What are the alternatives or management strategies for nausea and vomiting associated with taking Truvada (emtricitabine/tenofovir disoproxil fumarate) on demand for Pre-Exposure Prophylaxis (PrEP)?

Managing Nausea and Vomiting with On-Demand Truvada PrEP

If you are experiencing significant nausea and vomiting with on-demand Truvada (TDF/FTC), you should take the medication with food and consider prophylactic antiemetics, or switch to the alternative formulation Descovy (TAF/FTC), which has a superior gastrointestinal tolerability profile. 1, 2

Understanding the Problem

Gastrointestinal side effects, particularly nausea and vomiting, are common with tenofovir disoproxil fumarate (TDF)-containing regimens, occurring in a substantial proportion of users 1, 3. These symptoms are often severe enough to cause medication discontinuation, which undermines HIV prevention efficacy 1, 3.

Immediate Management Strategies

Non-Pharmacological Approaches (First-Line)

• Take Truvada with food: This simple intervention can significantly reduce gastrointestinal symptoms 1
• Eat smaller, more frequent meals rather than large meals when taking the medication 4
• Stay well-hydrated throughout the day to minimize gastrointestinal distress 1

Pharmacological Interventions

Preemptive antiemetic prescribing is recommended when gastrointestinal side effects are anticipated with antiretroviral regimens 1. Consider:

• Ondansetron (5-HT₃ receptor antagonist): High-certainty evidence shows this reduces vomiting (RR 0.55,95% CI 0.51-0.60) 5. Recommended dose is based on standard antiemetic dosing
• Metoclopramide (dopamine receptor antagonist): Can be used for persistent nausea, though may cause sedation 1
• Prochlorperazine: Another dopamine antagonist option for breakthrough nausea 1

The CDC explicitly recommends preemptive prescribing of antiemetics or antispasmodics for PEP regimens that commonly cause nausea, such as those containing TDF 1.

Switching to an Alternative PrEP Formulation

Descovy (TAF/FTC) as Superior Alternative

Tenofovir alafenamide/emtricitabine (Descovy) demonstrates superior gastrointestinal tolerability compared to Truvada 2. In the DISCOVER trial:

• Both regimens had low discontinuation rates, but TAF/FTC had fewer adverse events leading to discontinuation (1% vs 2%) 2
• TAF/FTC was non-inferior for HIV prevention efficacy (IRR 0.47,95% CI 0.19-1.15) 2
• Participants taking TDF-containing regimens were more likely to report nausea and vomiting severe enough to lead to discontinuation 3

Evidence Supporting the Switch

A study comparing TDF/FTC to zidovudine-based regimens found that patients taking TDF were more likely to report diarrhea or abdominal discomfort, while those on zidovudine reported more nausea and vomiting 3. However, when comparing TAF/FTC directly to TDF/FTC, the newer formulation shows better gastrointestinal tolerability 2.

Over half (56%) of PrEP users who switched from Truvada to Descovy did so based on their doctor's recommendation, with 32% citing perceived improved safety 6.

On-Demand Dosing Considerations

For on-demand PrEP (event-driven dosing), you are taking:

• 2 tablets 2-24 hours before sex
• 1 tablet 24 hours after the first dose
• 1 tablet 48 hours after the first dose

This intermittent high-dose exposure may intensify gastrointestinal symptoms compared to daily dosing. The antiemetic strategies above should be timed with your PrEP doses.

When to Contact Your Provider

You should reach out to your healthcare professional immediately if you experience treatment-limiting tolerability issues 1. Specifically contact them if:

• Vomiting prevents you from keeping the medication down
• Symptoms persist beyond 48-72 hours after each dose
• You are unable to complete the on-demand regimen due to side effects
• Symptoms significantly impact your quality of life

Alternative Regimen Selection

If you have experienced treatment-limiting tolerability with TDF/FTC, an alternative regimen should be prescribed 1. Your options include:

1. Switch to TAF/FTC (Descovy): Superior gastrointestinal tolerability with equivalent efficacy 2
2. Use prophylactic antiemetics with continued TDF/FTC: If switching is not feasible 1
3. Consider daily PrEP instead of on-demand: May reduce peak drug exposure and associated symptoms

Important Caveats

• Do not discontinue PrEP without consulting your provider, as this leaves you unprotected against HIV acquisition 1
• Both TDF/FTC and TAF/FTC are safe and effective when adherence is maintained 2, 7
• The decision to switch should balance cost considerations (generic TDF/FTC is less expensive) against tolerability 6
• Ensure adequate adherence monitoring regardless of which formulation you use, as effectiveness depends on taking the medication as prescribed 7