What are the guidelines for using lenacapavir for Pre-Exposure Prophylaxis (PrEP)?

Lenacapavir for HIV Pre-Exposure Prophylaxis (PrEP)

Lenacapavir is a promising twice-yearly injectable PrEP option that has demonstrated superior efficacy compared to daily oral PrEP regimens, but it is not yet FDA-approved for PrEP and should not be used for this indication until regulatory approval. 1

Current Status and Efficacy

Lenacapavir is a first-in-class HIV capsid inhibitor currently under development for HIV prevention as PrEP. Recent clinical trial data shows remarkable efficacy:

• In the PURPOSE 2 trial, twice-yearly subcutaneous lenacapavir demonstrated significantly lower HIV incidence (0.10 per 100 person-years) compared to daily oral emtricitabine/tenofovir disoproxil fumarate (F/TDF) (0.93 per 100 person-years) in cisgender men, transgender women, transgender men, and gender-nonbinary persons 1
• The incidence rate ratio was 0.11 (95% CI, 0.02 to 0.51; P = 0.002) compared to F/TDF, representing an 89% reduction in HIV acquisition risk 1

Current PrEP Guidelines

While lenacapavir shows promise, it is not yet included in current PrEP guidelines. Current approved PrEP options include:

• Daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for all populations at risk for HIV (evidence rating: AIa) 2
• For MSM, on-demand (2-1-1) dosing of TDF/FTC is also recommended (evidence rating: AIa) 2
• Long-acting injectable cabotegravir every 8 weeks is recommended for cisgender men, transgender women, and cisgender women at risk of HIV (evidence rating: AIb) 2, 3

Anticipated Dosing and Administration

Based on clinical trials, the anticipated lenacapavir PrEP regimen would be:

• Subcutaneous injection administered every 26 weeks (twice yearly) 1
• This represents a significant advantage over cabotegravir's every-8-week dosing schedule 3

Safety Profile

In clinical trials, lenacapavir has shown a favorable safety profile:

• Most common side effects are injection-site reactions (erythema, swelling, pain) 1, 4
• In the PURPOSE 2 trial, 1.2% of participants discontinued due to injection-site reactions 1
• No serious adverse events related to lenacapavir treatment were reported in clinical studies 4

Potential Advantages of Lenacapavir for PrEP

1. Extended dosing interval: Twice-yearly administration (compared to daily oral PrEP or every-8-week cabotegravir) 1
2. Improved adherence: Eliminates daily pill burden and associated adherence challenges 2
3. Superior efficacy: Demonstrated better protection than daily oral TDF/FTC in clinical trials 1
4. Novel mechanism: As a capsid inhibitor, it represents a new class of antiretrovirals for prevention 4

Limitations and Considerations

• Not yet approved: Lenacapavir is still investigational for PrEP use and awaiting regulatory approval 5
• Access concerns: Equitable global access will be essential, particularly in low- and middle-income countries 5, 6
• Cost implications: Price thresholds for cost-effectiveness vary by region, from $16.58 in western Kenya to $106.28 in South Africa per dose 6

Future Outlook

The International Antiviral Society-USA panel notes that lenacapavir is being studied for HIV prevention in various populations, including cisgender women and people who inject drugs 2. If approved, it would represent a significant advancement in PrEP options, potentially helping to end new HIV infections globally through its extended dosing interval and high efficacy.

Until regulatory approval, healthcare providers should continue to offer currently approved PrEP options while monitoring developments regarding lenacapavir's status for HIV prevention.