East Bay Getting to Zero

Injectable HIV medications and PrEP

Categories:
Clinical Guides, Data, HIV treatment, PrEP, Prevention

Injectable resources

Latest HIV injectable updates

Check out the slides and info from our East Bay Injectable PrEP Symposium held on February 29, 2024.

We currently have 3 long-acting injectable HIV medications (Cabenuva and Sunlenca) and 1 long-acting injectable HIV PrEP medication (Apretude) that are FDA-approved and available.  

Clinical updates:

  • Injectable ART for people with HIV viremia: The IAS-USA treatment guidelines have been updated to recommend considering long-acting CAB/RPV injectable ART (Cabenuva) with intensive case management services for people with HIV viremia who are unable to take oral ART, have high risk of HIV progression, and have a virus susceptible to both CAB and RPV. 
  • CAB+LEN for people with challenges with adherence on oral ART and resistance mutations: a case series by Gandhi et. al. was published in April 2024 of 34 patients on CAB+LEN +/- RPV at 4 academic centers (UCSF Ward 86, UCSD, Case Western MetroHealth and UPenn:
    • All patients reported challenges with adherence to oral ART.
    • Reasons for CAB+LEN: NNRTI mutations, integrase mutations, high viral loads, continued viremia on CAB/RPV alone
    • 24% were cis/trans female, 42% Black/Af Am, 36% Latinx
    • 94% achieved viral suppression at 8 weeks (47% suppressed at baseline)
    • 71% were on q8wk CAB dosing, though the authors state initially using q4wk dosing “may be prudent pending further study” for patients with adherence challenges.
  • The CROI 2024 conference covering the latest HIV scientific research included more evidence that injectable ARTfrom the LATITUDE trial and the Ward 86 team that CAB/RPV and CAB+LEN injectable ART regimens are effective (and superior) for people with adherence challenges and viremia. More details on our CROI 2024 highlights webpage.
  • Injectable PrEP: Apretude (cabotegravir, or CAB) is a long-acting injectable medication for HIV negative individuals given every 2 months that is >99% effective for preventing HIV sexual transmissions. Apretude is covered by Medi-Cal without a prior authorization.
    • Updates on lab monitoring: Get both HIV RNA and HIV Ag/Ab tests at initiation and every 2-3 months while on CAB-LA PrEP when possible to catch acute infections and seroconversions earlier. Combine HIV RNA+Ag/Ab screening with STD screening every 4 months, hep C screening annually and pregnancy testing as needed.
    • CROI 2024 updates: A CDC study evaluated a large cohort of PrEP users, including 439 people on CAB-LA, and found no conclusive LEVI cases. Meanwhile, the HPTN083 study group found that getting viral loads for people on CAB-LA would have detected some cases earlier. These data combined suggest that viral loads are likely not needed in oral PrEP and may be useful in CAB-LA PrEP if you can get them.
    • Updates on LEVI Syndrome (Long-acting Early Viral Inhibition Syndrome):
      • Seroconversions on CAB-LA PrEP are rare and can be hard to detect, so get both HIV RNAs and Ag/Ab tests every 2-3 months.
      • The HPTN 083 study reported 0.3% cases of HIV infection while on CAB-LA PrEP: 18 out of 2,282 cases total, which is a very very low failure rate. Half had delayed diagnoses due to minimal or no  symptoms and labs that were difficult to interpret: very low RNA/DNA levels and delayed Ab production.
      • If someone seroconverts (positive HIV RNA, DNA or Ag/Ab) while on CAB-LA PrEP, get a genotype including integrase resistance and prescribe a PI-based regimen such as Symtuza as rapid ART. If the genotype doesn’t show integrase resistance, you can consider switching to INSTI regimen if desired.
    • Updates on the “CAB tail” when someone stops CAB-LA PrEP:
      • Cabotegravir has a long half-life and there’s a theoretical risk of resistance if a person seroconverts when the drug levels drop after discontinuation. We have not had documented/known cases of this yet.
      • If someone stops CAB-LA for PrEP, prescribe daily oral F/TDF or F/TAF within 8 weeks after the last CAB injection (2-1-1 could be a reasonable alternative in some situations) and get quarterly HIV RNA and Ag/Ab testing for a year after stopping CAB-LA. 
  • For people coming back into care with a history of injectables: If they have been on Cabenuva (injectable cabotegravir/rilpivirine) and their viral load is detectable, or they have been on Apretude (injectable cabotegravir) for PrEP, use Symtuza for rapid ART and include integrase (INSTI) testing in the genotype. This is to account for the long half-life of these drugs and the risk of resistance when the drug levels drop after discontinuation. If the person was on CAB/RPV and is still undetectable, it would be reasonable to offer them an INSTI-based regimen and monitor viral loads carefully. See updated rapid ART protocols here.

  • Sunlenca (lenacapavir, or LEN) is a long-acting injectable HIV medication in a new class called capsid inhibitors taken every 6 months in combination with other active HIV medications for people who have drug-resistance.

  • Cabenuva (cabotegravir/rilpivirine, or CAB/RPV) is a combination of 2 long-acting injectable HIV medications taken every 1 to 2 months. Cabenuva no longer requires an oral lead-in prior to injection. Study data shows long-term virologic suppression and safety to ~3 years.
    • Check carefully for resistance: Remember to check genotype and ART history carefully, including evaluating baseline transmitted resistance. Since CAB/RPV is a 2-drug regimen, we want to avoid using it alone in people with RPV or CAB resistance. Check for the key CAB/RPV resistance mutations listed at the bottom of page 2 of the W86 protocol. You can also analyze the impact of resistance mutations on the Stanford database. See below for guidance around people with RPV resistance mutations.
    • For people starting injections with viremia:
      • Check viral load every 1-2 months after you start CAB/RPV.
      • We recommend staying with q4-week dosing for 3-6 months and wait for sustained viral load suppression before switching to q8-week dosing.
      • CAB/RPV is effective even for people with viremia and adherence challenges and is non-inferior to bictegravir regimens (Biktarvy), but baseline viremia and NNRTI or INSTI resistance are associated with CAB/RPV failures so watch those starting with viremia closely and avoid using it alone with any baseline resistance.
    • For people with chronic hepatitis B: CAB/RPV is not active against hep B. If CAB/RPV is still the best HIV ART option for them, add oral hep B treatment.
    • Consider injection site options: New data presented at CROI 2023 found that CAB/RPV thigh injections have drug levels equivalent to ventrogluteal and dorsogluteal injections.
    • For people with BMI>30 on CAB/RPV:
      • Data presented at CROI 2023 found lower cabotegravir and rilpivirine concentrations were associated with people with high BMI and people who did not use an oral lead-in. 
      • The ATLAS 2M study also found lower drug concentrations with q8-week dosing compared to Q4-week dosing, though still above the necessary concentration.
      • Here are strategies to consider for people with BMI>30, based on discussion with SF and East Bay HIV clinicians and pharmacists and the updated Ward 86 LAI Protocol:
        • Use an oral ART regimen overlapping with the first CAB/RPV injection for the first 2 weeks.
        • Use a 2-inch needle or longer to inject the medication into muscle.
        • Consider using injection sites where you can best reach muscle, e.g. thigh vs. ventrogluteal vs. dorsogluteal injection sites.
        • Stay on a q4-week dosing schedule for at least 3-6 months with consistent viral load suppression before switching to q8-week dosing. 
        • Be even more cautious in people with BMIs>40 since we do not have data yet for people with BMIs>40 and already know that drug levels are lower for people with BMIs 30-40. Consider not using CAB/RPV if you have good alternatives, or consider using 900/600 mg RPV/CAB dosing q4-weeks, pending further data.
    • Injectables for people with RPV resistance mutations, particularly E138 mutations: Lab data has found that the commonly encountered E138 mutations confer at least partial resistance, so a person with an E138 mutation on CAB/RPV alone will have fewer than 2 active medications and would likely eventually develop resistance. To address this, some patients have been on CAB/RPV + Symtuza, but adherence to oral medications can be challenging or undesirable. For these patients, the East Bay HIV provider network has discussed the option of adding LEN, and then considering stopping Symtuza when patients are stably undetectable (3-6 months) on 2+ fully active medications.

  • East Bay access and coverage updates
    • Sunlenca (lenacapavir) has been a Medi-Cal pharmacy benefit since March 1, 2023, and on the ADAP formulary starting April 25, 2023. Prior authorization is required for ADAP coverage due to its high cost. Sunlenca is available through CVS Specialty Pharmacy.
    • Apretude and Cabenuva is covered by Medi-Cal without a prior authorization, and Cabenuva is covered by ADAP without prior authorization. Walgreens Community, AHF, CVS Specialty and Walgreens Alliance pharmacies have Cabenuva ART and Apretude PrEP available.

Apretude training video from Viiv (manufacturer)

Injectable graphics from NLAAD for community members

(HIV ART in yellow and PrEP in blue)

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