What drugs treat HIV/AIDS?
Though the original HIV/AIDS pandemic that started in the 1980s killed millions, multiple drugs regimens have since made HIV (human immunodeficiency virus) a chronic illness rather than an immediately terminal one.
HIV/AIDS is an incurable disease primarily transmitted through sexual contact. HIV attacks the body by harnessing its cells to produce more copies of the virus. Once the amount of virus reaches a certain level, it overwhelms the immune system, leading to full-blown AIDS (acquired immunodeficiency syndrome). In this condition, the infected person typically dies from one of a variety of opportunistic infections or cancers that attack their nearly defenseless body.
Antiretroviral drugs, the main category of drugs used for treatment of HIV, can block the virus from reproducing itself through targeting different chemicals the virus needs to make copies or perform other functions necessary its life cycle. The drug families used to treat HIV are classified based on what part of the virus’ reproductive process they target.
Nucleoside and nucleotide analogue reverse transcriptase inhibitors (NRTIs), for example, block reverse transcriptase. This is an enzyme the virus needs to infect white blood cells. Less reverse transcriptase means fewer newly infected cells. Protease inhibitors, on the other hand, block protease. Protease is crucial for HIV to make copies of itself, so less protease means the virus’ ability to colonize more cells is diminished. These and other drugs are prescribed in combination to attack the virus from various angles, which ideally leads to a more effective treatment with less drug resistance than single-drug treatment.
The ultimate goal of treatment is getting the viral load (the number of copies of the HIV in a person’s body) down below detectable levels. Periodic blood testing is an important part of therapy; as long as those viral load and antibody levels are below a proscribed range, people with HIV can stave off AIDS and other serious symptoms. This therapy also offers some protection to the infected person’s sex partner or partners.
People with HIV should note, however, that even when their infections are undetectable through lab tests, the viral load will rebound if they quit therapy or start missing doses. Some infections may also develop resistance to a particular drug cocktail, forcing treatment teams to come up with new regimens to beat back the resurgence of virus in the body.
The following are the different drug types currently used in treatment regimens for HIV:
- nucleoside and nucleotide analogue reverse transcriptase inhibitors (NRTIs)
- nonnucleoside analogue reverse transcriptase inhibitors (NNRTIs)
- protease inhibitors
- fusion inhibitors
- CCR5 antagonists
- integrase strand transfer inhibitors, and
- entry inhibitors
Antiviral treatment options have primarily included combinations of two NRTIs, often referred to as "nucs," and a third drug, typically being a boosted protease inhibitor, a NNRTI, often called "non-nucs," and integrase strand transfer inhibitors such as RAL, EVG, DTG, or BIC. Many of these drugs are available in fixed-dose combinations as well as increasing numbers of drugs as single-tablet regimens.
This article will describe each family of drugs currently available for standard treatment and control of HIV infections.
What are nucleoside and nucleotide analogue reverse transcriptase inhibitors (NRTIs)?
NRTIs block an enzyme of the human immunodeficiency virus called reverse transcriptase that allows HIV to infect human cells, particularly CD4 cells or lymphocytes. Reverse transcriptase converts HIV genetic material, which is RNA, into human genetic material, which is DNA. The human-like DNA of HIV then becomes part of the infected person's own cells, allowing the cell to produce RNA copies of the HIV that can then go on to attack other not yet infected cells. Thus, blocking reverse transcriptase prevents HIV from taking over (infecting) human cells.
In general, most antiviral regimens for HIV disease contain a backbone of at least two NRTIs. The NRTIs include zidovudine (Retrovir, ZDV), stavudine (Zerit, d4T), didanosine (Videx, ddI), zalcitabine (HIVID, ddC), lamivudine (Epivir, 3TC), emtricitabine (Emtriva, FTC), abacavir (Ziagen, ABC), tenofovir disoproxil fumarate (Viread, TDF), and tenofovir alafenamide (Descovy, TAF). The latter drug is a new formulation of tenofovir that is now part of multiple fixed-dose combinations. This form of tenofovir has been shown to be equally effective as TDF but with less renal and bone toxicity. The NRTIs FTC and 3TC are highly related compounds and, although data is somewhat limited, most experts agree that they probably can be used interchangeably. That said, many combinations of NRTIs can be used together, with current guidelines generally recommending the fixed-dose combination of TDF with FTC (Truvada), or TAF with FTC (Descovy), both of which are also available as part of single tablet regimens. An alternative regimen uses the fixed-dose combination of ABC/3TC (Epzicom) alone or combined as a single tablet regimen with DTG (Triumeq). ABC has been associated with severe allergic reactions in approximately 5% of patients. Recent studies have shown that a blood test (HLA-B*5701) can be performed to determine who is at risk for this reaction so that the drug can be avoided in these individuals and be used in others with greater confidence that there will not be such a reaction. In fact, when available, it is now the standard of care to perform this test prior to initiation of ABC. The main side effects associated with TDF are reduced kidney function and bone density.
What are the usual dosing schedule and meal restrictions for NRTIs?
|ZDV, zidovudine; d4T, stavudine; ddI, didanosine; ddC, zalcitabine; 3TC, lamivudine; ABC, abacavir; TDF, tenofovir disoproxil fumarate; TAF, tenofovir alafenamide; FTC, emtricitabine.|
*Dosed at 10 mg when combined in single tablet regimen with EVG/COBI/FTC/TAF
|Dose in each pill (mg)||300||30 or 40||100 or 400||0.75||150 or 300||300||300||25*||200|
|Schedule||1 twice a day||1 twice a day|
2 (100) twice a day or
1 (400) once a day
|1 thrice a day||1 (150) twice a day or 1 (300) once a day||1 twice a day or 2 once a day||1 once a day||1 once a day||1 once a day|
30 minutes before or 60 minutes after a meal
The following are available fixed-dose combination pills of NRTIs:
- ZDV/3TC (300 mg/150 mg) as Combivir; one twice per day
- ZDV/3TC/ABC (300 mg/150 mg/300 mg) as Trizivir; one twice per day
- ABC/3TC (600 mg/300 mg) as Epzicom; one per day
- TDF/FTC (300 mg/200 mg) as Truvada; one per day
- TAF/FTC (25 mg/200 mg) as Descovy; one per day
These are standard doses for average-sized adults, and dosing may vary depending upon the weight of a patient. Certain combinations of drugs in this class should generally be avoided, including d4T with ZDV or ddI, 3TC with FTC, and TDF with ddI.
The new formulation of tenofovir (TAF) is available as combination pills only, including EVG/COBI/FTC/TAF (Genvoya, 150/150/200/10 mg), FTC/TAF (Descovy, 200/25 mg), TAF/FTC/RPV (Complera, 25/200/25 mg), BIC/FTC/TAF (25/200/25 mg), and darunavir (DRV)/Cobicistat (COBI)/FTC/TAF (800/150/200/10 mg). The new formulation of tenofovir results in lower plasma levels and higher intracellular concentrations of the active drug. Data demonstrate that compared to TDF-containing regimens this form is equally effective with less adverse effects on bone mineral density and possibly on the kidneys.
What are nonnucleoside analogue reverse transcriptase inhibitors (NNRTIs)?
Like NRTIs, NNRTIs block the reverse transcriptase enzyme, preventing uninfected cells from becoming infected.
NNRTIs include nevirapine (NVP), delavirdine (DLV), efavirenz (EFV), etravirine (ETR), rilpivirine (RPV), and doravirine (DOR). ETR was developed specifically to be an option for patients who have developed resistance to the earlier drugs in the class. NVP, DLV, EFV, RPV, and DOR are typically used with two NRTIs, and ETR is primarily being used as part of regimens for those with a history of different types of treatment to which they have developed resistance.
|NVP, nevirapine; DLV, delavirdine; EFV, efavirenz; ETR, etravirine; RPV, rilpivirine; DOR, doravirine.|
*A new formulation is available for dosing as one 400 mg tablet (Viramune XR) once a day.
each pill (mg)
|Schedule||1 twice a day|
(start with 1 once a day
for first 14 days)
|2 thrice/day||1 once a day||1 twice a day||1 once a day||1 once a day|
|Meal restrictions||None||None||Avoid high-fat meals||After meals||With meals||None|
For people without a history of drug resistance, there are now three effective fixed-dose combination pills that include TDF, plus FTC with either EFV (Sustiva) or RPV (Complera), or plus 3TC with DOR, all of which are available as a single pill that can be taken once per day. There is also a formulation of TAF plus FTC with RPV (Odefsey). The combination with RPV (Complera) was shown to be very effective and well tolerated but not as good at suppressing the viral load as the combination with EFV (Atripla), particularly amongst those who started therapy with higher viral loads and lower CD4 cell counts (for example, >100,000 copies/mL and <200 cells/mm3, respectively). It is currently recommended only for those that have viral load levels of <100,000 copies/mL and CD4 cell counts greater than 200 cells/mm3.
Latest HIV News
Daily Health News
What are protease inhibitors?
PIs block the action of an HIV enzyme called protease that allows HIV to produce infectious copies of itself within HIV-infected human cells. Thus, blocking protease prevents HIV in already-infected cells from producing HIV that can infect other, not yet infected cells.
- saquinavir (Invirase and Fortovase, SQV), which comes as the hard gel capsule Invirase (INV),
- ritonavir (Norvir, RTV),
- indinavir (Crixivan, IDV),
- nelfinavir (Viracept, NFV),
- fosamprenavir (Lexiva, FPV),
- lopinavir/ritonavir (Kaletra, LPV/r),
- atazanavir (Reyataz, ATV), and
- tipranavir (Aptivus, TPV),
- darunavir (Prezista, DRV).
Each of these drugs has been shown to effectively reduce the viral load when used in combination with other active drugs.
LPV/r comes coformulated as Kaletra while all other RTV-containing regimens require taking RTV along with the other PI. In the case of TPV, RTV must be given as 200 mg with each dose of TPV twice per day. In contrast, ATV can be given without RTV at a dose of two 200 mg capsules once daily or 300 mg with 100 mg RTV once daily. The latter should always be used in PI-experienced subjects and when used in combination with TDF or NNRTIs which can reduce the drug levels of ATV. Similarly, FPV is also used differently in PI-naïve and experienced individuals. In treatment-naïve individuals, it can be given as two 700 mg tablets twice daily or two 700 mg tablets (1,400 mg total) with either 100 or 200 mg RTV, all once daily. In treatment-experienced patients, or when used with NNRTIs, it should be given as one 700 mg tablet with 100 mg RTV, both twice daily. The most recently approved of the PIs is DRV, which was initially used exclusively in treatment-experienced patients with drug-resistant virus. In this setting, it is given as 600 mg with 100 mg RTV, both given twice daily. More recently, DRV was approved for those who have never been treated before given at a dose of 800 mg once daily with 100 mg of RTV once daily.
|SQV, saquinavir; IDV, indinavir; NFV, nelfinavir; FPV, fosamprenavir; LPV/r, lopinavir plus ritonavir; ATV, atazanavir; TPV, tipranavir; DRV, darunavir.|
1Administered with RTV at a dose of 100 mg twice a day.
2FPV can be given without RTV in patients without resistance to PIs or at a dose of 1,400 mg once daily with either 100 mg or 200 mg of RTV once daily. In treatment-experienced patients, FPV is given at a dose of 700 mg twice daily with RTV 100 mg twice daily.
3ATV can be given alone at a dose of 400 mg once daily or at a dose of 300 mg once daily with RTV 100 mg or COBI 150 mg once/daily.
4TPV is always given at a dose of 500 mg twice/daily with RTV 200 mg twice daily.
5DRV can be given to those with a history of drug resistance at a dose of 600 mg twice daily with 100 mg RTV twice daily. For those without resistance, it can be given at a dose of 800 mg with 100 mg RTV or 150 mg COBI once daily.
|Dose in each pill (mg)||500||400||625||700||200/50||200 or 300||250||400 or 600|
|Schedule||21 twice a day||2 every 8 hours||2 twice a day||2 twice a day or with RTV2||2 twice a day or 4 once a day||2 (200) or 1 (300) with RTV or COBI3 once a day||24 twice a day||8005 once a day with RTV or COBI given once per day or 600 twice a day with RTV given with each dose5|
|Meal restrictions||With large meals||1 hour before or 2 hours after meals, or with low-fat meals||With meals||None||With meals||With meals||With meals||With meals|
Although RTV is approved for treatment of HIV-infected patients at a dose of 600 mg twice daily, it is virtually never used at this dose because of severe side effects. Because of this, it is not included in the above table. However, PIs are frequently dosed with low doses of RTV. RTV delays the clearance of the other drugs from the system, making them easier to take and more effective. The dose of RTV varies depending upon which drugs it is being taken with and how it is being administered. The only PI that is not substantially affected by RTV is NFV. Another recently approved boosting agent is COBI which has no anti-HIV activity but can be given with once daily ATV or DRV as an alternative to RTV for pharmacologic boosting. There are also fixed-dose combinations of each, for example, ATV 300 mg combined with COBI 150 mg (Evotaz) and DRV 800 mg combined with COBI 150 mg (Prezcobix). A single-tablet formulation is now also available with DRV/COBI/FTC/TAF (800/150/200/10 mg) once daily.
What are fusion inhibitors?
A fusion inhibitor blocks an early step in the viral life cycle. Enfuvirtide (Fuzeon, T-20) attaches to the envelope surrounding the virus and prevents it from entering the CD4 cells. This prevents the infection of CD4 cells by HIV. T-20 is the first approved drug in this class. It is given as a twice-daily subcutaneous injection (90 mg). It is used primarily in individuals who have developed resistance to other classes of drugs in order to create a new potent combination. Like all other antivirals, it is most useful in those taking other active drugs at the same time in order to optimize the chance of getting viral loads to undetectable levels and to prevent the development of drug resistance.
Subscribe to MedicineNet's General Health Newsletter
What is a CCR5 antagonist?
The only available drug in this class is called maraviroc (Selzentry, MVC), which is now approved for use in combination therapy in treatment-experienced and naïve patients who do not have detectable CXCR4-using virus as determined by a tropism assay. This is a unique drug in a new class that blocks viral entry by interacting with the CCR5 molecule on the surface of the CD4 cell. It is known that HIV first binds to the CD4 molecule on the surface of CD4 cells and then connects with the CCR5 or CXCR4 molecule. Only after this second step is the virus able to enter the cell. The CCR5 antagonist prevents viruses that use CCR5 from getting into the cell. What is unique about this drug compared to others is that 20%-50% of patients have viruses that are able to use the CXCR4 receptor. In these cases, CCR5 antagonists do not appear to be active at suppressing virus. Therefore, in order to know if the drug will work for a given patient, a new test needs to be performed, the so-called tropism assays. This test will tell the provider and patient whether there is virus that uses CXCR4, in which case the patient would not be a candidate for MVC, or if they only have viruses that use CCR5, in which case MVC should be an active drug. Without tropism results, it is impossible to know whether MVC will be an active drug for a given patient.
MVC is typically dosed at either 300 mg or 150 mg twice daily, depending upon what other drugs it is given with. If the patient is taking any RTV, then they would usually receive the 150 mg dose. If RTV is not being used as part of the regimen, they would generally receive the 300 mg dose and sometimes even higher if it is being used with drugs like ETR. HIV providers are aware that whenever using any anti-HIV medications attention must be given to possible drug interactions.
What is an integrase strand transfer inhibitor?
The first available drug in this class was RAL, which is very potent at suppressing HIV in all patients who have never been on this drug or others in the class. It was initially approved for treatment-experienced patients with drug-resistant virus. It is also now approved for those starting therapy for the first time. The approved dose of RAL is 400 mg twice daily with a newer formulation that can be given to those starting therapy for the first time or stably suppressed on RAL twice daily that can be given as two 600 mg tablets once daily. As noted above, a second drug in this class, EVG, is approved for use as first-line therapy as part of the fixed-dose combination pill of TDF/FTC/COBI/EVG and more recently TAF/FTC/COBI/EVG as a stand-alone drug for use in treatment-experienced patients combining it with a ritonavir-boosted PI. This drug is well tolerated and given as one pill per day, but unlike RAL it does need to be taken with food and it has interactions with other drugs since it must be used with RTV or COBI, so it must be used with caution in those on multiple medications. Another InSTI, DTG is currently recommended for those starting therapy for the first time with either TDF/FTC or ABC/3TC and is available as a fixed-dose combination of ABC/3TC/DTG that can be given as a single pill per day. This drug has a limited number of drug-drug interactions and is generally well tolerated with resistance rarely emerging in those experience virologic failure. It is also frequently active in those who have developed InSTI resistance to RAL and EVG, although it often needs to be given in this setting at a dose of 50 mg twice daily. The most recently approved InSTI is called bictegravir (BIC) that has few drug-drug interactions, is potent, well-tolerated, and can be given with or without food. It is only available as a single-tablet regimen as BIC/FTC/TAF. Thus far, data suggests that selection of drug resistance in those starting therapy with this regimen is extremely rare.
|RAL, raltegravir; EVG, elvitegravir; DTG, dolutegravir; BIC, bictegravir. 1Currently, it is approved as part of the fixed-dose combination pill of EVG (150 mg)/COBI (150 mg)/FTC (200 mg) with either TDF (300 mg) or TAF (25 mg). 2DTG must be given twice per day in patients with history of InSTI resistance. BIC is only available at single-tablet regimen BIC (50 mg)/FTC (200 mg)/TAF (10 mg). 3Available at dose of 600 mg tablet given as two pills once daily for those starting therapy for first time or stably suppressed on a regimen with 400 mg given twice daily.|
|Dose in each pill (mg)||4003||150||502||50|
|Schedule||1 twice a day||1 per day||1 per day||1 per day|
|Meal restrictions||None||With food||None||None|
Two large studies recently demonstrated that in those with viral loads less than 500,000 copies/mL a regimen of DTG plus 3TC was as effective in suppressing viral after one year as the traditional regimen of DTG with two NRTIs. This regimen will likely soon be available as a single-tablet regimen for initial therapy in those without chronic hepatitis B, no underlying drug resistance, and viral loads less than 500,000 copies/mL.
There are now 10 approved combination pills that allow for a full regimen to be taken as a single pill once per day, so called single tablet regimens. This includes the following NRTI plus third drug combinations:
- TDF/FTC/EFV (300/200/600 mg) as Atripla
- TDF/FTC/RPV (300/200/25 mg) as Complera
- TAF/FTC/RPV (25/200/25 mg) as Odefsey
- TDF/FTC/EVG/COBI (300/200/150/150 mg) as Stribild
- TAF/FTC/EVG/COBI (25/200/150/150 mg) as Genvoya
- ABC/3TC/DTG (600/300/50 mg) as Triumeq
- BIC/FTC/TAF (50/200/10) as Biktarvy
- DRV/COBI/FTC/TAF (800/150/200/10) as Symtuza
- DOR/3TC/TDF (100/300/300) as Delstrigo
- DTG/RPV (50/25) as Juluca, which is only approved for those stably suppressed on an alternative regimen with no history of drug resistance
What is an entry inhibitor?
A monoclonal antibody called ibalizumab (Trogarzo) binds the CD4 molecule (a receptor for HIV on cells), which prevents viral entry into the cell. Medical professionals administer the drug as an intravenous infusion of 2,000 mg once, then two weeks later at 2,000 mg again, followed by 800 mg every two weeks. It is appropriate for heavily treatment-experienced patients with multidrug resistant virus who need new therapeutic options in order to achieve an undetectable viral load.
What HIV drugs are in development?
There are many drugs currently in development that may simplify therapy and provide important options for those who have developed extensive drug resistance. Drugs that show promise in early clinical trials are often made available by the manufacturer to certain individuals with approval of the FDA. In particular, these drugs are used in individuals who are no longer responding or able to tolerate currently available agents. The next drugs likely to be approved for use will be long-acting injectable formulation of RPV in development along with a long-acting new InSTI called cabotegravir (CAB). An early stage study showed that the combination of short-acting RPV and CAB was able to maintain virologic suppression in those with a suppressed viral load. A follow-up study showed maintenance of suppression with the long-acting regimen given intramuscularly once monthly and every other month. There are three large studies under way to definitively address safety and efficacy of this regimen given either monthly or every other month.
Health Solutions From Our Sponsors
DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents. "Guidelines for the Use of Antiretroviral Agents in HIV-1 Infected Adults and Adolescents." Washington D.C.: Department of Health and Human Services, 2018. <https://aidsinfo.nih.gov/contentfiles/lvguidelines/adultandadolescentgl.pdf>
Top HIV Medications List and Drug Charts Related Articles
HIV Early Signs and StagesHuman immunodeficiency virus or HIV, destroys important cells that fight disease and infection, which weakens a person's immune system. Some people with HIV don’t have any signs or symptoms. Early signs and symptoms of HIV infection include mononucleosis-like or flu-like symptoms, which include body aches, fever, and headache. Signs and symptoms begin around seven or eight years after HIV infection, which include weight loss, loss of energy and appetite, and swollen lymph nodes. There are 3 stages of HIV.
HIV/AIDS Facts: What Is HIV?
HIV (human immunodeficiency virus) is the precursor infection to AIDS (acquired immunodeficiency syndrome). HIV is transmitted through blood and genital secretions; most people get it through sexual contact or sharing needles for illegal IV drug use. HIV can be controlled by a strict drug regimen, but left unchecked, it leads to AIDS. In AIDS, the immune system collapses and the body falls prey to secondary, opportunistic infections and cancers that typically kill the person.
HIV/AIDS Infection Transmission and PreventionHIV (human immunodeficiency virus) is spread through contact with genital fluids or blood of an infected person. The spread of HIV can occur when these secretions come in contact with tissues such as those lining the vagina, anal area, mouth, eyes (the mucus membranes), or with a break in the skin, such as from a cut or puncture by a needle.
HIV/AIDS Testing: Diagnosis and MonitoringHIV/AIDS diagnosis and monitoring have come a long way from the days when a diagnosis was a death sentence. Crucial parts of the effective treatment regimens developed in the last 40 years are consistent monitoring of the viral load (the amount of virus in the blood), and the immune cell count, which function as biological markers of the disease’s progression. Doctors also must test for drug resistance.
HIV vs. AIDSHuman immunodeficiency virus causes HIV infection. Acquired immunodeficiency syndrome (AIDS) is a condition that results after HIV has extensively damaged a person's immune system. Risk factors for HIV and AIDS include use of contaminated needles or syringes, unprotected sex, STDs, receiving a blood transfusion prior to 1985 in the United States, having many sex partners, and transmission from a mother to her child.
Human Immunodeficiency Virus (HIV)
HIV (human immunodeficiency virus) infection left untreated causes AIDS (acquired immunodeficiency syndrome). Still incurable, AIDS describes immune system collapse that opens the way for opportunistic infections and cancers to kill the patient.
- Early symptoms and signs of HIV infection include flu-like symptoms and fungal infections, but some people may not show any symptoms for years.
- Highly active antiretroviral therapy (ART) is the standard treatment for HIV infection. These combination drug regimens have made HIV much less deadly, but a cure or vaccine for the pandemic remains out of reach.
- HIV is usually transmitted through sexual contact or sharing IV drug needles, but can also infect someone through contact with infected blood.
- Sexual abstinence, safe sex practices, quitting IV drugs (or at least using clean needles), and proper safety equipment by clinicians and first responders can drastically reduce transmission rates for HIV/AIDS.
What Are the Side Effects of HIV Medications?It’s important to know the potential side effects of all the drugs you take to control your HIV infection, as well as potential drug interactions. All of the NNRTIs (nonnucleoside analogue reverse transcriptase inhibitors), for example, are associated with important drug-drug interactions so they must be used with caution in patients on other medications. Learn more about the side effects of the drugs in standard treatment regimens.
When should you start HIV medication?Nearly everyone who is infected with HIV (human immunodeficiency virus) should start antiviral medication therapy as soon as they are diagnosed. Older guidelines recommended delaying treatment to help reduce the potential for drug side effects and viral resistance to treatment. Current thinking theorizes that early treatment may preserve more of the body's immune function.