and tenofovir disoproxil fumarate)Delstrigo (doravirine lamivudine and tenofovir disoproxil fumarate)Descovy (emtricitabine and tenofovir alafenamide fumarate)Dovato (dolutegravir and lamivudine)Epzicom (abacavir and lamivudine)Evotaz (atazanavir and cobicistat)Genvoya (elvitegravir cobicistat emtricitabine and tenofovir alafenamide fumarate)Juluca (dolutegravir and rilpivirine)Kaletra (lopinavir and ritonavir)Odefsey (emtricitabine rilpivirine and tenofovir alafenamide fumarate)Prezcobix (darunavir and cobicistat)Stribild (elvitegravir cobicistat emtricitabine and tenofovir disoproxil fumarate)Symfi (efavirenz lamivudine and tenofovir disoproxil fumarate)Symfi Lo (efavirenz lamivudine and tenofovir disoproxil fumarate)Symtuza (darunavir cobicistat emtricitabine and tenofovir alafenamide fumarate)Temixys (lamivudine and tenofovir disoproxil fumarate)Triumeq (abacavir dolutegravir and lamivudine)Trizivir (abacavir lamivudine and zidovudine)Truvada (emtricitabine and tenofovir disoproxil fumarate)
Atripla which was FDA-approved in 2006 was the first effective combination tablet to include three antiretroviral drugs. 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 Biktarvy Triumeq and Genvoya.
A treatment plan that includes a combination tablet made up of three antiretroviral drugs may also be referred to as a single-tablet regimen (STR).
An STR has traditionally referred to treatment with three antiretroviral drugs. However some newer two-drug combinations (such as Juluca and Dovato) include drugs from two different classes and have been FDA-approved as complete HIV regimens. As a result they’re also considered STRs.
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 professional.

Drugs on the horizon


Each year new therapies are gaining more ground in treating and possibly curing HIV.
For instance researchers are investigating nanosuspensions of antiretroviralsTrusted Source for both HIV treatment and prevention. These medications would be taken every 4 to 8 weeks. They could improve adherence by reducing 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” designationTrusted Source from the FDA which will speed up the drug development process.
A monthly injection that combines rilpivirine with the an INSTI cabotegravir is scheduled to become available for treatment of HIV-1 infection in early 2020. HIV-1 is the most common type of HIV virus.
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 professional 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.

Types of antiretroviral drugs


Treatments that are commonly prescribed to people beginning antiretroviral therapy can be divided into five classes:
nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs)integrase strand transfer inhibitors (INSTIs)protease inhibitors (PIs)non-nucleoside reverse transcriptase inhibitors (NNRTIs)entry inhibitors
The drugs listed below have all been approved by the Food and Drug Administration (FDA) to treat HIV.
Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs)
NRTIs keep cells containing HIV from making copies of themselves by interrupting the reconstruction of the virus’s DNA chain when it uses the enzyme reverse transcriptase. NRTIs include:
abacavir (available as the stand-alone drug Ziagen or as a part of three different combination drugs)lamivudine (available as the stand-alone drug Epivir or as a part of nine different combination drugs)emtricitabine (available as the stand-alone drug Emtriva or as a part of nine different combination drugs)zidovudine (available as the stand-alone drug Retrovir or as a part of two different combination drugs)tenofovir disoproxil fumarate (available as the stand-alone drug Viread or as a part of nine different combination drugs)tenofovir alafenamide fumarate (available as the stand-alone drug Vemlidy or as a part of five different combination drugs)
Zidovudine is also known as azidothymidine or AZT and it was the first drug approved by the FDA to treat HIV. These days it’s more likely to be used as post-exposure prophylaxis (PEP) for newborns with HIV-positive mothers than as a treatment for HIV-positive adults.
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. Other NRTIs (emtricitabine lamivudine and tenofovir disoproxil fumarate) may also be used to treat hepatitis B.
Combination NRTIs include:
abacavir lamivudine and zidovudine (Trizivir)abacavir and lamivudine (Epzicom)lamivudine and zidovudine (Combivir)lamivudine and tenofovir disoproxil fumarate (Cimduo Temixys)emtricitabine and tenofovir disoproxil fumarate (Truvada)emtricitabine and tenofovir alafenamide fumarate (Descovy)
In addition to being used to treat HIV Descovy and Truvada may also be used as part of a pre-exposure prophylaxis (PrEP) regimen.
As of 2019 the U.S. Preventive Services Task Force recommends a PrEP regimen for all people without HIV who are at increased risk of contracting HIV.
Integrase strand transfer inhibitors (INSTIs)
INSTIs disable integrase an enzyme that HIV uses to put HIV DNA into human DNA inside the CD4 T cells. INSTIs belong to a category of drugs known as integrase inhibitors.
INSTIs are well-established drugs. The other categories of integrase inhibitors such as integrase binding inhibitors (INBIs) are considered experimental drugs. INBIs haven’t received FDA approval.
INSTIs include:
raltegravir (Isentress Isentress HD)dolutegravir (available as the stand-alone drug Tivicay or as a part of three different combination drugs)bictegravir (combined with emtricitabine and tenofovir alafenamide fumarate in the drug Biktarvy)elvitegravir (combined with cobicistat emtricitabine and tenofovir alafenamide fumarate in the drug Genvoya or with cobicistat emtricitabine and tenofovir disoproxil fumarate in the drug Stribild)
Protease inhibitors (PIs)
PIs disable protease an enzyme that HIV needs as part of its life cycle. PIs include:
atazanavir (available as the stand-alone drug Reyataz or combined with cobicistat in the drug Evotaz)darunavir (available as the stand-alone drug Prezista or as a part of two different combination drugs)fosamprenavir (Lexiva)indinavir (Crixivan)lopinavir (only available when combined with ritonavir in the drug Kaletra)nelfinavir (Viracept)ritonavir (available as the stand-alone drug Norvir or combined with lopinavir in the drug Kaletra)saquinavir (Invirase)tipranavir (Aptivus)
Ritonavir (Norvir) is often used as a booster drug for other antiretroviral medications.
Due to their side effects indinavir nelfinavir and saquinavir are rarely used.
Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
Non-nucleoside reverse transcriptase inhibitors (NNRTIs) prevent HIV from making copies of itself by binding to and stopping the enzyme reverse transcriptase. NNRTIs include:
efavirenz (available as the stand-alone drug Sustiva or as a part of three different combination drugs)rilpivirine (available as the stand-alone drug Edurant or as a part of three different combination drugs)etravirine (Intelence)doravirine (available as the stand-alone drug Pifeltro or combined with lamivudine and tenofovir disoproxil fumarate in the drug Delstrigo)nevirapine (Viramune Viramune XR)
Entry inhibitors
Entry inhibitors are a class of drugs that block HIV from entering CD4 T cells. These inhibitors include:
enfuvirtide (Fuzeon) which belongs to the drug class known as fusion inhibitorsmaraviroc (Selzentry) which belongs to the drug class known as chemokine coreceptor antagonists (CCR5 antagonists)ibalizumab-uiyk (Trogarzo) which belongs to the drug class known as post-attachment inhibitors
Entry inhibitors are rarely used as first-line treatments.

How HIV drugs work


The main treatment for HIV today is antiretroviral medications. These medications 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.
 


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