Truvada (Tenofovir Disoproxil Fumarate): Side Effects and Safety Concerns

Truvada treats and prevents HIV (Human Immunodeficiency Virus), but the active ingredient, TDF (tenofovir disoproxil fumarate), has been linked to major potential side effects like liver, kidney and bone damage.

When first introduced in 2004, Truvada represented a major advancement in treating and preventing HIV. Over time, serious safety concerns and side effects have surfaced, leading to FDA black box warnings and multiple lawsuits.

Truvada works by interfering with HIV viral reproduction, making it more difficult for the virus to replicate and spread in the body. The mechanism TDF uses to slow HIV or prevent infection, however, can lead to severe side effects. In recent years, alternatives to TDF have proved effective at treating and preventing HIV with significantly less risk of damage to bones or organs.

Truvada (TDF) remains an important option for HIV treatment and prevention, but its risks, including serious side effects and FDA black box warnings, cannot be ignored. Newer alternatives may provide safer ways to achieve similar results with fewer health concerns.

TDF is an antiretroviral medication used to treat and prevent HIV and AIDS (Acquired Immune Deficiency Syndrome).

TDF was first sold under the brand name Viread, and is the active ingredient in several other branded drugs, including Atripla, Complera and Truvada (emtricitabine and tenofovir disoproxil fumarate).

Gilead Sciences introduced TDF to the market in 2001, and Truvada — the first drug to combine TDF with another antiretroviral — was introduced in 2004. Since 2020, generic forms of Truvada (a combination of Emtricitabine and TDF) have been available. Hence, the name “Truvada” only refers to the specific formulation from Gilead and not similar drugs or identical generics.

According to the National Center for Biotechnology Information, TDF works by interfering with reverse transcriptase, an enzyme that HIV needs to replicate itself and spread through the body. After TDF is processed, it becomes a sort of “decoy” that HIV incorporates into its DNA. With these decoys in place, the DNA can no longer replicate, which prevents HIV from spreading to other cells or continuing to multiply.

TDF was originally used for the treatment of HIV in combination with other antiretrovirals. Later, TDF was approved for use in pre-exposure prophylaxis (PrEP) – as a daily preventative medicine to prevent HIV in high-risk individuals.

Every drug has side effects, and TDF is no different. Many of the common TDF side effects are shared with lots of other drugs. Common TDF side effects include:

These common side effects may seem familiar and relatively mild, as they are similar to those associated with ibuprofen.

TDF has some more concerning possible side effects, however:

These serious side effects from Truvada usually appear with long-term use. Since TDF for PrEP is often taken daily for many years, sometimes decades, the risk of experiencing these effects increases over time.

Black box warnings are the most serious warnings the FDA issues. These warnings are intended to alert people to significant risks and require doctors to review these risks before prescribing.
The FDA’s Truvada black box warnings address worsening of existing hepatitis B, lactic acidosis, severe hepatomegaly with steatosis and resistance to Truvada developing in patients using it for PrEP.

Patients with Hepatitis B can experience worsening symptoms or even a reactivation of the hepatitis B virus, HBV, in their bodies. Additionally, patients who stop taking Truvada may also experience worsening hepatitis B symptoms.

Lactic acidosis is a buildup of lactic acid in the blood. While rare, this condition can be fatal if left untreated.

Hepatomegaly with steatosis, also known as fatty liver, occurs when excess fat cells accumulate in the liver cells, causing the liver to enlarge. This condition can lead to fatigue, jaundice and confusion.

If a patient begins using Truvada for PrEP but has already contracted HIV, their HIV can become resistant to Truvada, making treatment more difficult.

In addition to the black box warnings, Truvada is associated with several other potentially serious side effects. Many of these are directly connected to TDF, which is present in Truvada and several other medications used to treat or prevent HIV.

Newer drugs like Descovy use an alternative to TDF called tenofovir alafenamide, or TAF. TAF works similarly to TDF in blocking HIV replication but does so more selectively, reducing stress on the kidneys and bones. It is often recommended for patients at higher risk of bone or kidney issues.\

Gilead Sciences, the maker of Truvada and Descovy, has been accused of withholding TAF from the market to maximize profits from Truvada and other TDF drugs.

Truvada and other drugs containing TDF have not been recalled in the United States.

Since its introduction in 2004, Truvada has been closely monitored, and certain long-term side effects have emerged. Some of these, which have prompted black box warnings, include:

Despite these concerns, Truvada has not faced a full FDA recall, and no specific batches have been widely recalled due to safety issues.

These side effects have also led to Truvada lawsuits seeking damages from Gilead Sciences.

Since the introduction of newer formulations like TAF, the use of TDF-containing drugs has declined, but the FDA has not issued a recall.

TDF is an effective treatment and preventative for HIV because it delivers tenofovir to cells and thereby prevents HIV from replicating. The dangers associated with TDF come primarily from the high amounts of tenofovir TDF introduces to the body. TDF introduces tenofovir to the bloodstream, where large amounts of tenofovir are circulated throughout the body and absorbed by cells. Tenofovir alafenamide, TAF, delivers tenofovir directly to cells, resulting in much lower levels of tenofovir in the bloodstream.

If you or a loved one has undergone cancer treatment, you may know the difference between chemotherapy, which affects the whole body, and targeted radiation. Similarly, TDF acts like chemotherapy, affecting the body more broadly, while TAF works more like targeted treatment.

Most side effects of Truvada and other TDF-containing drugs are linked to the amount of tenofovir in the body. Reducing tenofovir levels by up to 90 percent can significantly lower or eliminate many of these serious side effects.

According to the NIH, studies show that patients treated with TAF experience significantly fewer serious side effects compared to TDF, including lower risks to kidneys and bones.

TAF has a much smaller impact on kidney function, with a lower risk of new or worsening kidney impairment. It also causes significantly less bone mineral density loss, particularly in the hip and spine, compared to TDF.

Although TDF remains an effective option for HIV treatment and PrEP, many patients are transitioning to TAF-based alternatives. Those with pre-existing kidney problems or concerns about bone health are prime candidates for moving from TDF to TAF treatments. Older patients may also benefit from TAF treatment because of the higher risk of kidney problems and bone loss that comes with aging. Long-term users of TDF-based treatments may also benefit from a shift to TAF, since the side effects of TDF treatment tend to get worse over extended use.

Truvada and other TDF-containing drugs remain widely used, and the availability of a generic Truvada means TDF-based treatments will likely continue in cases where cost is a key factor.

If you are taking Truvada or another TDF-containing medication, it is important to understand potential side effects and take steps to protect your health. Never stop taking your medication without consulting your doctor, as this is especially important for Truvada. For patients with hepatitis B, stopping Truvada can cause reactivation or severe worsening of symptoms, which can be life-threatening.

Patients on Truvada should regularly monitor kidney and liver function, as well as bone density. Staying in close consultation with your doctor helps manage side effects and ensures you can act promptly if any issues arise.

What Are the Cons of Truvada?

While Truvada offers many benefits, TDF-containing treatments also carry risks. Patients taking Truvada long-term, such as for PrEP, may face kidney, liver and bone problems. These risks are greater for those with pre-existing conditions or a higher susceptibility to these health issues.

Truvada can also exacerbate hepatitis B symptoms and can lead to HIV becoming resistant to TDF if taken for PrEP by someone already infected with HIV.

How Long Do Truvada Side Effects Last?

Minor side effects of Truvada, such as headaches, nausea or cramps, usually subside after a few days as your body adjusts. More serious side effects, however, can persist longer or cause lasting damage, including bone loss or liver problems.

Does Truvada Cause Weight Gain?

Although some PrEP users report weight gain on Truvada, studies do not support a direct link. Research indicates that Truvada is more likely to cause weight loss than weight gain in patients taking it for PrEP.