Truvada or Descovy: which should I take for PrEP?

If you’re considering taking oral PrEP for HIV prevention, you may already know that two versions exist. One is a mixture of tenofovir disoproxil fumarate and emtricitabine (TDF/emtricitabine, sometimes also known as Truvada), and the other is a mixture of tenofovir alafenamide and emtricitabine (TAF/emtricitabine, also known as Descovy).

But how do you decide which is right for you? To help you ask questions and discuss with your doctor, here we compare TDF/emtricitabine and TAF/emtricitabine for HIV prevention.

While the same medications may be used as part of HIV treatment regimens, this page compares only how the drugs are used to protect against acquiring HIV. We have other pages  about TDF/emtricitabine and TAF/emtricitabine as part of HIV treatment.

Where are TDF/emtricitabine and TAF/emtricitabine available?

The brand-name and generic versions of TDF/emtricitabine are available as PrEP in many countries worldwide.

However, TAF/emtricitabine is only licensed for use as PrEP in the United States, Canada, United Kingdom, Australia and Taiwan. It will not be licensed in the rest of Europe in the foreseeable future. Generic versions are not generally available in high-income countries, although it is possible to import a generic product for personal use in the UK and some other countries.

In what groups of people have they been tested?

Multiple clinical trials have tested the efficacy of TDF/emtricitabine in gay and bisexual men, heterosexual men and women, transgender women, and people who inject drugs. On the other hand, only a single clinical trial tested the effectiveness of TAF/emtricitabine on gay and bisexual men, with just a few transgender women. A study with cisgender women has now begun. In addition, TAF/emtricitabine has not been tested in people who inject drugs.

As a result, cisgender women and people at risk of acquiring HIV because of needle use should take TDF/emtricitabine until more data are available, which may not be until 2024. However, cisgender women may soon have another option – vaginal rings.

Do they work differently?

HIV is a retrovirus that injects single strands of RNA into CD4 white blood cells. The virus needs a particular enzyme to convert the information stored in the RNA into DNA, which can then integrate itself into blood cells, make copies of itself, and spread.

Emtricitabine (present in both forms of oral PrEP), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF) all work by inhibiting the enzyme HIV relies on to replicate. TDF and TAF are both ‘prodrugs’, which are inactive until the human body processes them and converts them to their active form. The active forms of TDF and TAF are identical.

Taking PrEP tablets (usually daily) maintains levels of the active drugs both inside blood cells and outside (e.g. in the blood plasma and in mucous linings such as in the rectum and vagina). The levels of TDF and TAF present inside and outside of cells vary because of differences in how the body processes each. TAF is absorbed by cells faster and results in higher drug levels inside of cells and lower levels in the blood and mucous membranes than with TDF.

Maintaining drug levels inside and outside of cells both contribute to HIV protection, but it is unknown whether one is more important than the other.

Does either better protect against HIV?

Keep in mind that the effectiveness of both drugs depends on people taking them according to their doctor’s instructions. If adequate concentrations of the active drug forms are not present to inhibit the enzyme HIV relies on to replicate itself, then a person may still acquire HIV if exposed to the virus.

TDF/emtricitabine has been shown in multiple studies to have ~99% effectiveness in protecting against HIV. The one study comparing the two showed that TAF/emtricitabine was equally as effective (~99%).

Does either better withstand missed doses?

During the study comparing TDF/emtricitabine and TAF/emtricitabine, only one of the approximately 5200 participants acquired HIV despite having adequate drug levels. Seventeen others acquired HIV during the course of the study, but those people did not have adequate drug levels – probably because they missed doses.

Of those who acquired HIV, about twice as many were taking TDF/emtricitabine. Some hypothesised that this result indicates that TAF/emtricitabine might remain more effective when people miss doses.

Later studies confirmed that because TAF metabolises faster, taking TAF-based PrEP results in higher drug levels inside cells as compared to TDF-based PrEP. This also suggests TAF-based PrEP might better withstand missed doses but far from confirms it. With TDF-based PrEP, drug levels in blood plasma and on mucous membranes in the rectum can be higher than with TAF-based PrEP – and this may be as important to efficacy as drug levels inside cells.

In other words, no convincing data demonstrate that one drug remains more effective than the other when people miss doses.

What if I have hepatitis B?

Because both forms of PrEP contain tenofovir, the risks associated with stopping treatment for those with hepatitis B are the same. People with hepatitis B should consult their doctor before stopping either form of PrEP.

How do their side effects compare?

The following side effects were noted in the DISCOVER trial comparing the two forms of PrEP:

• Out of 5387 study participants, three people taking TAF/emtricitabine experienced a serious adverse event and five people taking TDF/emtricitabine did.
• After 96 weeks, 4% taking TAF/emtricitabine and 16% taking TDF/emtricitabine had a 5% or greater drop in spine bone mass density.
• Two people out of 2694 people taking TAF/emtricitabine stopped treatment because of kidney function while six people out of 2693 taking TDF/emtricitabine stopped.
• Cholesterol levels reduced in both groups, and slightly more so with TDF/emtricitabine.
• Those taking TAF/emtricitabine gained a median of 1.7kg of body weight while those taking TDF/emtricitabine gained a median of 0.5kg.

To summarise, those taking TDF/emtricitabine had less favourable outcomes in relation to kidney function and bone mineral density, while those on TAF/emtricitabine put on more weight and had poorer cholesterol outcomes.

However, medical experts concluded that the observed changes were generally so small as to not result in actual illnesses. A systematic review of TDF/emtricitabine used as PrEP by thousands of trial participants found no differences in kidney or bone harms compared with a placebo (i.e. no treatment). Furthermore, over 200,000 people have taken TDF/emtricitabine in the United States without any serious toxicities being reported.

Does one cost more than the other?

Cost may be an important factor in which version of oral PrEP you decide to take, especially if your healthcare system or insurance does not reimburse for the medication.

The patent for branded TDF/emtricitabine (Truvada) has expired, allowing multiple manufacturers to offer inexpensive generic versions that contain the same ingredients. Branded TAF/emtricitabine (Descovy) will be patent protected until 2032 and, as a result, is far more expensive than TDF-based tablets.

In other words, choosing a generic version of TDF/emtricitabine will minimise costs. If you have difficulty finding PrEP where you live, online pharmacies may be a viable option.

So which should I choose?

Despite a trend in the United States of gay and bisexual men switching from Truvada to Descovy, some experts argue this is unnecessary. Both PrEP products have an excellent safety profile, and the small differences in their potential side effects will not make a difference to most users, they say.

In the UK, draft guidelines recommend TDF/emtricitabine as the first-line choice for PrEP. Only if there is a specific concern (for example, existing kidney or bone disease) should TAF/emtricitabine be prescribed.

In the end, the decision between PrEP tablets comes down to what you and your doctor decide is best for you.