Yeztugo

Treatment of HIV-1

Yeztugo is used to treat human immunodeficiency virus type 1 (HIV-1) in adults. It is specifically intended for people who are heavily treatment-experienced, which means they have taken many different HIV medications in the past that are no longer working to control the virus.

Multi-Drug Resistance

This medication is prescribed when a person's HIV infection is considered multi-drug resistant. This happens when the virus changes or mutates so that standard HIV drugs can no longer stop it from multiplying. Yeztugo provides a new option for those whose current treatment regimens are failing.

Combination Therapy

Yeztugo must be used in combination with other antiretroviral medications; it is not a standalone treatment. When used as part of a complete regimen, the goals of treatment include:

• Reducing viral load: Lowering the amount of HIV in the blood to very low levels.
• Improving immune function: Helping to increase the count of CD4+ cells, which are vital for fighting infections.
• Managing long-term health: Helping to prevent the progression of HIV and reducing the risk of HIV-related complications.

Mechanism of Action

Yeztugo belongs to a class of medications called capsid inhibitors. It works differently than many other HIV treatments by targeting the HIV-1 capsid, which is the protein shell that surrounds and protects the virus's genetic material and the enzymes it needs to multiply.

The medication interferes with the viral life cycle at several distinct stages:

• Nuclear Entry: It prevents the virus from transporting its genetic material into the nucleus of the host cell, a step required for the virus to integrate into the cell's DNA.
• Virus Assembly: It disrupts the process of building new virus particles inside the infected cell.
• Capsid Maturation: It interferes with the formation of the capsid shell in new viruses, resulting in virus particles that are defective and unable to infect other cells.

By blocking these multiple steps, Yeztugo helps lower the amount of HIV in the blood, known as the viral load. Because it uses a unique mechanism to attack the virus, it is particularly useful for individuals whose HIV has developed resistance to other classes of antiretroviral drugs.

Common Side Effects

The most frequently reported side effects of Yeztugo involve reactions where the medication is injected. These symptoms are usually mild to moderate but can last for an extended period. Common side effects include:

• Injection site reactions: Pain, redness, swelling, itching, or a burning sensation at the site of the injection.
• Nodules and induration: Small lumps or hardened areas under the skin at the injection site. These lumps are common and may remain visible or felt for several months.
• Nausea: Feeling sick to the stomach.

Serious Side Effects

In some cases, Yeztugo can cause more severe reactions. You should contact your healthcare provider immediately if you experience any of the following:

• Severe injection site reactions: Signs of a skin infection, such as pus, drainage, extreme warmth, or ulcers at the site where the medicine was given.
• Allergic reactions: Symptoms such as a severe skin rash, hives, swelling of the face, lips, or tongue, or difficulty breathing.
• Immune system changes: A condition called Immune Reconstitution Inflammatory Syndrome (IRIS) can occur, where the immune system reacts strongly to previously hidden infections. This is more common in individuals with a history of advanced HIV infection.

This is not a complete list of all possible side effects. If you notice other symptoms or if your injection site reactions become bothersome or do not improve, consult your doctor or pharmacist.

Serious Infections

Yeztugo is an immunosuppressant that may lower the ability of the immune system to fight infections. This can increase the risk of serious bacterial, fungal, or viral infections that may require hospitalization. Treatment is generally not initiated in individuals with a clinically significant active infection. If a serious infection develops during treatment, the medication may be paused until the infection is resolved.

Tuberculosis Screening

Before starting Yeztugo, patients are evaluated for tuberculosis (TB). If a latent TB infection is identified, treatment for TB is typically started before beginning Yeztugo. Monitoring for signs and symptoms of TB continues throughout the course of therapy.

Malignancies

Because Yeztugo affects the immune system, there is a potential risk for the development of malignancies (cancer). Some patients using ustekinumab products have developed non-melanoma skin cancers. Periodic skin examinations are recommended, particularly for those with risk factors for skin cancer or those who are over the age of 60.

Hypersensitivity Reactions

Serious allergic reactions, including anaphylaxis and angioedema, have occurred with this medication. If a severe reaction happens, the medication is discontinued immediately and medical treatment is initiated.

Posterior Reversible Encephalopathy Syndrome (PRES)

PRES is a rare condition affecting the brain that has been reported with the use of ustekinumab products. Symptoms may include headache, seizures, confusion, or vision loss. If PRES is suspected, the medication is stopped and medical care is sought immediately.

Lung Inflammation

Cases of non-infectious pneumonia, including interstitial pneumonia and eosinophilic pneumonia, have been reported. Symptoms such as a new or worsening cough, shortness of breath, or fever should be monitored closely.

Immunizations

Live vaccines should not be administered while using Yeztugo. It is recommended that patients receive all age-appropriate immunizations before starting therapy. Additionally, infants exposed to Yeztugo in utero should not receive live vaccines for six months after birth.

Pregnancy

There is currently not enough research to determine if Yeztugo is safe to use during pregnancy. It is unknown whether the medication can cause harm to a developing fetus. If you are pregnant or planning to become pregnant, your healthcare provider will help you weigh the benefits of the medication against any potential risks.

Breastfeeding

It is not known if Yeztugo passes into breast milk or if it could affect a nursing child. For individuals with HIV, the standard recommendation is to avoid breastfeeding to prevent transmitting the virus to the infant. If you are taking Yeztugo for HIV prevention, talk to your doctor about whether it is safe to breastfeed while receiving this treatment.

Dosage Forms

Yeztugo is supplied as a sterile, preservative-free solution for injection. It is available in the following delivery formats:

• Subcutaneous Injection: This form is provided in single-dose pre-filled syringes for injection under the skin.
• Intravenous Infusion: This form is provided in single-dose vials for administration into a vein by a healthcare professional.

The dosage and administration method are determined by a healthcare provider based on the patient's weight and the condition being treated.

FDA Approval Status

The U.S. Food and Drug Administration (FDA) approved Yeztugo (emtricitabine and tenofovir alafenamide) on September 23, 2024. It is the first generic version of Descovy to receive FDA approval.

Approved Indications

Yeztugo is approved for HIV-1 pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 infection in adults and adolescents weighing at least 35 kg (77 lbs). It is intended for individuals who are at risk of HIV and have a confirmed negative HIV-1 test result immediately prior to starting the medication.

Boxed Warnings

The FDA-approved labeling for Yeztugo includes a boxed warning, the most serious type of warning, for the following risks:

• HIV-1 Resistance: Yeztugo must only be used by individuals confirmed to be HIV-negative. If the medication is taken by someone with an undiagnosed HIV-1 infection, it may lead to the development of drug-resistant HIV-1 strains, making the infection harder to treat.
• Hepatitis B Exacerbation: Severe, acute flare-ups of hepatitis B virus (HBV) infection have been reported in patients who have both HIV-1 and HBV and stop taking medications containing emtricitabine or tenofovir. Patients with HBV should be closely monitored by a healthcare provider for several months after stopping Yeztugo.

Regulatory Requirements

To ensure safety and effectiveness, the FDA requires that healthcare providers verify an individual's HIV-negative status before prescribing Yeztugo and at least every three months during treatment. This frequent testing is necessary to prevent the use of PrEP in someone who has acquired HIV-1, which could lead to drug resistance.

Factors Affecting Cost

The total cost of Yeztugo can vary based on several factors, including your specific insurance plan and the pharmacy you use. Because this medication is an injection administered by a healthcare professional, there may also be costs associated with the clinic visit and the administration procedure.

Initial vs. Maintenance Costs

The cost for the first year of treatment is typically higher than in following years. This is because the starting phase requires both oral tablets and injections to reach effective levels in the body. Subsequent maintenance years involve only two injections per year.

Financial Assistance

Patients may be able to lower their out-of-pocket expenses through various programs:

• Manufacturer Support: The drug manufacturer may offer copay cards or savings programs for those with commercial insurance to help reduce out-of-pocket costs.
• Patient Assistance Programs: Programs may be available for individuals who are uninsured or meet specific income requirements.
• Insurance Coverage: Most private insurance plans, Medicare, and Medicaid may cover Yeztugo, but the specific copay or coinsurance amount will depend on the individual plan.