Tenofovir disoproxil-based pill regains its position as first choice for PrEP in the US

Two blue pills being tipped from a pill bottle into a hand.
Image by Doctor 4U. Creative Commons licence.

More than half the people taking HIV PrEP (regular medication to prevent HIV infection) in the US are now taking a generic pill containing tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC), a poster at the 30th Conference on Retroviruses and Opportunistic Infections (CROI 2023) revealed last week.

In the last year, an apparent trend to replace TDF/FTC with the tenofovir alafenamide (TAF) / emtricitabine pill branded as Descovy has reversed, with over 50% of PrEP prescriptions in the last month surveyed – September 2022 – being for generic TDF/FTC.


TDF and TAF are both prodrugs of the antiretroviral drug tenofovir. A prodrug is a drug that is taken as one formulation but is converted to the active drug in the body. When PrEP was originally licensed the only combination pill approved for it was TDF/FTC, then sold by its manufacturers Gilead Sciences as Truvada

TDF however was associated, at least with long-term use for HIV treatment, with worsening kidney function and loss of bone mineral density.

These side effects are due to the fact that tenofovir circulating in the bloodstream is eliminated via the kidneys. TAF was developed because it converts to the active form of tenofovir more quickly and is absorbed by cells faster, so less remains to circulate in the blood and damage the kidneys. It was widely promoted as a safer alternative, including for PrEP, and its combination with emtricitabine is sold as Descovy.

The switch from Truvada to Descovy was controversial, however. This was in part because while TAF clearly led to less kidney toxicity, it seemed to have side effects of its own such as weight gain and increases in cardiovascular risk factors. Switching was also interpreted as a means for Gilead to continue enjoying the revenue from tenofovir when TDF went off patent in mid-2020.

Despite this controversy, the perceived benefits of TAF have persuaded many prescribers in the US. In Europe, in contrast, Descovy has never been licensed as PrEP by the European Medicines Agency (it is licensed for treatment) and Gilead announced in October 2021 that it was not going to pursue getting Descovy licensed for PrEP there. Descovy was licensed as PrEP by the UK's drug regulator the MHRA last April, but with little fanfare and awareness remains limited.

The study

The latest figures, however, show that Descovy only enjoyed a year as the most-prescribed PrEP pill and that since late 2021 TDF/FTC – now as a generic, unpatented pill – is the most common form of PrEP in the US.

The study of PrEP prescribing patterns, by Dr Weiming Zhu and colleagues from the US Centers for Disease Control and Prevention (CDC), also shows that as of September 2022, the last month they examined, injectable PrEP had yet to gain much of a foothold in the US PrEP market, representing only 0.5% of prescriptions in that month.

Zhu and colleagues analysed the longitudinal prescribing database of IQVIA, an agency that provides healthcare data to researchers. The database aims to track what therapy a patient starts on and how it changes over time. As TDF and TAF can both be used as treatment or PrEP it’s not always obvious how patients are using them, but CDC has devised its own algorithm to spot which prescriptions are for PrEP.

The time period considered was from January 2013 to September 2022. During this time, there were 381,784 prescriptions of oral PrEP, of which 7% were for women. 

As a snapshot of current prescribing, September 2022 was considered in isolation. In this single month, there were 93,808 prescriptions of generic TDF/FTC as PrEP, 50.3% of the total. To this can be added 7065 prescriptions of brand-name Truvada, still used by a few people (4.5%), so Descovy now represents 45% of PrEP prescriptions. So far there have only been a total of 2695 prescriptions of injectable cabotegravir as PrEP (brand name Apretude), though a somewhat higher proportion of these (12.5%) have been for women.

The peak age range for oral PrEP use was 25 to 34 years, with 39% of both men and women in this range. There was a slightly higher proportion of women than men aged 13-24 (13.7% versus 12.3%, though this only represents 369 women) and a lower proportion aged over 55 (5.5% versus 8.2%).



In relation to medicines, a drug manufactured and sold without a brand name, in situations where the original manufacturer’s patent has expired or is not enforced. Generic drugs contain the same active ingredients as branded drugs, and have comparable strength, safety, efficacy and quality.


Refers to the mouth, for example a medicine taken by mouth.


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Relating to the heart and blood vessels.


The physical form in which a drug is manufactured or administered. Examples of formulations include tablets, capsules, powders, and oral and injectable solutions. A drug may be available in multiple formulations.

In terms of patterns of usage, brand-name Truvada prescriptions started to fall in the third quarter of 2019, as Descovy became available; from the third quarter of 2020, Descovy overtook Truvada as the most frequently prescribed version of PrEP. During 2020, PrEP prescriptions fell due to the COVID-19 pandemic, though they returned to pre-pandemic levels by January 2021 and have climbed since then.

Truvada’s patent stopped being enforced by September 2020, a year earlier than originally forecast, and generic TDF/FTC quickly overtook it in the market, outstripping Truvada prescriptions within two months of introduction. Descovy prescriptions continued to climb, but its pre-eminence did not last; prescriptions for generic TDF/FTC overtook it in September 2021.

This research cannot say why a majority of US prescribers switched back to TDF – or why a majority of PrEP users were happy to switch back. In 2020, a group of influential physicians said that TDF-based PrEP should be preferred to Descovy, while Dr Rochelle Walensky, now Director of the CDC, showed that generic TDF/FTC would be far more cost-effective than Descovy and enable more people to be prescribed PrEP. The fact that the clinical trial of Descovy PrEP did not include women, so it cannot be recommended to them, may also have been a factor. 

But most likely it’s simple cost pressure: budget holders faced with demands for PrEP may be deciding that paying a fraction of the cost for PrEP drugs that have relatively little disadvantage in terms of safety may, in the end, provide more benefits in terms of preventing HIV. It also brings the US back into line with the rest of the world, which almost universally prescribes TDF/FTC.


Zhu WM et al. Oral and injectable PrEP use in the United States, 2013 to 2022. Conference on Retroviruses and Opportunistic Infections, Seattle, abstract 980, 2023.

View the abstract on the conference website.

Full image credit: PrEP Emtricitabine/Tenofovir (Generic Truvada) PrEP Treatment Image 11. Image by Doctor 4U. www.doctor-4-u.co.uk Available at www.flickr.com/photos/144891950@N08/48663491198 under a Creative Commons licence CC BY 2.0.