Sunlenca

Injection site reactions (generally considered mild and transient), nodules (bumps) and indurations (skin thickening). In the CAPELLA study, for Grade 3 and 4 laboratory abnormalities, 5% of participants experienced high blood sugar, 6% experienced excess sugar in urine and 13% experienced low creatinine clearance (eGFR) or high serum creatinine. These observed changes were related to the individual’s diabetes or were either transient or unconfirmed. Nausea occurred in 4% of participants.

Do not take with carbamazepine, eslicarbazepine, oxcarbazepine, phenobarbital or phenytoin; rifampin, rifabutin, or rifapentine; pimozide; amiodarone, disopyramide, quinidine, bosentan, ivabradine, lomitapide, cisapride, flibanserin or St. John’s wort. Start the following medications at the lowest dose, titrate carefully and monitor for safety: dexamethasone (do not take more than 16mg/day), hydrocortisone or cortisone; and lovastatin or simvastatin. Not recommended with ergot derivatives (dihydroergotamine, ergotamine and methylergonovine) or tadalafil (for pulmonary arterial hypertension, or PAH). See package insert for dose recommendations with erectile dysfunction drugs sildenafil and vardenafil. Dose adjustment may be needed for buprenorphine or methadone; initiate these medications by titrating to desired effect but use lowest feasible doses for initiation or maintenance and monitor effects. Coadministration with immunosuppressants such as cyclosporine, everolimus, sirolimus, or tacrolimus will require a dose adjustment for these medications and careful monitoring and dose titration based on drug levels – must be monitored very closely. Carefully monitor the effects of fentanyl and oxycodone; tramadol dose may need to be decreased. Avoid naloxegol (for opioid-induced constipation); if unavoidable, decrease its dose and monitor for adverse reactions. Use with caution with alfuzoson; if coadministration is necessary, monitor blood pressure closely and titrate dose of alfuzosin. Avoid use with beaquiline or quetiapine if possible; if benefits outweigh risks for coadministration, monitor liver function and ECG for QTc prolongation. Use caution with triazolam and oral midazolam (Versed). Use with caution if coadministering with warfarin; monitor INR and titrate warfarin dose as clinically indicated. If giving with the psych medications buspirone, paroxetine, brexpiprazole, iloperidone, lumateperone, lurasidone or trazodone, monitor for side effects and may need to use lower dose of psych medication. Would avoid use with clopidogrel but if coadministration is required, monitor for clopidogrel adverse effects. Would try to avoid coadministration with lidocaine, propafenone, dronedarone, diltiazem, verapamil, and digoxin but if necessary, would monitor closely for adverse effects. Use with caution if coadministering with eplerenone or ranolazine; a dose adjustment of these meds will be necessary if taking at same time as Sunlenca. Use caution if coadministering with colchicine used for gout – will require a dose adjustment and monitoring of colchicine. Okay to take with the antacid famotidine (Pepcid), the cholesterol drug rosuvastatin (Crestor), tenofovir alafenamide (TAF, found in Descovy and other medications), tenofovir DF (TDF, found in Truvada and other medications), HCV medications and the antifungal voriconazole. Other acid-reducing medications can also be used, such as H2 blockers (including Axid, Tagamet and Zantac) and proton pump inhibitors (including Nexium, Prevacid and Prilosec). Certain HIV medications cannot be given with Sunlenca because a drug interaction will render it ineffective: do not coadminister with efavirenz, etravirine, nevirapine, or boosted or unboosted atazanavir; these medications are rarely prescribed today. Tell your provider or pharmacist about all medications, herbals, and supplements you are taking or thinking of taking, prescribed or not, as there may be other drug interactions which are not listed here.

Sunlenca long-acting subcutaneous injection—administered just once every six months—is the first in its drug class. It must be used with other HIV medications as the background therapy. Lenacapavir is highly potent at low doses. Drug efficacy was similar across demographic groups (race, sex at birth, age, and geographic region), CD4 cell count and viral load at study entry, and which background HIV medications were used. Sunlenca is a capsid assembly inhibitor, and inhibits HIV replication by interfering with multiple essential steps of the viral lifecycle. Ultimately, it prevents viral RNA from entering the nucleus of human CD4 T cells, halting virus assembly and protein formation, and inhibiting assembly of new viral particles. As always with HIV therapy, remember that adherence remains important for good results. Adherence may be an issue for some people whose HIV therapy has led to drug resistance—information and support is available. At this time, there aren’t sufficient data to support the initiation of Sunlenca during pregnancy. People who become pregnant while on Sunlenca do not necessarily have to switch to another regimen, but may undergo closer monitoring of viral load. Pregnant individuals can voluntarily enroll in the Antiretroviral Pregnancy Registry through their provider; GO TO apregistry.com.

Dr. Melanie Thompson:

Lenacapavir (LEN) is the only FDA-approved capsid inhibitor and the only HIV drug administered by subcutaneous injection every 6 months. It is only approved (in combination with other HIV therapy) for treatment of multidrug-resistant HIV in individuals whose virus is not responding to their current regimen. The FDA specifies two ways to dose LEN. The first requires oral LEN on the day of injectable dosing and the day after, while the second begins oral LEN dosing on days 1, 2 and 8 before injectable dosing starts on day 15. This allows levels of the drug to build quickly to decrease the possibility of resistance. The most common side effects in clinical trials were gastrointestinal symptoms and injection site reactions that were generally mild/moderate, and sometimes long lasting but tolerable. 

At 2 years, 27 participants (37.5%) in the CAPELLA trial had measurable virus that met criteria for resistance testing and LEN mutations were seen in 14 of these. LEN appears to be a genetically fragile compound, requiring high adherence to background therapy and the use of background drugs with good activity against HIV.  

LEN also is subject to a fair number of drug-drug interactions that can persist for up to 9 months after the last dose. Drugs that decrease LEN levels should not be co-administered because they invite resistance to LEN. These include the HIV medications efavirenz, etravirine, nevirapine, atazanavir/cobicistat and tipranavir + ritonavir (rarely used today), some medications for tuberculosis and seizures, and St. John’s wort. LEN can increase the levels of some drugs, including sildenafil (Viagra), tadalafil, vardenafil, ergot drugs, some steroids and the statins lovastatin and simvastatin, causing side effects that may be dangerous. There are other drugs that may have interactions, so be sure that anyone prescribing drugs for you knows all of the drugs and supplements you take, even those that are over the counter. There are no interactions with gender affirming hormones or oral contraceptives.

The real promise of LEN, however, lies in pairing it with other injectable agents with similar half-lives to make a twice-yearly treatment regimen. Unfortunately, none of our currently approved drugs are ideal partners, but this is an area of active research, so stay tuned! LEN is currently being studied with 2 broadly neutralizing antibodies (bNAbs) given every 6 months and also as an oral weekly regimen with the investigational drug islatravir. Although there are few data, there are anecdotal reports of LEN being given every 6 months with cabotegravir every 1-2 months for people who have no other options, but whose virus retains sensitivity to cabotegravir. This approach should be used with caution until fully evaluated in clinical trials. In addition, LEN is being studied as a single-drug PrEP agent in the PURPOSE series of five trials scattered across the globe and addressing diverse populations. 

Finally, the price. The 2 injections plus 2 or 3 lead-in pills of LEN will cost $42,250 for the first year of treatment, and $39,000 for 2 injections alone thereafter (at $19,500 each.) Therefore, while the monthly average may be somewhat comparable to other ART, a single dose of LEN could come with a whopping co-insurance cost. The Gilead patient support program may help with coverage for those not on government insurance, but co-pay assistance does not apply to those on Medicare/Medicaid. Lenacapvir represents an important advance for HIV treatment, but a step backward in lowering the cost of ART.

Activist Joey Wynn:

Lenacapavir is specifically aimed at heavily-treatment-experienced populations and long-term survivors. Since it was only FDA approved barely over a year ago, the jury is still out. This is another injectable in the long march towards a world of injectables and other long-acting agents. The future is definitely brighter with this new choice available. The jury is still out on this one; oddly, I’ve not heard from anyone on it yet, so I’m not sure how easily accessible it is.