Table of ContentsView AllTable of ContentsBefore HAARTAdvent of HAARTFrom HAART to ARTART Today
Table of ContentsView All
View All
Table of Contents
Before HAART
Advent of HAART
From HAART to ART
ART Today
Antiretroviral therapy is used to treatHIVand is comprised of a combination of drugs that block different stages in thevirus' replication cycle. By doing so, the virus can be suppressed to undetectable levels where it can do the body little harm.
Justin Sullivan / Getty Images News / Getty Images
What Are Antiretrovirals and How Do They Work?
When the first cases of HIV were identified in the United States in 1982, scientists rushed to find ways to treat a virus that had little precedent in modern medicine.
The rapid development of drug resistance rendered the drug increasingly useless, while the drug’s toxic effects often left users with severeanemia, liver problems, and other intolerable complications.
Three other drugs were approved between 1991 and 1994—Hivid (ddC, zalcitabine), Videx (ddI, didanosine), and Zerit (d4T, stavudine)—and used in combination therapies in an effort to further extend life expectancy. And, while they certainly helped, they proved even more toxic than AZT and required complex dosing schedules, often with multiple doses taken throughout the day and night.
What researchers quickly began to realize is that these drugs—and subsequent ones like Viramune (nevirapine) and Epivir (3TC, lamivudine)—failed to achieve durable control because they all had similar mechanisms of action and only blocked one of the seven stages of HIV’s replication cycle.
In 1995, the FDA approved the first protease inhibitor, called Invirase (saquinavir).Unlike other antiretrovirals of the time, which blocked the virus' ability to “hijack” a cell’s genetic machinery and turn it into an HIV-producing factory, PIs blocked the virus' ability to assemble new copies of itself from structural proteins.
This one-two approach proved to be the turning point in the growingpandemic.
It was reported at the 1996 conference in Vancouver that the strategic use of three drugs from each of the two classes was able to achieve and sustain anundetectable viral load, effectively putting the disease into remission.
Even so, HAART was far from perfect, and the average life expectancy, while vastly improved, was still less than that of the general population. By the turn of the century, a 20-year-old on antiretroviral therapy could potentially live to their early 50s.
Within this context, “highly effective” was as indicative of HAART’s limitations as its benefits.
HIV Statistics You Should Know
Beyond HAART
By 2000, the limitations of the available antiretroviral drugs became increasingly clear. Despite their ability to achieve viral suppression, they could be extremely challenging to the user for several different reasons:
So problematic were these issues that HAART was standardly delayed until the immune function dropped below a certain threshold (namely, aCD4 countof less than 350). The risks of early treatment at the time were seen to outweigh the benefits.
All of that changed in 2001 with the introduction of Viread (tenofovir disoproxil fumarate), a new type of NRTI that had far fewer side effects, could overcome deep resistance, and only required one pill daily.
With universal treatment at diagnosis becoming the new standard worldwide, the medical community began using ART to describe a therapeutic approach that was now more than just “highly effective.”
HIV Facts and Statistics in the US and Abroad
The main difference between HAART of the late-1990s/early-2000s and ART today is that HIV can truly be considered a chronic, manageable condition. Not only can a 20-year-old diagnosed with HIV today live well into their 70s, but they can do so with drugs that are safer, longer-lasting, and easier to take.
Life Expectancy for People Living With HIV
Newer Drugs and Drug Classes
In recent years, newer classes of antiretroviral drugs have been developed to attack the virus in different ways. Some prevent the attachment of HIV to host cells (entry/attachment inhibitors), while others block the integration of viral coding into the host cell’s nucleus (integrase inhibitors).
In 2023, the FDA approved the first capsid inhibitor, Sunlenca (lenacapavir). Capsid inhibitors interfere with the HIV capsid, a protein shell that protects HIV’s genetic material and enzymes needed for replication.
In addition, newer versions of PIs, NRTIs, and NNRTIs have been created that offer better pharmacokinetics (drug activity), fewer side effects, and better drug resistance profiles.
Fixed-Dose Combination Drugs
Single-pill formulations not only improved adherence rates but have been shown to significantly reduce the risk of severe illnesses and hospitalizations compared to multi-pill antiretroviral therapies.
How to Know If You Have HIV
Redefining Combination Therapy
The term HAART has long been synonymous with triple-drug therapy. And, while it is true that ART typically consists of three or more antiretrovirals, improved pharmacokinetics have now made it possible to treat HIV with only two antiretroviral drugs.
In 2019, the FDA approved the first complete two-drug therapy, known as Dovato, which combines a newer-generation integrase inhibitor called dolutegravir with an older NRTI called lamivudine. The combination has proven to be just as effective as standard triple therapy with fewer side effects.
Further turning the definition of ART on its ear was the 2021 release of an injectable therapy known as Cabenuva.
Cabenuva is the firstonce-monthlytherapy able to achieve sustained viral suppression with one injection of the integrase inhibitor cabotegravir and one injection of a newer NNRTI called rilpivirine.It’s now approved to be given every other month.
Advances like these redefine what ART means and what it might eventually become.
List of Approved HIV Antiretroviral Drugs
A Word From Verywell
Although the goals of antiretroviral therapy remain the same, ART today bears only a glancing resemblance to HAART of the past. Without exception, the benefits of treatment far outweigh any concerns about the drugs or their side effects.
Moreover, the benefits extend to those who are not infected. Landmark research published in a 2019 edition ofTheLancetconcluded that people with HIV who achieve an undetectable viral load have azero chance of infecting others.
These factors further punctuate the need forHIV testingand illustrate why the U.S. Preventive Services Task Force recommends that all Americans ages 15 to 65 be tested for HIV once as part of a routine doctor’s visit.
What To Expect When Getting an HIV Test
19 SourcesVerywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.Vella S, Schwartlander B, Sow SP, Eholie SP, Murphy RL.The history of antiretroviral therapy and of its implementation in resource-limited areas of the world.AIDS. 26(10):1231-41. doi:10.1097/QAD.0b013e32835521a3GlaxoSmithKline.Package insert - Retrovir (zidovudine).Brady MT, Oleske JM, Williams PL, et al.Declines in mortality rates and changes in causes of death in HIV-1-infected children during the HAART era.J Acquir Immune Defic Syndr. 53(1):86-94. doi:10.1097/QAI.0b013e3181b9869fMarcus JL, Leyden WA, Alexeeff SE, et al.Comparison of overall and comorbidity-free life expectancy between insured adults with and without HIV infection, 2000-2016.JAMA Netw Open. 3(6):e207954. doi:10.1001/jamanetworkopen.2020.7954Margolis AM, Heverling H, Pham PA, Stolbach A.A review of the toxicity of HIV medications.J Med Toxicol.10(1):26-39. doi:10.1007/s13181-013-0325-8Melikian GL, Rhee SY, Varghese V, et al.Non-nucleoside reverse transcriptase inhibitor (NNRTI) cross-resistance: implications for preclinical evaluation of novel NNRTIs and clinical genotypic resistance testing.J Antimicrob Chemother.69(1):12-20. doi:10.1093/jac/dkt316Van Dyke RB, Ngo-Giang-Huang N, Shapiro DE, et al.A comparison of 3 regimens to prevent nevirapine resistance mutations in HIV-infected pregnant women receiving a single intrapartum dose of nevirapine.Clin Infect Dis.54(12):285-93. doi: 10.1093/cid/cir798U.S. Food and Drug Administration.HIV treatment information for adults.Villa G, Phillips RO, Smith C, et al.Drug resistance outcomes of long-term ART with tenofovir disoproxil fumarate in the absence of virological monitoring.J Antimicrob Chemother. 73(11):3148-57. doi:10.1093/jac/dky281The INSIGHT START Study Group.Initiation of antiretroviral therapy in early asymptomatic HIV infection.N Engl J Med.373:795-807. doi:10.1056/NEJMoa1506816Marcus JL, Chao CR, Leyden WA, et al.Narrowing the gap in life expectancy between HIV-infected and HIV-uninfected individuals with access to care.J Acquired Immune Def Synd. 73(1):39-46. doi:10.1097/QAI.0000000000001014Hill A, Hughes SL, Gotham D, Pozniak AL.Tenofovir alafenamide versus tenofovir disoproxil fumarate: Is there a true difference in efficacy and safety?J Virus Erad. 4(2): 72-9.U.S. Department of Health and Human Services.FDA-approved HIV medications.Scott SS, Hardin JW, Bramley TJ, D’Souza AO, Bennett CL.Single- versus multiple-tablet HIV regimens: adherence and hospitalization risks.Am J Manag Care. 22(4):242-8.U.S. Food and Drug Administration.FDA approves first two-drug complete regimen for HIV-infected patients who have never received antiretroviral treatment.U.S. Food and Drug Administration.FDA approves Cabenuva and Vocabria for the treatment of HIV-1 infection.GSKPro.com.Highlights of prescribing information: CABENUVA (cabotegravir extended-release injectable suspension; rilpivirine extended-release injectable suspension).Rodger A., Cambiano V, Bruun T, et al.Risk of HIV transmission through condomless sex in serodifferent gay couples with the HIV-positive partner taking suppressive antiretroviral therapy (PARTNER): final results of a multicentre, prospective, observational study.Lancet.pii: S0140-6736(19)30418-0. doi:10.1016/S0140-6736(19)30418-0.U.S. Preventive Services Task Force.Final draft recommendation: Human immunodeficiency virus (HIV) infection: Screening.
19 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.Vella S, Schwartlander B, Sow SP, Eholie SP, Murphy RL.The history of antiretroviral therapy and of its implementation in resource-limited areas of the world.AIDS. 26(10):1231-41. doi:10.1097/QAD.0b013e32835521a3GlaxoSmithKline.Package insert - Retrovir (zidovudine).Brady MT, Oleske JM, Williams PL, et al.Declines in mortality rates and changes in causes of death in HIV-1-infected children during the HAART era.J Acquir Immune Defic Syndr. 53(1):86-94. doi:10.1097/QAI.0b013e3181b9869fMarcus JL, Leyden WA, Alexeeff SE, et al.Comparison of overall and comorbidity-free life expectancy between insured adults with and without HIV infection, 2000-2016.JAMA Netw Open. 3(6):e207954. doi:10.1001/jamanetworkopen.2020.7954Margolis AM, Heverling H, Pham PA, Stolbach A.A review of the toxicity of HIV medications.J Med Toxicol.10(1):26-39. doi:10.1007/s13181-013-0325-8Melikian GL, Rhee SY, Varghese V, et al.Non-nucleoside reverse transcriptase inhibitor (NNRTI) cross-resistance: implications for preclinical evaluation of novel NNRTIs and clinical genotypic resistance testing.J Antimicrob Chemother.69(1):12-20. doi:10.1093/jac/dkt316Van Dyke RB, Ngo-Giang-Huang N, Shapiro DE, et al.A comparison of 3 regimens to prevent nevirapine resistance mutations in HIV-infected pregnant women receiving a single intrapartum dose of nevirapine.Clin Infect Dis.54(12):285-93. doi: 10.1093/cid/cir798U.S. Food and Drug Administration.HIV treatment information for adults.Villa G, Phillips RO, Smith C, et al.Drug resistance outcomes of long-term ART with tenofovir disoproxil fumarate in the absence of virological monitoring.J Antimicrob Chemother. 73(11):3148-57. doi:10.1093/jac/dky281The INSIGHT START Study Group.Initiation of antiretroviral therapy in early asymptomatic HIV infection.N Engl J Med.373:795-807. doi:10.1056/NEJMoa1506816Marcus JL, Chao CR, Leyden WA, et al.Narrowing the gap in life expectancy between HIV-infected and HIV-uninfected individuals with access to care.J Acquired Immune Def Synd. 73(1):39-46. doi:10.1097/QAI.0000000000001014Hill A, Hughes SL, Gotham D, Pozniak AL.Tenofovir alafenamide versus tenofovir disoproxil fumarate: Is there a true difference in efficacy and safety?J Virus Erad. 4(2): 72-9.U.S. Department of Health and Human Services.FDA-approved HIV medications.Scott SS, Hardin JW, Bramley TJ, D’Souza AO, Bennett CL.Single- versus multiple-tablet HIV regimens: adherence and hospitalization risks.Am J Manag Care. 22(4):242-8.U.S. Food and Drug Administration.FDA approves first two-drug complete regimen for HIV-infected patients who have never received antiretroviral treatment.U.S. Food and Drug Administration.FDA approves Cabenuva and Vocabria for the treatment of HIV-1 infection.GSKPro.com.Highlights of prescribing information: CABENUVA (cabotegravir extended-release injectable suspension; rilpivirine extended-release injectable suspension).Rodger A., Cambiano V, Bruun T, et al.Risk of HIV transmission through condomless sex in serodifferent gay couples with the HIV-positive partner taking suppressive antiretroviral therapy (PARTNER): final results of a multicentre, prospective, observational study.Lancet.pii: S0140-6736(19)30418-0. doi:10.1016/S0140-6736(19)30418-0.U.S. Preventive Services Task Force.Final draft recommendation: Human immunodeficiency virus (HIV) infection: Screening.
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
Vella S, Schwartlander B, Sow SP, Eholie SP, Murphy RL.The history of antiretroviral therapy and of its implementation in resource-limited areas of the world.AIDS. 26(10):1231-41. doi:10.1097/QAD.0b013e32835521a3GlaxoSmithKline.Package insert - Retrovir (zidovudine).Brady MT, Oleske JM, Williams PL, et al.Declines in mortality rates and changes in causes of death in HIV-1-infected children during the HAART era.J Acquir Immune Defic Syndr. 53(1):86-94. doi:10.1097/QAI.0b013e3181b9869fMarcus JL, Leyden WA, Alexeeff SE, et al.Comparison of overall and comorbidity-free life expectancy between insured adults with and without HIV infection, 2000-2016.JAMA Netw Open. 3(6):e207954. doi:10.1001/jamanetworkopen.2020.7954Margolis AM, Heverling H, Pham PA, Stolbach A.A review of the toxicity of HIV medications.J Med Toxicol.10(1):26-39. doi:10.1007/s13181-013-0325-8Melikian GL, Rhee SY, Varghese V, et al.Non-nucleoside reverse transcriptase inhibitor (NNRTI) cross-resistance: implications for preclinical evaluation of novel NNRTIs and clinical genotypic resistance testing.J Antimicrob Chemother.69(1):12-20. doi:10.1093/jac/dkt316Van Dyke RB, Ngo-Giang-Huang N, Shapiro DE, et al.A comparison of 3 regimens to prevent nevirapine resistance mutations in HIV-infected pregnant women receiving a single intrapartum dose of nevirapine.Clin Infect Dis.54(12):285-93. doi: 10.1093/cid/cir798U.S. Food and Drug Administration.HIV treatment information for adults.Villa G, Phillips RO, Smith C, et al.Drug resistance outcomes of long-term ART with tenofovir disoproxil fumarate in the absence of virological monitoring.J Antimicrob Chemother. 73(11):3148-57. doi:10.1093/jac/dky281The INSIGHT START Study Group.Initiation of antiretroviral therapy in early asymptomatic HIV infection.N Engl J Med.373:795-807. doi:10.1056/NEJMoa1506816Marcus JL, Chao CR, Leyden WA, et al.Narrowing the gap in life expectancy between HIV-infected and HIV-uninfected individuals with access to care.J Acquired Immune Def Synd. 73(1):39-46. doi:10.1097/QAI.0000000000001014Hill A, Hughes SL, Gotham D, Pozniak AL.Tenofovir alafenamide versus tenofovir disoproxil fumarate: Is there a true difference in efficacy and safety?J Virus Erad. 4(2): 72-9.U.S. Department of Health and Human Services.FDA-approved HIV medications.Scott SS, Hardin JW, Bramley TJ, D’Souza AO, Bennett CL.Single- versus multiple-tablet HIV regimens: adherence and hospitalization risks.Am J Manag Care. 22(4):242-8.U.S. Food and Drug Administration.FDA approves first two-drug complete regimen for HIV-infected patients who have never received antiretroviral treatment.U.S. Food and Drug Administration.FDA approves Cabenuva and Vocabria for the treatment of HIV-1 infection.GSKPro.com.Highlights of prescribing information: CABENUVA (cabotegravir extended-release injectable suspension; rilpivirine extended-release injectable suspension).Rodger A., Cambiano V, Bruun T, et al.Risk of HIV transmission through condomless sex in serodifferent gay couples with the HIV-positive partner taking suppressive antiretroviral therapy (PARTNER): final results of a multicentre, prospective, observational study.Lancet.pii: S0140-6736(19)30418-0. doi:10.1016/S0140-6736(19)30418-0.U.S. Preventive Services Task Force.Final draft recommendation: Human immunodeficiency virus (HIV) infection: Screening.
Vella S, Schwartlander B, Sow SP, Eholie SP, Murphy RL.The history of antiretroviral therapy and of its implementation in resource-limited areas of the world.AIDS. 26(10):1231-41. doi:10.1097/QAD.0b013e32835521a3
GlaxoSmithKline.Package insert - Retrovir (zidovudine).
Brady MT, Oleske JM, Williams PL, et al.Declines in mortality rates and changes in causes of death in HIV-1-infected children during the HAART era.J Acquir Immune Defic Syndr. 53(1):86-94. doi:10.1097/QAI.0b013e3181b9869f
Marcus JL, Leyden WA, Alexeeff SE, et al.Comparison of overall and comorbidity-free life expectancy between insured adults with and without HIV infection, 2000-2016.JAMA Netw Open. 3(6):e207954. doi:10.1001/jamanetworkopen.2020.7954
Margolis AM, Heverling H, Pham PA, Stolbach A.A review of the toxicity of HIV medications.J Med Toxicol.10(1):26-39. doi:10.1007/s13181-013-0325-8
Melikian GL, Rhee SY, Varghese V, et al.Non-nucleoside reverse transcriptase inhibitor (NNRTI) cross-resistance: implications for preclinical evaluation of novel NNRTIs and clinical genotypic resistance testing.J Antimicrob Chemother.69(1):12-20. doi:10.1093/jac/dkt316
Van Dyke RB, Ngo-Giang-Huang N, Shapiro DE, et al.A comparison of 3 regimens to prevent nevirapine resistance mutations in HIV-infected pregnant women receiving a single intrapartum dose of nevirapine.Clin Infect Dis.54(12):285-93. doi: 10.1093/cid/cir798
U.S. Food and Drug Administration.HIV treatment information for adults.
Villa G, Phillips RO, Smith C, et al.Drug resistance outcomes of long-term ART with tenofovir disoproxil fumarate in the absence of virological monitoring.J Antimicrob Chemother. 73(11):3148-57. doi:10.1093/jac/dky281
The INSIGHT START Study Group.Initiation of antiretroviral therapy in early asymptomatic HIV infection.N Engl J Med.373:795-807. doi:10.1056/NEJMoa1506816
Marcus JL, Chao CR, Leyden WA, et al.Narrowing the gap in life expectancy between HIV-infected and HIV-uninfected individuals with access to care.J Acquired Immune Def Synd. 73(1):39-46. doi:10.1097/QAI.0000000000001014
Hill A, Hughes SL, Gotham D, Pozniak AL.Tenofovir alafenamide versus tenofovir disoproxil fumarate: Is there a true difference in efficacy and safety?J Virus Erad. 4(2): 72-9.
U.S. Department of Health and Human Services.FDA-approved HIV medications.
Scott SS, Hardin JW, Bramley TJ, D’Souza AO, Bennett CL.Single- versus multiple-tablet HIV regimens: adherence and hospitalization risks.Am J Manag Care. 22(4):242-8.
U.S. Food and Drug Administration.FDA approves first two-drug complete regimen for HIV-infected patients who have never received antiretroviral treatment.
U.S. Food and Drug Administration.FDA approves Cabenuva and Vocabria for the treatment of HIV-1 infection.
GSKPro.com.Highlights of prescribing information: CABENUVA (cabotegravir extended-release injectable suspension; rilpivirine extended-release injectable suspension).
Rodger A., Cambiano V, Bruun T, et al.Risk of HIV transmission through condomless sex in serodifferent gay couples with the HIV-positive partner taking suppressive antiretroviral therapy (PARTNER): final results of a multicentre, prospective, observational study.Lancet.pii: S0140-6736(19)30418-0. doi:10.1016/S0140-6736(19)30418-0.
U.S. Preventive Services Task Force.Final draft recommendation: Human immunodeficiency virus (HIV) infection: Screening.
Meet Our Medical Expert Board
Share Feedback
Was this page helpful?Thanks for your feedback!What is your feedback?OtherHelpfulReport an ErrorSubmit
Was this page helpful?
Thanks for your feedback!
What is your feedback?OtherHelpfulReport an ErrorSubmit
What is your feedback?
