Antiretrovirals used to treat HIV include nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors.
Nucleoside reverse transcriptase inhibitors (NRTIs)
Nucleoside reverse transcriptase inhibitors, also called nucleoside analogs or nucleosides, interfere with the life cycle of HIV by preventing the transcription of viral RNA into DNA.
Most 3- and 4-drug regimens involve 2 nucleoside analogs, chosen on the basis of convenience, potential side effects, and patient preference. Certain drugs should not be used together because of the way they interact. For example, idovudine and stavudine should not be used together, and zalcitabine should not be combined with didanosine, stavudine, or lamivudine.
Drug studies are a very active area of HIV/AIDS research, and information is updated continually. It is important for patients to find a health care provider who specializes in HIV/AIDS medicine and knows about current clinical studies. Patients who are on antiretroviral therapy must be followed closely for treatment of related side effects.
Nucleosides can cause lactic acidosis (severely elevated blood lactate level) and liver enlargement (hepatomegaly; a rare but very serious side effect that can result in death). Lactic acidosis occurs more often in women and causes fatigue, belly pain, and shortness of breath. Nucleosides should be used with caution in patients who are at risk for liver disease, and treatment should be stopped if there is any indication of lactic acidosis or liver damage. Obesity increases the risk for side effects.
In most cases, nucleosides are combined with one other nucleoside plus either a non-nucleoside or protease inhibitor. NRTIs include the following:
- Zidovudine, azidothymidine (AZT, ZDV; Retrovir)
This medication was the first FDA-approved antiretroviral drug and was the first ray of hope in the AIDS epidemic. A pivotal 1987 study showed how 6 months of AZT treatment could dramatically decrease AIDS deaths.
Initially, AZT was used alone. Today, like all nucleosides, AZT is used with 2 or more other antiretroviral medications. It is usually combined with lamivudine, didanosine, or zalcitabine. AZT should not be combined with stavudine.
The usual dose of AZT is one 300 mg pill twice a day, taken with or without food. AZT is also combined with lamivudine in a single pill called Combivir®, which is also taken twice a day. A second combination pill, Trizivir contains abacavir, lamivudine, and zidovudine.
Side effects, which may include fatigue, nausea, and headache, usually improve or disappear a few days to a few weeks after starting therapy. AZT is sometimes associated with a decrease in the number of red blood cells (anemia) and prolonged use can lead to myopathy.
- Didanosine (also known as ddI; Videx, Videx EC)
Didanosine, which was approved by the FDA for the treatment of AIDS in 1991, usually is combined with AZT, stavudine, or lamivudine. It is sometimes combined with the anticancer drug hydroxyuria, which increases its effectiveness and side effects. This combination should be used with extreme caution.
The usual dose of didanosine is two 200 mg pills per day or one 400 mg daily, taken on an empty stomach. The pills have to be chewed or crushed and dissolved in water. A newer form of swallowable didanosine (Videx EC) is also available.
Side effects or didanosine include upset stomach and diarrhea. It can also cause painful neuropathy and pancreatitis (inflammation of the pancreas). Pancreatitis is a serious, potentially life-threatening complication that is more likely to develop in patients who have advanced HIV infection. If there are any signs of pancreatitis, this drug should not be used.
- Zalcitabine, dideoxycytidine (Hivid)
This medication (also known as ddC) is the third nucleoside drug approved for the treatment of AIDS and usually is combined with AZT. The usual dose is 0.375–0.75 mg three times a day, taken with or without food.
Main side effects of zalcitabine are severe peripheral neuropathy; oral and, to a lesser extent, esophageal ulcers; and, rarely, pancreatitis. Neuropathy, which can be irreversible, occurs as a side effect in as many as one-third of all patients with advanced HIV/AIDS. If numbness, burning, tingling, or pain progresses beyond moderate discomfort, the drug should be discontinued. Zalcitabine should be used with extreme caution in patients with a history of neuropathy.
If there are signs or indications of pancreatitis, the drug should be stopped. In rare cases, liver failure and death have occurred, possibly due to underlying hepatitis B.
Three-time daily dosing and the high incidence of neuropathy have made zalcitabine a second- or third-choice medicine in the treatment of HIV.
- Stavudine (Zerit)
Stavudine (also known as d4T) is the fourth nucleoside drug approved for the treatment of AIDS and is usually combined with didanosine and lamivudine. It should not be used with AZT because those two drugs work against each other.
The usual dose is one 30 or 40 mg pill twice daily, taken with or without food. The main side effect is neuropathy and it should be used with caution when combined with didanosine or zalcitabine, because those drugs also cause neuropathy. Neuropathy is more likely to develop in people with advanced HIV/AIDS. If a patient feels any symptom of neuropathy, they should tell their physician. Rarely, stavudine causes headaches or stomach upset.
- Lamivudine (Epivir)
This drug (formerly 3TC), which was approved in 1995 to treat AIDS, is usually combined with AZT, abacavir, stavudine, or didanosine. The usual dose is one 150 mg pill twice daily, taken with or without food. Some studies show that the entire 300 mg dose can be taken once a day. Lamivudine is combined with AZT in a single pill called Combivir, which is taken twice a day. A second combination pill, Trizivir is also available. It contains AZT, lamivudine, and abacavir.
Lamivudine has very few side effects. Pancreatitis is a potentially fatal risk in pediatric patients. If a child has a history of pancreatitis or other significant risk factors for pancreatitis, the drug should be used with caution. If signs or symptoms of pancreatitis develop, lamivudine should not be used.
- Abacavir (Ziagen)
Abacavir was the sixth nucleoside drug approved to treat HIV infection and was approved in 1998. Studies have shown that it is 5 to 10 times more potent than the other nucleosides. It is especially effective when used with AZT and lamivudine plus a protease inhibitor or non-nucleoside.
The usual dose of Abacavir is one 300 mg pill twice daily, taken with or without food. A second combination pill, Trizivir, is also available. It contains contain AZT, lamivudine, and abacavir.
In clinical studies, about 5 percent of people who take abacavir develop a hypersensitivity reaction that may be fatal. This reaction causes fever, nausea, vomiting, diarrhea, upset stomach, skin rash, body aches, and fatigue; usually develops within the first 6 weeks of treatment; and gets worse with every dose. If a patient develops hypersensitivity, he or she must contact to his or her physician immediately, stop taking the drug, and never take it again.
Because of the serious, possibly fatal consequences of a hypersensitivity reaction, it is important for patients who are taking abacavir to be closely monitored by a health care practitioner.
- Tenofovir disoproxil fumarate (Viread)
This nucleoside, which is also called TDF, was approved in 2001 to treat HIV/AIDS. A combination pill, Truvada is also available. It contains tenofovir and emtricitabine.
This drug is approved to treat HIV-1 infection in adults. It is taken as a tablet once a day, with or without food, and is used in combination with other antiretrovirals. Common side effects include nausea, vomiting, and diarrhea. Viread may cause serious liver or kidney problems and lactic acidosis (severely elevated blood lactate level), and may worsen hepatitis B infections.In January 2012, an NIH study indicated that vitamin D supplements may help prevent hormonal changes and reduce the risk of bone loss in young adults being treated with tenofovir. A 2-year follow-up study is planned.
- Emtricitabine (FTC, Emtriva)
This drug received FDA approval in July 2003. It is also available in a combination pill, Truvada, which contains tenofovir and emtricitabine. Emtriva should not be used with some other antiretrovirals (e.g., Atripla, Combivir, Epivir, Epzicom). It is available in tablets and an oral solution, and is used to treat children and adults. Side effects include headache, nausea, vomiting, and skin rash. This drug can also cause lactic acidosis and severe liver and kidney problems.
- Abacavir and lamivudine (Epzicom)
This NRTI was approved in 2004 to treat HIV/AIDS in adults. It is used in combination with other antiretroviral drugs and can be taken with or without food and liquids.
Patients who have experienced a hypersensitivity reaction to abacavir should not take Epzicom. This drug may cause lactic acidosis and severe liver and kidney problems.
In August 2011, Complera was approved to treat HIV-1 infection in adults who are just starting antiretroviral therapy. Complera is a fixed-dose-combination mediation that contains emtricitabine, rilpivirine and tenofovir DF. The recommended dosage is one tablet, once a day, taken orally with food.
The FDA approved a fixed-dose combination drug that contains elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide (Genvoya) in November 2015 to treat HIV-1 infection in adults and children over the age of 12 (weighing at least 77 lbs) who have never been on antiretroviral therapy.
This medication, which can be used in patients with moderate kidney problems but is not recommended for those with severe renal impairment, can reduce viral loads. It was developed to reduce side effects and contains a newer form of tenofovir not previously approved that results in lower levels of the drug in the bloodstream and higher levels in cells where the virus replicates. In clinical studies, Genvoya was associated with less kidney toxicity and decrease in bone density. Patients should be closely monitored for liver problems, lactic acid build-up, kidney damage, and other side effects during treatment.