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The “Right” Option, Rather Than the “Perfect” Option: A PrEP Case Study

Clinical Thought
Clinical Thought

Released: August 13, 2026

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The choice of PrEP regimen for a specific scenario should be informed by available data based on exposure type, current comorbidities, potential for drug–drug interactions, and patient preference. But what should you do when no single PrEP regimen suits all these needs? Use this case study to learn how to examine the available options and choose the best one for your patient. Sometimes, the right PrEP option is the one that you can be sure the patient will take!

PrEP Options Case Study


Case Study:
You are caring for a 47-year-old cisgender Latino man who has sex with men who would like to start pre-exposure prophylaxis (PrEP). He states that he engages in receptive and insertive anal sex with and without condoms. His past medical history is notable for hypertension, type 2 diabetes, and stage 3b chronic kidney disease. He is hepatitis B immune, hepatitis C antibody negative, HIV antigen/antibody negative, and has an eGFR of 38 mL/min. His current medications include amlodipine, losartan, and semaglutide. He states he has sex infrequently and doesn’t want to have to take another pill every day. Unfortunately, he does not like injections and does not want to receive an injectable option.

The Ongoing PrEP Gap
Biomedical interventions for HIV PrEP have revolutionized HIV prevention, with a near-perfect efficacy of 99% for protection against HIV acquisition via sexual contact. Although PrEP use has expanded significantly since it was first FDA approved in 2012, its uptake continues to be very uneven among racial, ethnic, and gender groups, with low utilization among many populations highly impacted by HIV, including Black, Latino, female, and transgender individuals.

This case study demonstrates a clear opportunity to address these disparities on an individual level. Before reviewing the pros and cons of different PrEP options for this individual, it is important to emphasize that clinic environments characterized by sex-positive framing, LGBTQ-affirming practices, destigmatized sexual health discussions, and culturally responsive staffing are associated with improved PrEP awareness, initiation, and retention.

PrEP Options
For this person with primarily sex-related exposures, there are a number of guideline-approved options. The oldest among them, daily emtricitabine/tenofovir disoproxil fumarate (FTC/TDF), has been studied and approved for all exposure types through various clinical trials: insertive and receptive anal sex, insertive and receptive vaginal sex, and injection drug use.

FTC/TDF is also used for on-demand PrEP, also known as “2-1-1” or “event-driven” PrEP, which is dependent on the intent to engage in sexual activity, rather than a daily pill. This method has only been studied in cisgender men who have sex with men and transgender women who engage in insertive and receptive anal sex.

However, FTC/TDF is not recommended for people with an eGFR less than 60 mL/min or those with osteoporosis/osteopenia because it can cause both renal and bone toxicity. A newer version of tenofovir, tenofovir alafenamide (TAF), is not associated with those negative effects and can be used with FTC for PrEP. Daily FTC/TAF has been approved for HIV prevention in cisgender men and transgender women engaging in insertive anal and receptive anal intercourse with other men, but is not recommended for people with an eGFR less than 30 mL/min.

Long-acting (LA) injectable cabotegravir (CAB) or lenacapavir (LEN) have been approved for all exposure types except injection drug use (though the ongoing PURPOSE-4 study is evaluating LEN for this very use), and can be safely used in people with renal disease.

The “Right” Option, Rather Than the “Perfect” Option
Bringing it back to the case, based on this individual’s exposure history alone, the CDC and IAS HIV PrEP guidelines would support use of daily FTC/TDF or FTC/TAF, on-demand FTC/TDF, or LA CAB or LEN. However, because his eGFR is less than 60 mL/min, neither daily nor on-demand FTC/TDF would be recommended.

Based on exposure history and his eGFR, both LA CAB and LEN could still be used, but he does not like injections and is not open to an injectable option at this time. Furthermore, LEN would potentially interact with his amlodipine.

These factors leave daily FTC/TAF as an option that suits his exposure history, comorbidities, and current comedications without any potential drug interactions, but he reports infrequent exposures only and does not want to add to his current daily pill burden.

Where does this leave us in terms of PrEP options? Could on-demand FTC/TAF be considered?

There is no randomized clinical trial data evaluating on-demand FTC/TAF dosing for people with chronic kidney disease. However, there are some data that suggest it is both safe and effective.

For example, a pharmacokinetic modeling study in healthy women showed that peripheral blood drug levels of FTC/TAF were higher and persisted for longer compared to FTC/TDF using event-based dosing. These results provide encouraging data that this method should be effective for HIV prevention, at least in theory.

In addition, retrospective data from the UK on PrEP users with an eGFR less than 60 mL/min suggest that event-based dosing of FTC/TAF is safe and effective.

Based on these and other data, the 2025 British HIV Association (BHIVA) guidelines include event-based dosing with FTC/TAF as an option, and essentially state that FTC/TDF and FTC/TAF can be used interchangeably.

Ultimately, based on the available evidence and current guideline recommendations, there is no “perfect” PrEP option for this scenario. However, sometimes it is about finding the “right” PrEP option, rather than the “perfect” one.

In this case, not providing PrEP at all is the least preferable option and will only further contribute to existing disparities. It will be important to engage the patient in a shared decision-making conversation, discussing the available data—and where data are lacking—for each of the different options given his medical history so that he can choose the one that fits best into his lifestyle and with his values.

Your Thoughts
What points would you bring up, or what questions would you ask, in a shared decision-making conversation with this individual about PrEP? Leave a comment to join the discussion!