Clinical updates on HIV PrEP for SF providers

General terms

• CAB: cabotegravir, brand name Apretude
• LEN: lenacapavir, brand name Yeztugo
• LAI: long-acting injectable
• IM: intramuscular
• SC: subcutaneous

Medications

• F/TDF: emtricitabine and tenofovir disoproxil fumarate, brand name Truvada
• F/TAF: emtricitabine and tenofovir alafenamide, brand name Descovy
• FTC/TAF/BIC: emtricitabine, tenofovir alafenamide, and bictegravir; brand name Biktarvy
• DTG: dolutegravir, brand name Tivicay
• TDF: tenofovir disoproxil fumarate
• TAF: tenofovir alafenamide
• FTC: emtricitabine
• 3TC: lamivudine
• INSTI: integrase strand transfer inhibitor

Cabotegravir (CAB)

• Time to protection is not known with certainty. The available evidence suggests 50% of people will achieve protective blood levels 1 day after the first injection, 90% of people 3 days after the first injection, and 95% of people 7 days after the first injection.
• Many experts do not believe overlap of oral PrEP and injectable PrEP is needed. There was no overlap in the studies which showed very high efficacy.
• If your practice is not providing immediate same-day starts on CAB and instead must order CAB from a specialty pharmacy, offer patients an optional overlap of oral Truvada or Descovy while they wait to start CAB. Patients can stop taking Truvada or Descovy anytime between day 1 and day 7 of IM CAB, based on their desired duration of overlap, given the available evidence.

Lenacapavir (LEN)

• Data on time to protective levels are limited, but rapid increases have been observed in plasma concentrations of LEN after the initial oral loading dose and first injection, reaching therapeutic levels within hours after the second oral loading dose on day 2.
• If the second oral loading dose is missed, the time to protection increases to 21 days.
• If both oral loading doses are taken on schedule, many experts do not believe it is necessary to overlap those doses with additional oral PrEP medications. There was no overlap in the studies which showed very high efficacy.
• If your practice is not providing immediate same-day starts on LEN and instead must order LEN from a specialty pharmacy, offer patients an optional overlap of oral Truvada or Descovy while they wait to start LEN. Patients can stop taking Truvada or Descovy the day they receive their first LEN injection.

The CDC has published guidance on HIV testing in the setting of injectable CAB and LEN PrEP. This panel provides additional guidance for San Francisco’s local setting:

At CAB or LEN initiation

• If patient is currently using another form of PrEP without interruption, draw a laboratory blood-based HIV Ag/Ab test (no HIV RNA test needed). The provider and patient may choose to administer the first dose of LEN or CAB while laboratory blood-based HIV Ag/Ab result is pending.
• If patient is not currently using PrEP, draw laboratory blood-based HIV Ag/Ab and HIV RNA tests. Wait for the result of the HIV Ag/Ab result before administering the first dose of LEN or CAB. The HIV RNA test result can still be pending.
  • Using a blood-based HIV rapid test for same-day LEN or CAB administration:
    • The provider and patient may choose to administer the first dose of LEN or CAB while laboratory blood-based HIV Ag/Ab and HIV RNA results are pending by performing a blood-based HIV rapid test, provided there are no signs or symptoms of acute HIV.
  • Same-day LEN or CAB administration without blood-based HIV rapid test:
    • If no rapid test is available that day, the provider and patient may use shared decision-making to consider administering the first dose of LEN or CAB while laboratory blood-based HIV Ag/Ab and HIV RNA results are pending, provided there are no signs or symptoms of acute HIV. One factor to consider is provider and/or patient preference to avoid a gap in protection against HIV, which could happen if the patient must return a different day for the injection.
• As a safeguard, it is recommended to confirm that the patient has a reliable means of being contacted if the laboratory blood-based HIV Ag/Ab or HIV RNA result is positive.

At CAB or LEN continuation injections

• If injection is on time, order a laboratory blood-based HIV Ag/Ab test.
• If injection is late, order both laboratory blood-based HIV Ag/Ab and HIV RNA tests.
  • A CAB injection is late if:
    • It is a 2nd initiation injection and 5 or more weeks have passed since the first injection.
    • It is a continuation injection visit and more than 10 weeks have passed since the last injection.
  • A LEN injection is late if:
    • More than 28 weeks have passed since the last injection and oral LEN bridging was not taken in the interim.

More frequent testing not recommended with LEN

HIV testing is not recommended more often than at each LEN continuation injection. However, the provider and patient can consider performing STI testing every 3 months, and can consider adding HIV testing when doing so.

The patient’s current prescribed and over the counter medications, as well as supplements, herbals, and recreational substances should be reviewed and assessed for potential drug-drug interactions (DDIs). Interactions can be checked using the Liverpool HIV Drug Interactions Checker.

Counsel all LEN patients that DDIs can persist for up to 9 months after the last LEN injection.

DDI counseling needed

• Ketamine: Ketamine concentrations may increase due to inhibition of CYP3A4 by LEN and may increase side-effects associated with ketamine, such as respiratory depression and hallucinations. Patients who use ketamine should be counseled to use caution and that effects could last longer than usual. Patients may consider halving their usual ketamine dose.
• Erectile dysfunction drugs: Concentrations of PDE5 inhibitors (i.e sildenafil, tadalafil) may be increased.
  • For sildenafil: Start at a dose of 25 mg.
  • For tadalafil:
    • For use as needed: no more than tadalafil 10 mg every 72 hours.
    • For once daily use: not to exceed 2.5 mg daily.

DDI counseling not needed

• Fentanyl
• GHB

Injection site options for CAB

• CAB is approved for administration by intramuscular (IM) injection into the buttocks (gluteal muscle).
• The recommended site is the ventrogluteal site (side of the hip/buttock). The dorsogluteal site (upper, outer quadrant of the buttock) is also acceptable.
• Do not inject CAB into other sites, including the thigh, as data show that injection in the thigh yields lower medication levels, which may not be protective.

Injection site options for LEN

• LEN is approved for subcutaneous injection primarily in the abdomen or the thigh.
• Absorption of LEN, safety, and tolerability are also adequate when it is injected in the upper buttocks or back of the upper arm.
• Injection site reactions may be more common with administration in the abdomen compared with the other anatomic sites.

Patients with injectable fillers

• Injectable fillers can be difficult to differentiate from surrounding tissues via exam.
• For patients with injectable fillers in the gluteal area desiring injectable PrEP, offer LEN as a primary regimen, as other anatomical sites are available.
• If the patient prefers CAB instead, provider should consider imaging to differentiate areas with and without fillers present.

Patients with gluteal implants

For patients with implants in the gluteal area desiring injectable PrEP:

• Offer LEN with administration via the abdomen, upper thigh, or back of the upper arm.
• Alternatively, offer an exam to identify areas adjacent to the implant that are safe for CAB or LEN injection. If examination is inconclusive in identifying an area suitable for injection, recommend LEN via the abdomen or upper thigh. If gluteal injection site is still desired for any reason, consult a professional with experience in palpating gluteal implants, or consider imaging to identify the implant’s outline.

At 2nd initiation injection visit

Conduct assessment for PEP if 5 or more weeks have passed since the first injection. This is when protection from CAB begins to wane.

At continuation injection visit

Conduct assessment for PEP if 10 or more weeks have passed since the last injection.

When 10 to 16 weeks have passed since the last injection, this panel recommends using shared decision-making to decide whether to initiate PEP, weighing factors such as time since last injection and estimated efficacy, risk of potential exposure, patient and provider risk tolerance, and patient factors such as willingness or ability to take pills.

• HIV Prevention Trials Network (HPTN) estimates of cabotegravir efficacy based on time since each dose are as follows:
  • 1-8 weeks: 98%
  • 9-10 weeks: 96%
  • 11-12 weeks: 94%
  • 13-14 weeks: 92%
  • 15-16 weeks: 90%

How this guidance differs from the CAB package insert

• The CAB package insert and other manufacturer-created materials state that CAB continuation injections are due 2 months following the last injection, and that a patient is past their on-time window for the next injection once 2 months and 7 days have passed.
• This panel's guidance is in alignment with the package insert as depending on the month, 2 months and 7 days can be up to 10 weeks.
• This panel's guidance differs from the package insert in providing information for shared decision-making for whether to initiate PEP when 10-16 weeks have passed since the last injection.

CAB re-initiation dosing may also be needed

CAB re-initiation dosing (1 injection today and another in 4 weeks) may be needed, whether or not PEP is prescribed. The CAB package insert provides this guidance for when to re-initiate, which calculates in months:

• 2nd initiation injection visit: when 2 or more months have passed since the first injection
• Continuation injection visit: when more than 3 months have passed since the last injection

At continuation injection visits

Conduct assessment for PEP if more than 28 weeks have passed since the last injection. This is when protection from LEN begins to wane.

• LEN re-initiation dosing (2 pills each on day of injection and next day) is also needed if more than 28 weeks have passed since last LEN injection and LEN oral bridging was not used as directed.

If a patient starting LAI PrEP or resuming it after a gap in protection from PrEP has a high-risk exposure and it is too late for PEP:

• Assess the patient for current or recent symptoms of acute HIV.
• Order HIV RNA and HIV Ag/Ab.
• Consult an experienced HIV clinician to make a determination and plan.

This panel generally favors proceeding with CAB or LEN PrEP injection while awaiting HIV RNA result, but determinations should be made on case-by-case basis, particularly if patient has current or recent acute HIV symptoms.

SmartPhrases:

• Charting PrEP patient care: .DPHLAIPrEP
• PrEP patient education tools only: .DPHPrEPEducation

SmartSet:

• LAI PrEP medication and lab ordering: DPH AMB HIV LAI