Uses

NRTIs are used for the treatment and management of HIV. In some cases, NRTIs are also used to treat chronic hepatitis B.

NRTI Medications Currently Used in the United States

Before Taking

When healthcare providers prescribe NRTIs, they take a variety of factors into consideration, including:

The sensitivity of the strain of HIVContraindicationsAdverse reactionsA person’s current medications

It is recommended that HIV treatment—including NRTIs—start on the day a person is diagnosed with HIV, in order to give it the best chance of working and slowing the progression of the disease.

How NRTIs Are Prescribed

Currently, the standard HIV treatment involves a combination of:

NRTIsNNRTIsProtease inhibitorsIntegrase strand transfer inhibitors

The recommended guidelines include the use of Dovato (dolutegravir and lamivudine) for those newly diagnosed who do not have a viral load greater than 100,000. It is the only two-drug regimen that is recommended and only has one NRTI backbone.

For newly diagnosed HIV infections, NRTIs are used in combination with an integrase inhibitor. The two recommended treatment protocols are:

Dolutegravir + Tenofovir Alafenamide + Emtricitabine 

Dosage: This regimen consists of taking three tablets. Dolutegravir, emtricitabine, and tenofovir alafenamide tablets are available containing 52.6 mg of dolutegravir sodium (DTG), equivalent to 50 mg of dolutegravir; 200 mg of emtricitabine (FTC); and 28.04 mg of tenofovir alafenamide fumarate (TAF), equivalent to 25 mg of tenofovir alafenamide. The 50 mg/200 mg/25 mg tablets are white to off-white, film-coated, oval, unscored tablets debossed with M on one side of the tablet and TD1 on the other side. 

Instructions: Take with or without food.

Bictegravir + Tenofovir Alafenamide + Emtricitabine (Biktarvy) 

Doseage: The brand name of this tablet is Biktarvy. Each tablet contains a combination of all three medications: 50 mg of bictegravir; 200 mg of emtricitabine; and 25 mg of tenofovir alafenamide.

Instructions: Take with or without food. Do not take with any other HIV medications.

Side Effects

While NRTIs are generally safe, like any drugs, they may cause certain side effects. Common and minor side effects of NRTIs (which typically resolve on their own) include:

Headache Nausea Vomiting Diarrhea Upset stomach

Most of the following more serious side effects appear gradually after chronic use.

Mitochondrial Toxicity

Both the most common and most significant side effect associated with the use of NRTIsLess common in newer NRTIsCan manifest as one of the following: myopathy, lipoatrophy, neuropathy, and lactic acidosis with or without hepatic steatosis

Myopathy

Most commonly associated with zidovudineCan manifest as proximal muscle tenderness and myalgias

Lipoatrophy

Also known as lipodystrophyThe loss of body fat from the face and extremities (loss of fat from areas of the cheek, temples, and the periorbital regions gives patients emaciated appearance)Strongly correlates with the use of protease inhibitors in highly active antiretroviral therapy (HAART); can also appear in association with stavudine use

Peripheral Neuropathy

Most common with chronic use of zalcitabine, didanosine, and lamivudine

Lactic Acidosis

Most commonly occurs with the use of zidovudine, lamivudine, stavudine, and didanosineHepatic steatosis often occurs accompanying lactic acidosis due to decreased mitochondrial beta-oxidation of fatty acids resulting in esterified triglycerides that accumulate in the liver

Warnings and Interactions

The warnings for and interactions with NRTIs differ depending on the type of medication. These include:

Zidovudine

Do not co-administer with stavudine, as zidovudine may reduce the phosphorylation of stavudine. Avoid concurrent use of myelosuppressive drugs (e. g. , ganciclovir, ribavirin).

Didanosine

The chewable formulation contains antacid (therefore avoid taking fluoroquinolones and tetracycline within two hours before or after didanosine). Avoid alcohol (increased risk of pancreatitis) and concurrent neuropathic drugs (e. g. , didanosine, zalcitabine, isoniazid).

Lamivudine

Lamivudine’s AUC (area under curve) increases when co-administered with trimethoprim-sulfamethoxazole.

Stavudine

Do not co-administer with zidovudine, as zidovudine may reduce the phosphorylation of stavudine.

A Word From Verywell

While there is still no cure for HIV, several available treatment options can extend the life of a person living with the virus. NRTIs are one of the earliest classes of antiretroviral drugs, meaning that researchers and healthcare providers have a more complete picture of their safety and effectiveness.

NRTIs play an important role in HIV treatment and maintenance, especially given that the recommended treatment for newly diagnosed HIV infections includes two NRTIs, along with a third drug. As with any medication, ask your healthcare provider any questions you have about your prescription and/or drug combination. Be sure to mention any preexisting conditions so they can find a medication that works best for you.

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