Sunlenca (Lenacapavir)
First-in-class HIV-1 capsid inhibitor for adults with limited treatment options
Sunlenca (lenacapavir) is a first-in-class HIV-1 capsid inhibitor that targets the viral capsid protein at multiple stages of the HIV lifecycle. It is used in combination with other antiretroviral medicines to treat HIV-1 infection in adults with limited treatment options. The oral tablet form is used as a loading dose before transitioning to subcutaneous injections administered every six months, making it one of the longest-acting antiretroviral treatments available.
Quick Facts: Sunlenca
Key Takeaways
- Sunlenca (lenacapavir) is a first-in-class capsid inhibitor that targets the HIV-1 capsid protein at multiple stages of the viral lifecycle, offering a novel mechanism of action distinct from existing antiretroviral drug classes.
- Treatment begins with an oral tablet loading phase (Days 1, 2, and 8), followed by subcutaneous injections every six months starting on Day 15, providing long-acting viral suppression.
- It is specifically indicated for adults with multidrug-resistant HIV-1 who have limited treatment options because other antiretroviral medicines are not sufficiently effective or suitable.
- Sunlenca must never be combined with strong CYP3A inducers such as rifampicin, carbamazepine, phenytoin, or St. John's wort, as these can dramatically reduce its effectiveness.
- The most common side effect of the tablet form is nausea; injection site reactions are common with the subcutaneous form. Immune reconstitution inflammatory syndrome (IRIS) may occur after treatment initiation.
What Is Sunlenca and What Is It Used For?
Sunlenca contains the active substance lenacapavir, a novel antiretroviral agent that belongs to a new drug class known as capsid inhibitors. Unlike other antiretroviral medicines that target specific viral enzymes (such as reverse transcriptase, integrase, or protease), lenacapavir targets the HIV-1 capsid protein, which is a key structural component of the virus. The capsid is the protein shell that surrounds the viral genetic material and plays essential roles at multiple stages of the HIV replication cycle.
Lenacapavir works by interfering with several critical steps in the HIV lifecycle simultaneously. It disrupts capsid-mediated nuclear uptake of HIV-1 proviral DNA (the process by which viral genetic material enters the cell nucleus), interferes with virus assembly and release from infected cells, and affects capsid core formation in newly produced viral particles. This multifaceted mechanism of action is unique among antiretroviral drugs and provides activity against HIV strains that have developed resistance to other drug classes.
Sunlenca is specifically indicated for use in combination with an optimized background antiretroviral regimen in adults whose HIV-1 infection is not adequately suppressed or who have limited treatment options. This typically includes patients who have developed resistance to multiple classes of antiretroviral drugs, a condition sometimes referred to as multidrug-resistant (MDR) HIV. For these patients, traditional treatment options may be exhausted or severely limited, and lenacapavir offers a new mechanism of action that can help achieve and maintain viral suppression.
The treatment regimen with Sunlenca begins with oral tablets that serve as a loading dose to establish therapeutic drug levels quickly in the body. After the oral loading phase, patients transition to subcutaneous injections that are administered every six months by a healthcare professional. This long-acting dosing schedule is one of the most extended intervals among current antiretroviral treatments, which can improve adherence and reduce the burden of daily oral medication for patients living with HIV.
In clinical trials (the CAPELLA study), lenacapavir demonstrated significant antiviral activity in heavily treatment-experienced adults with multidrug-resistant HIV-1. The treatment reduced the amount of HIV in the body (viral load), which in turn strengthened the immune system and reduced the risk of developing HIV-associated illnesses. This makes Sunlenca an important addition to the antiretroviral toolkit for patients with few remaining treatment options.
What Should You Know Before Taking Sunlenca?
Contraindications
Sunlenca is contraindicated (must not be taken) in the following situations:
- Allergy to lenacapavir or to any of the other ingredients contained in the tablets (listed in the "What Does Sunlenca Contain?" section below). If you experience symptoms of an allergic reaction such as skin rash, swelling of the face or throat, or difficulty breathing, seek immediate medical attention.
- Concurrent use of rifampicin, a medicine used to treat certain bacterial infections including tuberculosis. Rifampicin is a potent inducer of CYP3A and P-glycoprotein, which dramatically reduces lenacapavir blood levels and eliminates its therapeutic effect.
- Concurrent use of carbamazepine or phenytoin, medicines used to prevent seizures in epilepsy. These anticonvulsants are strong enzyme inducers that can reduce lenacapavir to subtherapeutic levels.
- Concurrent use of St. John's wort (Hypericum perforatum), an herbal remedy used for depression and mild anxiety. St. John's wort is a well-known enzyme inducer that can significantly reduce the efficacy of many medicines, including lenacapavir.
If you are taking any of the medicines listed above, do not take Sunlenca. Contact your doctor immediately to discuss alternative treatment options. Combining Sunlenca with these medicines can render the HIV treatment ineffective, potentially leading to viral rebound and the development of drug resistance.
Warnings and Precautions
Before starting treatment with Sunlenca, you should discuss the following with your doctor:
- Severe liver disease: If you have ever had severe liver disease or if blood tests have shown liver function abnormalities, your doctor will need to carefully evaluate whether Sunlenca is appropriate for you. Liver function may affect how the drug is metabolized.
- Immune reconstitution inflammatory syndrome (IRIS): When you start taking HIV medicines, your immune system may become stronger and begin to fight infections that were previously present without obvious symptoms. This can cause inflammation and symptoms that may appear to be new infections. This phenomenon, known as IRIS, is particularly common in patients with advanced HIV disease (AIDS) who have had opportunistic infections. Report any new symptoms of inflammation or infection to your doctor immediately.
- Autoimmune disorders: After starting antiretroviral therapy, autoimmune conditions (where the immune system attacks healthy body tissue) may develop, sometimes several months after beginning treatment. Watch for symptoms such as muscle weakness, weakness that starts in the hands and feet and moves toward the trunk, palpitations, tremors, or hyperactivity, and report them promptly.
Pregnancy and Breastfeeding
If you are pregnant, think you may be pregnant, or are planning to have a baby, talk to your doctor or pharmacist before using Sunlenca. As a precautionary measure, Sunlenca should be avoided during pregnancy unless your doctor specifically determines that the benefits outweigh the potential risks. The effects of lenacapavir on the developing fetus have not been fully characterized in humans, and your doctor will help you weigh the benefits and risks of continuing or changing your antiretroviral regimen.
Breastfeeding is not recommended for women living with HIV, regardless of whether they are taking Sunlenca. HIV can be transmitted to the baby through breast milk. If you are breastfeeding or considering breastfeeding, discuss feeding options with your healthcare provider as soon as possible to ensure the safety of your child.
Use in Children and Adolescents
Sunlenca has not been studied in children and adolescents under 18 years of age. The safety and effectiveness of lenacapavir in this age group are not established, and it should not be given to patients under 18. Clinical trials are ongoing to evaluate the use of lenacapavir in younger populations, and recommendations may be updated as new data become available.
Driving and Operating Machinery
Sunlenca is not expected to affect your ability to drive or use machines. No studies on driving performance have been conducted, but based on the known pharmacological profile and reported side effects, there is no indication that lenacapavir would impair cognitive or motor function.
How Does Sunlenca Interact with Other Drugs?
Lenacapavir is metabolized by CYP3A4 and is a substrate of P-glycoprotein (P-gp) and organic anion transporting polypeptide (OATP) 1B1 and 1B3. It is also a moderate inhibitor of CYP3A and an inhibitor of P-gp, BCRP, OATP1B1, and OATP1B3. These pharmacokinetic properties mean that lenacapavir can both be affected by and affect the blood levels of many other medicines. Always inform your doctor about all medicines you are taking, including prescription, over-the-counter, and herbal products.
Major Interactions (Contraindicated)
The following medicines must never be taken together with Sunlenca, as they can reduce lenacapavir levels to the point where it becomes ineffective against HIV:
| Medicine | Used For | Mechanism | Clinical Effect |
|---|---|---|---|
| Rifampicin | Tuberculosis, certain bacterial infections | Strong CYP3A/P-gp inducer | Dramatically reduces lenacapavir levels; treatment failure |
| Carbamazepine | Epilepsy, seizure prevention | Strong CYP3A inducer | Significantly reduced lenacapavir exposure |
| Phenytoin | Epilepsy, seizure prevention | Strong CYP3A inducer | Significantly reduced lenacapavir exposure |
| St. John's wort | Depression, mild anxiety (herbal) | Strong CYP3A/P-gp inducer | Substantially reduced lenacapavir levels |
Medicines Requiring Caution
The following medicines may interact with Sunlenca and require monitoring, dose adjustment, or clinical consideration. Always discuss these with your doctor before combining with Sunlenca:
| Medicine / Class | Examples | Interaction |
|---|---|---|
| Antibiotics | Rifabutin | Moderate CYP3A inducer; may reduce lenacapavir levels |
| Anticonvulsants | Oxcarbazepine, Phenobarbital | CYP3A inducers; may reduce lenacapavir levels |
| HIV medicines | Atazanavir/cobicistat, Efavirenz, Nevirapine, Tipranavir/ritonavir, Etravirine | Various enzyme effects; may alter lenacapavir or co-administered drug levels |
| Migraine medicines | Dihydroergotamine, Ergotamine | CYP3A substrates; lenacapavir may increase their levels |
| PDE5 inhibitors | Sildenafil, Tadalafil, Vardenafil | CYP3A substrates; increased levels possible; dose adjustment needed |
| Corticosteroids | Dexamethasone, Hydrocortisone/Cortisone | Systemic dexamethasone may induce CYP3A; oral/injected corticosteroid levels may increase |
| Statins | Lovastatin, Simvastatin | CYP3A substrates; increased statin levels; risk of myopathy |
| Cardiac glycosides | Digoxin | P-gp substrate; lenacapavir may increase digoxin levels |
| Sedatives | Midazolam, Triazolam | CYP3A substrates; increased sedative effect possible |
| Anticoagulants | Rivaroxaban, Dabigatran, Edoxaban | P-gp/CYP3A substrates; increased bleeding risk possible |
This is not a complete list of all possible drug interactions. Always tell your doctor or pharmacist about every medicine you are taking, including over-the-counter products and herbal supplements. Do not start or stop any medicine while taking Sunlenca without first consulting your healthcare provider.
What Is the Correct Dosage of Sunlenca?
Sunlenca is always used in combination with other antiretroviral medicines as part of an optimized background regimen chosen by your doctor. The treatment follows a specific loading dose schedule using oral tablets, followed by long-acting subcutaneous injections. Your doctor will inform you about which other medicines you need to take alongside Sunlenca and will schedule your injection appointments.
Adult Dosing Schedule
The standard dosing schedule for Sunlenca in adults is as follows:
| Treatment Day | Dose | Administration | Notes |
|---|---|---|---|
| Day 1 | 600 mg (2 tablets) | Oral, swallowed whole | With or without food |
| Day 2 | 600 mg (2 tablets) | Oral, swallowed whole | With or without food |
| Day 8 | 300 mg (1 tablet) | Oral, swallowed whole | With or without food |
| Day 15 | 927 mg (2 injections) | Subcutaneous injection in abdomen | Administered by healthcare professional |
| Every 6 months | 927 mg (2 injections) | Subcutaneous injection in abdomen | Administered by healthcare professional |
The oral tablet phase serves as a pharmacokinetic lead-in to quickly establish therapeutic drug concentrations in the body before transitioning to the long-acting injectable formulation. The two subcutaneous injections on Day 15 are given simultaneously at two different injection sites in the abdomen (stomach area) by a doctor or nurse. After that, injections are given every six months at a healthcare facility.
Children and Adolescents
Sunlenca is not approved for use in patients under 18 years of age. The safety and pharmacokinetics of lenacapavir have not been established in pediatric populations. Do not give this medicine to children or adolescents.
Elderly Patients
No dose adjustment is required for elderly patients. Clinical data in patients aged 65 and over is limited. Sunlenca should be used with the same dosing schedule as in younger adults, but as with all medicines, elderly patients should be monitored appropriately by their healthcare team.
Missed Dose
It is important not to miss any doses of Sunlenca tablets during the oral loading phase, as this is essential for establishing adequate drug levels before transitioning to injections.
- Missed tablet dose: If you forget to take your tablets, contact your doctor or pharmacist immediately for guidance on how to proceed.
- Vomiting within 3 hours: If you vomit within 3 hours of taking Sunlenca tablets, contact your doctor immediately and take two additional tablets. If you vomit more than 3 hours after taking the tablets, you do not need to take extra tablets; simply continue with your scheduled dosing.
- Missed injection appointment: It is essential to keep your scheduled six-monthly injection appointments. If you think you cannot make your appointment, contact your doctor as soon as possible to discuss your treatment options. Regular injections are crucial for maintaining viral suppression.
Overdose
If you take more Sunlenca tablets than recommended, contact your doctor or pharmacist immediately for advice. Taking more than the prescribed dose may increase the risk of side effects. There is no specific antidote for lenacapavir overdose. Treatment would be supportive, with monitoring of vital signs and observation of clinical status. As lenacapavir has a long half-life and is highly protein-bound, dialysis is unlikely to significantly remove the drug from the body.
Do not stop taking Sunlenca or skip doses without talking to your doctor first. Stopping treatment can allow HIV to multiply rapidly, which may worsen your condition, reduce your immune function, and make future treatment more difficult due to the potential development of drug resistance.
What Are the Side Effects of Sunlenca?
Like all medicines, Sunlenca can cause side effects, although not everybody experiences them. The side effects listed below refer primarily to the oral tablet formulation. The subcutaneous injection form may cause additional injection site reactions. It is important to be aware of potential serious side effects and to report any unusual symptoms to your doctor promptly.
Potentially Serious Side Effects
The following serious side effects require immediate medical attention:
In patients with advanced HIV infection (AIDS) who have previously had opportunistic infections, signs and symptoms of inflammation from previous infections may appear shortly after starting HIV treatment. This is believed to occur because the strengthened immune system begins fighting infections that may have been present without causing noticeable symptoms. Autoimmune disorders (where the immune system attacks healthy tissue) may also develop after starting antiretroviral treatment, sometimes several months later. Watch for: muscle weakness, weakness that begins in the hands and feet and moves toward the trunk, palpitations, tremors, or hyperactivity. Contact your doctor immediately if you notice these or any other symptoms of inflammation or infection.
Side Effect Frequency
Common
May affect up to 1 in 10 people
- Nausea
Not Yet Classified by Frequency
Reported during clinical use; frequency not established from tablet data alone
- Immune reconstitution inflammatory syndrome (IRIS)
- Autoimmune disorders secondary to immune reconstitution
The side effect profile of Sunlenca is still being characterized as clinical experience grows. Because lenacapavir is a relatively new medicine, additional side effects may be identified over time through post-marketing surveillance. It is important to report any suspected side effects to your healthcare provider or national medicines authority, as this contributes to ongoing safety monitoring.
In clinical trials, the overall safety profile of lenacapavir was generally favorable, with most adverse events being mild to moderate in severity. The incidence of treatment discontinuation due to adverse events was low. Long-term safety data continue to be collected through ongoing clinical studies and registries.
If you experience any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed here. You can also report side effects directly to your national medicines regulatory authority. By reporting side effects, you help provide more information on the safety of this medicine.
How Should You Store Sunlenca?
Proper storage of Sunlenca is essential to ensure the medicine remains effective and safe to use throughout its shelf life. Follow these guidelines:
- Keep out of sight and reach of children. Store the medicine in a secure location where children cannot access it.
- Check the expiry date printed on the carton and blister before use. The expiry date refers to the last day of the stated month. Do not use Sunlenca after the expiry date (EXP) printed on the packaging.
- No special temperature requirements. Sunlenca tablets can be stored at normal room temperature. No refrigeration is needed.
- Store in the original packaging to protect from moisture. The tablets are provided in a blister within a foil pouch. The foil pouch contains a silica gel desiccant packet or container that helps keep the tablets dry. This desiccant must remain in the foil pouch and should never be swallowed.
- Disposal: Do not throw away medicines via wastewater or household waste. Ask your pharmacist about how to dispose of medicines that are no longer needed. These measures help protect the environment.
What Does Sunlenca Contain?
Active Substance
The active substance is lenacapavir. Each film-coated tablet contains lenacapavir sodium equivalent to 300 mg of lenacapavir. Lenacapavir sodium is the salt form used in the formulation to enhance the pharmaceutical properties of the tablet.
Inactive Ingredients (Excipients)
Tablet core: Mannitol (E421), microcrystalline cellulose (E460), croscarmellose sodium (E468), copovidone, magnesium stearate (E572), poloxamer.
Film coating: Polyvinyl alcohol (E1203), titanium dioxide (E171), macrogol (E1521), talc (E553b), yellow iron oxide (E172), black iron oxide (E172), red iron oxide (E172).
Appearance and Packaging
Sunlenca film-coated tablets are beige, capsule-shaped, film-coated tablets debossed with "GSI" on one side and "62L" on the other side. The tablets are supplied in a blister containing 5 tablets enclosed by a blister card. The blister is packaged in a foil pouch that contains a silica gel desiccant to protect the tablets from moisture. This medicine contains less than 1 mmol (23 mg) of sodium per tablet, making it essentially sodium-free.
Frequently Asked Questions About Sunlenca
Sunlenca (lenacapavir) is used in combination with other antiretroviral medicines to treat HIV-1 infection in adults who have limited treatment options. This typically means patients whose HIV has developed resistance to multiple other drug classes, or for whom other antiretroviral treatments are not suitable due to intolerance or safety concerns. Lenacapavir belongs to a completely new class of HIV medicines called capsid inhibitors, which work differently from all existing antiretroviral drugs.
Sunlenca is unique in several ways. It is the first and only approved HIV-1 capsid inhibitor, targeting the viral capsid protein rather than the enzymes targeted by other drug classes (reverse transcriptase, protease, integrase). It works at multiple stages of the viral lifecycle simultaneously. Additionally, after an initial oral loading phase, it is administered as a subcutaneous injection every six months, making it one of the longest-acting antiretroviral treatments available. This novel mechanism means it can work against HIV strains resistant to other drug classes.
The most common side effect of Sunlenca tablets is nausea, which may affect up to 1 in 10 people. When given as subcutaneous injections, injection site reactions such as pain, swelling, erythema (redness), and nodules are also common. Immune reconstitution inflammatory syndrome (IRIS) may occur in patients with advanced HIV who start effective antiretroviral therapy. Overall, lenacapavir has been well tolerated in clinical trials, with low rates of treatment discontinuation due to side effects.
Sunlenca has important drug interactions that you must discuss with your doctor. It must never be taken with rifampicin, carbamazepine, phenytoin, or St. John's wort, as these dramatically reduce its effectiveness. Many other medicines including certain HIV drugs, statins, blood thinners, migraine medicines, and sedatives may interact with Sunlenca. Your doctor will review all of your current medications and make any necessary adjustments before starting treatment.
As a precautionary measure, Sunlenca should be avoided during pregnancy unless your doctor specifically determines that the benefits outweigh the potential risks. Limited data are available on the use of lenacapavir in pregnant women. If you are pregnant, think you may be pregnant, or are planning a pregnancy, discuss your HIV treatment options with your healthcare provider. Breastfeeding is not recommended for women living with HIV regardless of their treatment, as HIV can be transmitted through breast milk.
Sunlenca tablets should be stored in their original foil pouch to protect from moisture. No special temperature conditions are required. The silica gel desiccant included in the foil pouch should be kept in the pouch and must not be swallowed. Always keep medicines out of the reach of children and do not use after the expiry date printed on the packaging. Unused tablets should be disposed of through your pharmacy rather than thrown in household waste.
References
This article is based on the following peer-reviewed sources and official medical guidelines:
- European Medicines Agency (EMA). Sunlenca (lenacapavir) - Summary of Product Characteristics. Last updated 2025. Available at: EMA - Sunlenca EPAR
- U.S. Food and Drug Administration (FDA). Sunlenca (lenacapavir) - Prescribing Information. Gilead Sciences, Inc. 2022.
- Segal-Maurer S, DeJesus E, Engel N, et al. Capsid Inhibition with Lenacapavir in Multidrug-Resistant HIV-1 Infection (CAPELLA study). New England Journal of Medicine. 2022;386(19):1793-1803.
- World Health Organization (WHO). Consolidated Guidelines on HIV Prevention, Testing, Treatment, Service Delivery and Monitoring. WHO, 2021.
- European AIDS Clinical Society (EACS). Guidelines for the Clinical Management and Treatment of HIV-infected Adults in Europe. Version 12.0, 2023.
- U.S. Department of Health and Human Services (DHHS). Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV. Updated 2024.
- Dvory-Sobol H, Shaik N, Engelman AN, et al. Lenacapavir: a first-in-class HIV-1 capsid inhibitor. Current Opinion in HIV and AIDS. 2022;17(1):15-21.
- British National Formulary (BNF). Lenacapavir. NICE Evidence Services. 2024.
Medical Editorial Team
This article has been written and reviewed by the iMedic Medical Editorial Team, which includes specialists in infectious diseases, clinical pharmacology, and HIV medicine. All content follows the GRADE evidence framework and is based on the most current international guidelines.
Evidence Level 1A - Based on systematic reviews, randomized controlled trials, and regulatory agency assessments (EMA, FDA). All medical claims are referenced to peer-reviewed sources.
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