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Some of the most effective HIV treatments don’t rely on a single medication, but on combinations that work better together. Two medicines often used this way are emtricitabine and tenofovir. Used separately or in combination, they belong to a class of medicines called antiretrovirals (ARVs). These medicines stop HIV from making more copies of itself, which lowers the amount of virus in the body.
Both emtricitabine and tenofovir are part of a smaller group of HIV medicines called NRTIs (short for nucleoside/nucleotide reverse transcriptase inhibitors). In simpler terms, they block a protein HIV needs to make copies of itself.
In this article, we’ll explain how NRTIs like emtricitabine and tenofovir work. We’ll also cover when doctors prescribe them and what side effects to watch for.
NRTIs were the first type of ARV drugs approved by the U.S. Food and Drug Administration (FDA) to treat HIV. They are still used today. For example, the current standard treatment for people living with HIV is two NRTI drugs and one drug from a different ARV class (called a 2+1 combination). NRTIs are also used to prevent HIV infection in people at high risk of contracting the virus.
HIV is managed with combinations of medications, each blocking the virus at a different stage of its life cycle. One stage is when HIV creates the DNA it needs to take over immune cells — the step blocked by NRTIs.
When someone is first infected with HIV, the virus enters immune cells in their blood. HIV needs to be inside an immune cell and make a special kind of DNA before it can take over the cell and make more copies of itself. During this process, the immune cell can die and release new copies of HIV into the bloodstream. From there, the new copies of the virus can infect other immune cells. NRTIs block HIV from making the DNA it needs, so fewer immune cells are destroyed and fewer copies of the virus are made.
Emtricitabine is a commonly prescribed NRTI. It’s available as a pill that’s usually taken once a day. Like other ARVs, emtricitabine is taken in combination with other drugs to control HIV infection. Studies have shown that emtricitabine drug combinations reduce the amount of HIV in the body and increase the number of immune cells.
Like all ARVs, emtricitabine comes with some possible side effects, including:
One specific side effect that has been reported, especially in African Americans, is skin color changes on the palms of the hands and soles of the feet, according to StatPearls, a medical reference reviewed by doctors. This has also been seen on the tongue, arms, lips, and nails, but it’s rare.
Less common side effects of emtricitabine include lactic acidosis (a buildup of lactic acid in the blood) and hepatomegaly (liver enlargement). Risk factors for these conditions include female sex, obesity, and liver disease, according to the Journal of the International Association of Providers of AIDS Care. These serious side effects are possible with other NRTIs as well.
Tenofovir is another commonly prescribed NRTI. It comes in two different forms: tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF). These two forms of the medication work differently in the body. They’re both very effective at blocking HIV from making the DNA it needs to take over immune cells. This helps stop HIV from making more copies of itself.
TDF is the older form of tenofovir approved by the FDA. After over a decade of use, studies showed that people taking TDF were at a higher risk of bone and kidney damage. The risk of these side effects was highest in people with advanced HIV, long-term TDF treatment, low body weight, and preexisting kidney conditions. This led to the development and approval of TAF, a newer form of tenofovir that reduced those serious side effects.
Because tenofovir is an NRTI, both forms of the drug still carry a small chance of lactic acidosis and liver enlargement. The same risk factors apply when taking tenofovir.
In addition to possible bone and kidney damage after long-term use, other common side effects of TDF include:
Your healthcare provider will check your kidneys before prescribing TDF. Your kidneys will also be monitored by blood and urine testing while you’re taking it. Using TDF with high-dose nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen is not recommended because it can raise the risk of kidney damage.
Because of the effects of TDF on bone density, you may also be prescribed a calcium and vitamin D supplement while taking this drug. This is to help prevent the loss of bone density that TDF can cause.
The most common side effects with TAF include:
The risk of kidney and bone damage is lower with TAF. That means this drug may be safer for people with kidney problems or a history of osteoporosis (low bone density) or bone fractures.
One specific complication of TAF is higher cholesterol. Scientists are not sure whether this has any long-term health effects, though.
Emtricitabine and tenofovir are often used together for HIV treatment and for preventing HIV in people at high risk. Truvada combines tenofovir disoproxil fumarate (TDF) and emtricitabine. Descovy combines tenofovir alafenamide (TAF) and emtricitabine. Some combination pills also add other drugs. For example, Stribild (elvitegravir, cobicistat, emtricitabine, and TDF) and Genvoya (elvitegravir, cobicistat, emtricitabine, and TAF) each contain four drugs in a single pill.
For someone living with HIV, at least three medications are usually prescribed together to manage the virus. As someone’s HIV infection and health change over time, the specific medications used might change. But for someone diagnosed with HIV for the first time, the recommended drug combinations are:
The goal of preexposure prophylaxis (PrEP) is to reduce the risk of HIV infection in people at high risk. PrEP is 99 percent effective at reducing HIV infection from sexual activity. It’s also 74 percent effective in reducing HIV infections from injectable drug use. The medicine is only effective if it’s taken every day as prescribed.
The U.S. Centers for Disease Control and Prevention (CDC) recommends a once-daily dose of emtricitabine and TDF (Truvada) or emtricitabine and TAF (Descovy) for PrEP. According to the CDC, people at high risk for HIV infection who might be prescribed this medication include:
In addition to these pills, the CDC also recommends a form of PrEP called cabotegravir (Apretude), which is injected every two months. Another injectable PrEP medication called lenacapavir (Yeztugo) is given once every six months and has been approved by the FDA.
Another use of the emtricitabine-tenofovir combination drug is in postexposure prophylaxis (PEP). This means the medicine is used to help prevent HIV infection in people who think they may have been exposed to HIV. This could happen if you come into contact with blood, genital fluids, or other body fluids from someone who has HIV or whose HIV status is unknown.
The CDC now recommends a different medicine combination for PEP. Most people should take either one pill that has bictegravir, emtricitabine, and tenofovir alafenamide, or a combination of dolutegravir plus tenofovir (either alafenamide or disoproxil fumarate) and either emtricitabine or lamivudine. Your doctor will help choose the best option for you.
How long someone takes these specific medications depends on what they’re being used for. For someone with a confirmed HIV diagnosis, treatment continues throughout their life. In this situation, it’s especially important to take your HIV treatment every day or as directed by your healthcare provider. Missing doses gives the virus time to mutate (change) and might make the medication stop working.
If someone is taking these medications as part of PrEP or PEP, the timing will vary. In general, a 28-day course of medication is recommended for PEP. How long you need PrEP treatment depends on your situation. Your best resource is your healthcare team — they can answer any questions you might have about which HIV drugs you’re taking and why.
On myHIVteam, the social network for people with HIV and their loved ones, members come together to ask questions, give advice, and share their stories with others who understand life with HIV.
Have you tried emtricitabine-tenofovir combination treatment? Share your tips and experiences in a comment below or on your Activities page.
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My infectious disease doctor changed my daily regime to Biktarvy, a three-pronged AVT and NVT for HIV treatment about 4 years ago now. Adjusting well. Truvada and Tivicay were my previous treatments… read more
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