Antiretroviral is a drug used to prevent a retrovirus, such as HIV, from replicating. The term antiretroviral primarily refers to antiretroviral HIV drugs. Treatment with HIV medicines is called antiretroviral therapy. The goal of HIV therapy drugs is to prevent HIV from multiplying. Antiretroviral therapy is recommended for everyone with HIV, and people with HIV should start antiretroviral therapy as soon as possible. People on antiretroviral therapy take a combination of HIV medicines called an HIV treatment regimen every day. There are six classes of drugs used in antiretroviral therapy. These drugs are generally classified by the phase of the HIV life cycle inhibited by them 1. A person’s initial HIV regimen generally includes three HIV medicines from at least two different HIV drug classes. More common combinations include two nucleoside reverse transcriptase inhibitors (NRTIs) and one non-nucleoside reverse transcriptase inhibitor (NNRTI), protease inhibitor (PI), or integrase inhibitor (II). The drugs are listed below according to their class and generic names.
People who are exposed to HIV-positive infectious bodily fluids either by skin puncture, damaged skin, or direct mucous membrane contact are at risk for transmission and should start antiretroviral therapy as soon as possible. The United States Public Health Service guidelines recommend starting prophylactics up to 72 hours post exposure 1. The recommended regimen is emtricitabine plus tenofovir plus raltegravir for 4 weeks. Those who are exposed to HIV should have follow-up HIV testing at 6, 12, and 24 weeks. If the test results are negative at 24 weeks, they are considered uninfectious 2.
A recent HIV Infection is one that occurs up to 6 months after infection. An HIV regimen often varies based on potential drug interactions with the patient’s current medications and the adverse effects experienced.
Patients who are pregnant should begin treatment immediately to prevent mother-to-child transmission of HIV and protect the health of the woman 3.
There are five major types of antiretroviral medications:
- Reverse transcriptase inhibitors – interfere with a critical step during the HIV life cycle and keep the virus from making copies of itself
- Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
- Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
- Protease inhibitors – interfere with a protein that HIV uses to make infectious viral particles
- Fusion inhibitors – block the virus from entering the body’s cells
- Integrase inhibitors – block an enzyme HIV needs to make copies of itself
- Multidrug combinations – combine two or more different types of drugs into one
The following includes all FDA-approved HIV medications:
- Nucleoside Reverse Transcriptase Inhibitors (NRTIs): Abacavir, emtricitabine, lamivudine; Tenofovir disoproxil fumarate, zidovudine
- Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs): Efavirenz, etravirine, nevirapine, rilpivirine
- Fusion inhibitors (FIs): Enfuvirtide
- Protease inhibitors (PIs): Atazanavir, darunavir, fosamprenavir, ritonavir, saquinavir, tipranavir
- CCR5 Antagonist: Maraviroc
- Integrase inhibitors: Dolutegavir, raltegravir, elritegnavir, bivtogravir
- Post-Attachment Inhibitors: Ibalizumab
- Pharmacokinetic Enhancers: Cobicistat
The following includes all FDA-approved HIV combination medicines:
- Abacavir and lamivudine
- Abacavir, dolutegravir, and lamivudine
- Abacavir, lamivudine, and zidovudine
- Atazanavir and cobicistat
- Bictegravir, emtricitabine, and tenofovir alafenamide
- Darunavir and cobicistat
- Dolutegravir and rilpivirine
- Efavirenz, emtricitabine, and tenofovir disoproxil fumarate
- Efavirenz, lamivudine, and tenofovir disoproxil fumarate
- Efavirenz, lamivudine, and tenofovir disoproxil fumarate
- Elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide fumarate
- Elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate
- Emtricitabine, rilpivirine, and tenofovir alafenamide
- Emtricitabine, rilpivirine, and tenofovir disoproxil fumarate
- Emtricitabine and tenofovir alafenamide
- Emtricitabine and tenofovir disoproxil fumarate
- Lamivudine and tenofovir disoproxil fumarate
- Lamivudine and zidovudine
- Lopinavir and ritonavir
The FDA does not approve investigational HIV drugs. Investigational drugs include those used to treat or prevent HIV and vaccines to treat or prevent HIV. These drugs are only offered in clinical trials. No vaccines exist yet; however, researchers are studying this possibility 4.
The following table lists HIV medicines recommended for the treatment of HIV infection in the United States based on the U.S. Department of Health and Human Services HIV/AIDS medical practice guidelines. All of these drugs are approved by the U.S. Food and Drug Administration (FDA). The HIV medicines are listed according to drug class and identified by generic and brand names.
These antiretroviral drugs help people with HIV, but they are not perfect. Antiretroviral drugs do not cure HIV/AIDS. People with HIV infection still have the virus in their bodies. They can still spread HIV to others through unprotected sex and needle sharing, even when they are taking their antiretroviral drugs.
Table 1. FDA-Approved HIV Medicines
| Drug Class | Generic Name (Other names and acronyms) | Brand Name |
| Nucleoside Reverse Transcriptase Inhibitors (NRTIs) | ||
| NRTIs block reverse transcriptase, an enzyme HIV needs to make copies of itself. | abacavir (abacavir sulfate, ABC) | Ziagen |
| emtricitabine (FTC) | Emtriva | |
| lamivudine (3TC) | Epivir | |
| tenofovir disoproxil fumarate (tenofovir DF, TDF) | Viread | |
| zidovudine (azidothymidine, AZT, ZDV) | Retrovir | |
| Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) | ||
| NNRTIs bind to and later alter reverse transcriptase, an enzyme HIV needs to make copies of itself. | doravirine (DOR) | Pifeltro |
| efavirenz (EFV) | Sustiva | |
| etravirine (ETR) | Intelence | |
| nevirapine (extended-release nevirapine, NVP) | Viramune | |
| Viramune XR (extended release) | ||
| rilpivirine (rilpivirine hydrochloride, RPV) | Edurant | |
| Protease Inhibitors (PIs) | ||
| Protease Inhibitors block HIV protease, an enzyme HIV needs to make copies of itself. | atazanavir (atazanavir sulfate, ATV) | Reyataz |
| darunavir (darunavir ethanolate, DRV) | Prezista | |
| fosamprenavir (fosamprenavir calcium, FOS-APV, FPV) | Lexiva | |
| ritonavir (RTV) *Although ritonavir is a protease inhibitor, it is generally used as a pharmacokinetic enhancer as recommended in the Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV and the Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection. | Norvir | |
| saquinavir (saquinavir mesylate, SQV) | Invirase | |
| tipranavir (TPV) | Aptivus | |
| Fusion Inhibitors | ||
| Fusion inhibitors block HIV from entering the CD4 cells of the immune system. | enfuvirtide (T-20) | Fuzeon |
| CCR5 Antagonists | ||
| CCR5 antagonists block CCR5 coreceptors on the surface of certain immune cells that HIV needs to enter the cells. | maraviroc (MVC) | Selzentry |
| Integrase Inhibitors | ||
| Integrase inhibitors block HIV integrase, an enzyme HIV needs to make copies of itself. | dolutegravir (DTG, dolutegravir sodium) | Tivicay |
| raltegravir (raltegravir potassium, RAL) | Isentress | |
| Isentress HD | ||
| Post-Attachment Inhibitors | ||
| Post-attachment inhibitors block CD4 receptors on the surface of certain immune cells that HIV needs to enter the cells. | ibalizumab-uiyk (Hu5A8, IBA, Ibalizumab, TMB-355, TNX-355) | Trogarzo |
| Pharmacokinetic Enhancers | ||
| Pharmacokinetic enhancers are used in HIV treatment to increase the effectiveness of an HIV medicine included in an HIV regimen. | cobicistat (COBI, c) | Tybost |
| Combination HIV Medicines | ||
| Combination HIV medicines contain two or more HIV medicines from one or more drug classes. | abacavir and lamivudine (abacavir sulfate / lamivudine, ABC / 3TC) | Epzicom |
| abacavir, dolutegravir, and lamivudine (abacavir sulfate / dolutegravir sodium / lamivudine, ABC / DTG / 3TC) | Triumeq | |
| abacavir, lamivudine, and zidovudine (abacavir sulfate / lamivudine / zidovudine, ABC / 3TC / ZDV) | Trizivir | |
| atazanavir and cobicistat (atazanavir sulfate / cobicistat, ATV / COBI) | Evotaz | |
| bictegravir, emtricitabine, and tenofovir alafenamide (bictegravir sodium / emtricitabine / tenofovir alafenamide fumarate, BIC / FTC / TAF) | Biktarvy | |
| darunavir and cobicistat (darunavir ethanolate / cobicistat, DRV / COBI) | Prezcobix | |
| darunavir, cobicistat, emtricitabine, and tenofovir alafenamide (darunavir ethanolate / cobicistat / emtricitabine / tenofovir AF, darunavir ethanolate / cobicistat / emtricitabine / tenofovir alafenamide, darunavir / cobicistat / emtricitabine / tenofovir AF, darunavir / cobicistat / emtricitabine / tenofovir alafenamide fumarate, DRV / COBI / FTC / TAF) | Symtuza | |
| dolutegravir and lamivudine (dolutegravir sodium / lamivudine, DTG / 3TC) | Dovato | |
| dolutegravir and rilpivirine (dolutegravir sodium / rilpivirine hydrochloride, DTG / RPV) | Juluca | |
| doravirine, lamivudine, and tenofovir disoproxil fumarate (doravirine / lamivudine / TDF, doravirine / lamivudine / tenofovir DF, DOR / 3TC / TDF) | Delstrigo | |
| efavirenz, emtricitabine, and tenofovir disoproxil fumarate (efavirenz / emtricitabine / tenofovir DF, EFV / FTC / TDF) | Atripla | |
| efavirenz, lamivudine, and tenofovir disoproxil fumarate (EFV / 3TC / TDF) | Symfi | |
| efavirenz, lamivudine, and tenofovir disoproxil fumarate (EFV / 3TC / TDF) | Symfi Lo | |
| elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide (elvitegravir / cobicistat / emtricitabine / tenofovir alafenamide fumarate, EVG / COBI / FTC / TAF) | Genvoya | |
| elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate (QUAD, EVG / COBI / FTC / TDF) | Stribild | |
| emtricitabine, rilpivirine, and tenofovir alafenamide (emtricitabine / rilpivirine / tenofovir AF, emtricitabine / rilpivirine / tenofovir alafenamide fumarate, emtricitabine / rilpivirine hydrochloride / tenofovir AF, emtricitabine / rilpivirine hydrochloride / tenofovir alafenamide, emtricitabine / rilpivirine hydrochloride / tenofovir alafenamide fumarate, FTC / RPV / TAF) | Odefsey | |
| emtricitabine, rilpivirine, and tenofovir disoproxil fumarate (emtricitabine / rilpivirine hydrochloride / tenofovir disoproxil fumarate, emtricitabine / rilpivirine / tenofovir, FTC / RPV / TDF) | Complera | |
| emtricitabine and tenofovir alafenamide (emtricitabine / tenofovir AF, emtricitabine / tenofovir alafenamide fumarate, FTC / TAF) | Descovy | |
| emtricitabine and tenofovir disoproxil fumarate (emtricitabine / tenofovir DF, FTC / TDF) | Truvada | |
| lamivudine and tenofovir disoproxil fumarate (Temixys, 3TC / TDF) | Cimduo | |
| lamivudine and zidovudine (3TC / ZDV) | Combivir | |
| lopinavir and ritonavir (ritonavir-boosted lopinavir, LPV/r, LPV / RTV) | Kaletra | |
Nucleoside Reverse Transcriptase Inhibitor (NRTI)
Nucleoside reverse transcriptase inhibitors (NRTIs) block reverse transcriptase an HIV enzyme. HIV uses reverse transcriptase to convert its RNA into DNA (reverse transcription). Blocking reverse transcriptase and reverse transcription prevents HIV from replicating.
Nucleoside reverse transcriptase inhibitors compete with natural deoxynucleotides for incorporation into a growing viral DNA chain. However, nucleoside reverse transcriptase inhibitors lack a 3′-hydroxyl group on the deoxyribose moiety. This results in incorporation of an nucleoside reverse transcriptase inhibitor and the next incoming deoxynucleotide cannot form the next 5′, 3′ phosphodiester bond needed to extend the DNA chain. The result is a chain termination in DNA synthesis.
Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
Non-nucleoside reverse transcriptase inhibitors (NNRTIs) bind to and block HIV reverse transcriptase by directly binding to the HIV enzyme. HIV uses reverse transcriptase to convert its RNA into DNA (reverse transcription). Blocking reverse transcriptase and reverse transcription prevents HIV from replicating. Though non-nucleoside reverse transcriptase inhibitors are not incorporated into the viral DNA, they inhibit movement of protein domains of reverse transcriptase that are essential to carry out the DNA synthesis.
Protease Inhibitors (PIs)
Protease inhibitors (PIs) bind and block HIV-1 protease. By blocking protease, protease inhibitors (PIs) prevent new (immature) HIV from becoming a mature virus that can infect other CD4 cells.
Fusion Inhibitors
Fusion inhibitors block the HIV envelope from merging with the host CD4 cell membrane (fusion). This prevents HIV from entering the CD4 cell. Fusion inhibitors disrupt binding, fusion, and entry of HIV virions into a human cell. Enfuvirtide binds to gp41 and disrupts membrane attachment.
CCR5 Antagonist
CCR5 antagonist Maraviroc blocks the CCR5 coreceptor on the CD4 T lymphocytes (CD4 cells) to prevent viral attachment. This prevents HIV from entering the cell.
Integrase Inhibitors
Integrase inhibitors also called integrase strand transfer inhibitors, block the action of integrase (an HIV enzyme), preventing the viral DNA from inserting itself into the DNA of a host CD4 cell. Blocking integrase prevents HIV from replicating.
Post-Attachment Inhibitors
Post-attachment inhibitors are a class of drugs that bind to the CD4 receptor on a host CD4 cell inhibiting viral entry into the cell. This blocks HIV from attaching to the CCR5 and CXCR4 coreceptors and entering the cell. Post-attachment inhibitors are part of a larger group of HIV drugs called entry inhibitors.
Pharmacokinetic Enhancers
Pharmacokinetic enhancers inhibit human CYP3A protein, increasing plasma concentration of other anti-HIV drugs. When the two drugs are given together, the pharmacokinetic enhancer interferes with the breakdown of the other drug, which allows the drug to remain in the body longer at a higher concentration. Pharmacokinetic enhancers are included in some HIV treatment regimens.
Nucleoside reverse transcriptase inhibitors (NRTIs) side effects
Hypersensitivity reaction or rash, neutropenia, myopathy, anemia, neuropathy, mitochondrial toxicity, lactic acid build up, pancreatitis, fever, rash, nausea, vomiting, diarrhea, abdominal pain, fatigue, achiness, shortness of breath, sore throat, dark-colored urine, lipoatrophy, and jaundice 5.
Non-nucleoside reverse transcriptase inhibitors (NNRTIs) side effects
Severe rash, allergic reactions, depression, impaired concentration, headache, sleep disturbance, abnormal dreams, mood changes, jaundice, dark-colored urine, fatigue, nausea and vomiting, peripheral neuropathy, mouth sores, conjunctivitis, myopathy, blisters, and trouble breathing.
Protease Inhibitors side effects
Irregular heart rhythm, lipohypertrophy, severe rash, jaundice, dizziness, lightheadedness, heartburn, fatigue, myopathy, conjunctivitis, mouth sores, mouth numbness, kidney stones, blisters, dark-colored urine, pancreatitis, painful swelling, and abdominal pain.
Fusion Inhibitors side effects
Injection site reactions, infection, trouble breathing, fever, blood in urine, dark- colored urine, low blood pressure, neutropenia, chills and shivering, and cough.
CCR5 Antagonist side effects
Allergic reaction, jaundice, dark-colored urine, vomiting, abdominal pain, fever, fatigue, myopathy, mouth and skin blisters, facial swelling, trouble breathing, upper respiratory tract infections, cough, joint pain, myopathy, pain below ribs, heart problems, and loss of appetite.
Integrase Inhibitors side effects
Allergic hypersensitivity reaction, rash, jaundice, dark-colored urine, pale bowel movements, diarrhea, flatulence, nausea and vomiting, loss of appetite, abnormal dreams, pruritus, pain below ribs, mouth and skin blisters, and fatigue.
Post-Attachment Inhibitors side effects
Immune reconstitution inflammatory syndrome
Pharmacokinetic Enhancers side effects
Increased serum creatinine, proteinuria, nausea, diarrhea, headache, and acute kidney injury and kidney failure.
Some long-term adverse effects that may occur from HIV medicines are hepatotoxicity, kidney failure, heart disease, diabetes/insulin resistance, hyperlipidemia, osteoporosis, suicidal ideation/depression, and nervous system deficits 6.
- Abacavir: Patients who have the HLA-B*5701 allele, or with a prior hypersensitivity reaction to abacavir or with moderate or severe hepatic impairment 7
- Emtricitabine: Patients with previously demonstrated hypersensitivity to any of the components of the products
- Lamivudine: Patients with a previous hypersensitivity reaction to lamivudine
- Tenofovir Disoproxil Fumarate: Previous hypersensitivity and/or glomerular filtration rate (GFR) less than 50
- Zidovudine: Patients who have had potentially life-threatening allergic reactions (e.g., anaphylaxis, Stevens-Johnson syndrome) to any of the components of the formulations
- Efavirenz: Patients with clinically significant hypersensitivity, for example, Stevens-Johnson syndrome, erythema multiforme, or toxic skin eruptions) to any of the ingredients of this product. Coadministration of efavirenz with elbasvir and grazoprevir is contraindicated.
- Etravirine: Hypersensitivity
- Nevirapine: In patients with moderate or severe (Child-Pugh Class B or C, respectively) hepatic impairment or for use as occupational and non-occupational post-exposure prophylaxis (PEP) regimens. Women with CD4 greater than 250 or men with CD4 greater than 400 due to an increased probability of hypersensitivity reaction.
- Rilpivirine: Contraindicated for co-administration with all of the following; carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifampin, rifapentine, dexamethasone, St. John’s wort, esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole
- Atazanavir: In patients with previously demonstrated clinically significant hypersensitivity, for example, Stevens-Johnson syndrome, erythema multiforme, or toxic skin eruptions, to any of the ingredients of formulations. When co-administered with medications that are highly dependent on CYP3A or UGT1A1 for clearance, and for patients in which elevated plasma concentrations of the interacting drugs are associated with serious and life-threatening events. When co-administered with drugs that strongly induce CYP3A and may lead to lower exposure and loss of efficacy of formulations
- Darunavir: Co-administration of formulations is contraindicated with medications that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and life-threatening events
- Fosamprenavir: In patients with previously demonstrated clinically significant hypersensitivity, for example, Stevens-Johnson syndrome, to any of the components of this product or amprenavir. When co-administered with medications that are highly dependent on cytochrome P450 3A4 (CYP3A4) for clearance and for which elevated plasma concentrations are associated with serious and life-threatening events
- Ritonavir: Contraindicated in patients with known hypersensitivity for example, toxic epidermal necrolysis (TEN), or Stevens-Johnson syndrome, to ritonavir or any of its ingredients. Ritonavir is contraindicated with medications that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and life-threatening reactions. Also contraindicated with medications that are potent CYP3A inducers where significantly reduced lopinavir plasma concentrations may be associated with the potential for loss of virologic response and possible resistance and cross-resistance 8
- Saquinavir: Contraindicated in those with congenital long QT syndrome, those with refractory hypokalemia or hypomagnesemia, and in combination with drugs that both increase saquinavir plasma concentrations and prolong the QT interval. Is also contraindicated in people with complete atrioventricular (AV) block without implanted pacemakers, or in patients who are at high risk of complete AV block. Contraindicated in patients with clinically significant hypersensitivity (e.g., anaphylactic reaction, Stevens-Johnson syndrome) to saquinavir, saquinavir mesylate, or any of its ingredients. Contraindicated in patients with severe hepatic impairment. Is also contraindicated with drugs that are CYP3A substrates for which increased plasma levels may result in serious or life-threatening reactions.
- Tipranavir: Contraindicated in moderate to severe hepatic impairment and co-administration with drugs that are highly dependent on CYP 3A for clearance or are potent CYP 3A inducers. Increased risk of intracranial bleeding.
- Enfuvirtide: Known hypersensitivity to enfuvirtide or any of its components
- Maraviroc: Contraindicated in patients with severe renal impairment or ESRD (CrCl less than 30 mL per minute) who are concomitantly taking potent CYP3A inhibitors or inducers.
- Dolutegravir: With previous hypersensitivity reaction to dolutegravir or receiving dofetilide due to the potential for higher dofetilide plasma concentrations and the risk for serious and life-threatening events
- Raltegravir: None
- Ibalizumab: None
- Cobicistat: The concomitant use of cobicistat with atazanavir or darunavir and is contraindicated due to the potential for serious and/or life-threatening events or loss of therapeutic effect
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- O’Donovan K, Emeto TI. Mother-to-child transmission of HIV in Australia and other high-income countries: Trends in perinatal exposure, demography and uptake of prevention strategies. Aust N Z J Obstet Gynaecol. 2018 Oct;58(5):499-505
- Trovato M, D’Apice L, Prisco A, De Berardinis P. HIV Vaccination: A Roadmap among Advancements and Concerns. Int J Mol Sci. 2018 Apr 19;19, 4
- Guzman N, Al Aboud AM. StatPearls [Internet]. StatPearls Publishing; Treasure Island (FL): Oct 27, 2018. HIV-associated Lipodystrophy.
- Chawla A, Wang C, Patton C, Murray M, Punekar Y, de Ruiter A, Steinhart C. A Review of Long-Term Toxicity of Antiretroviral Treatment Regimens and Implications for an Aging Population. Infect Dis Ther. 2018 Jun;7(2):183-195
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