Descovy for HIV-1 Treatment and Prevention in Adults and Children

Descovy is a fixed-dose combination tablet containing emtricitabine and tenofovir alafenamide. It is used both to treat HIV-1 infection in adults, adolescents, and pediatric patients (from 14 kg body weight) and to reduce the risk of acquiring HIV-1 infection through sexual exposure in at-risk adults and adolescents weighing at least 35 kg. Descovy works as part of combination therapy for HIV-1 treatment and as pre-exposure prophylaxis (PrEP) for HIV prevention in specific populations.

Descovy is indicated for:

• Treatment of HIV-1 infection in adults and adolescents weighing at least 35 kg, in combination with other antiretroviral agents.
• Treatment of HIV-1 infection in pediatric patients weighing at least 14 kg to less than 35 kg, in combination with other antiretroviral agents including darunavir with cobicistat (but not with other protease inhibitors requiring CYP3A inhibitors).
• Pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 infection in at-risk adults and adolescents weighing at least 35 kg, except those at risk from receptive vaginal sex, who must confirm HIV-negative status immediately prior to initiation and at least every 3 months during use.

Limitations: Descovy is not approved for PrEP in individuals at risk of HIV-1 from receptive vaginal sex because efficacy in this population has not been evaluated.

emtricitabine; tenofovir alafenamide

Descovy combines two HIV nucleoside analog reverse transcriptase inhibitors (NRTIs): emtricitabine and tenofovir alafenamide. Emtricitabine is a cytidine analog that inhibits HIV reverse transcriptase, thereby preventing viral replication. Tenofovir alafenamide is a prodrug converted inside the body to tenofovir, which inhibits HIV reverse transcriptase by mimicking adenosine monophosphate, further blocking viral replication. Together, these drugs reduce the amount of HIV in the body and help prevent infection.

HIV-1 Treatment

• Adults and adolescents ≥35 kg: One tablet containing 200 mg emtricitabine and 25 mg tenofovir alafenamide orally once daily, with or without food.
• Pediatric patients 25 to <35 kg: One 200 mg/25 mg tablet once daily oral dose with or without food.
• Pediatric patients 14 to <25 kg: One 120 mg/15 mg tablet once daily oral dose with or without food.

HIV-1 Pre-Exposure Prophylaxis (PrEP)

• Adults and adolescents weighing at least 35 kg with confirmed HIV-negative status: One 200 mg/25 mg tablet once daily oral dose, with or without food.

Special Populations and Monitoring

• Assess for hepatitis B virus (HBV) infection before or when starting Descovy.
• Monitor renal function (serum creatinine, creatinine clearance), urine glucose and protein, and serum phosphorus in case of chronic kidney disease at baseline and periodically during therapy.
• Screen for HIV-1 immediately before starting PrEP, then at least every 3 months during use; test for acute HIV infection if recent exposure or symptoms suggestive of acute infection are present.
• Descovy is not recommended for patients with estimated creatinine clearance less than 30 mL/min who are not on chronic hemodialysis. For patients on hemodialysis with clearance below 15 mL/min, give one tablet after dialysis.

Use of Descovy for HIV-1 PrEP is contraindicated in individuals with unknown or positive HIV-1 status.

Boxed Warning

• Hepatitis B exacerbation: Severe acute exacerbations of hepatitis B have been reported after discontinuation of Descovy, especially in patients co-infected with HBV. Monitor hepatic function with clinical and laboratory follow-up for several months after stopping treatment; consider anti-HBV therapy if warranted.
• HIV-1 resistance risk in PrEP: Descovy for HIV-1 PrEP must only be prescribed to individuals confirmed HIV-negative immediately before starting and at least every 3 months during use. Use in undiagnosed acute HIV-1 infection can lead to drug-resistant HIV-1 variants.

Other Important Warnings and Precautions

• Immune reconstitution syndrome: May occur after initiation of HIV treatment and require additional evaluation and treatment.
• Renal impairment: Monitor renal function regularly. Descovy is not recommended with creatinine clearance 15–30 mL/min or less than 15 mL/min unless on hemodialysis.
• Lactic acidosis and severe hepatomegaly with steatosis: A rare but serious adverse effect of nucleoside analogs including emtricitabine. Suspend treatment if symptoms or laboratory signs appear.
• Comprehensive risk reduction counseling: When using Descovy for PrEP, counsel patients on adherence to daily dosing and safer sex practices to reduce risk of HIV and other sexually transmitted infections.

In HIV-infected adults receiving Descovy with other antiretrovirals, the most common adverse reaction (≥10%) was nausea. In pediatric patients and those with HIV-1 infection, the adverse effect profile was similar to adults.

In HIV-negative adults using Descovy for PrEP, the most common adverse reaction (≥5%) was diarrhea. Other symptoms occurring in ≥2% include nausea, headache, fatigue, and abdominal pain.

Serious adverse events include acute renal failure, proximal renal tubulopathy, Fanconi syndrome, angioedema, urticaria, and rash.

Laboratory changes include mild increases in serum creatinine and lipid levels, as well as changes in bone mineral density, though long-term clinical significance is unknown.

Descovy contains tenofovir alafenamide (TAF), a substrate of P-glycoprotein (P-gp) and BCRP transporters. Drugs that induce P-gp (e.g., rifampin, carbamazepine, phenobarbital, St. John’s wort) may decrease TAF plasma concentrations and reduce effectiveness, so coadministration is not recommended.

Conversely, inhibitors of P-gp and BCRP may increase TAF levels.

Coadministration with some protease inhibitors may alter TAF levels; atazanavir/cobicistat is not recommended in pediatric patients weighing 14 to less than 35 kg.

Because emtricitabine and tenofovir are primarily renally excreted, coadministration with drugs that reduce renal function or compete for active tubular secretion (e.g., aminoglycosides, certain antivirals like acyclovir, cidofovir, and NSAIDs) may increase risk of toxicity.

No significant clinically relevant interactions have been observed with several common antiretroviral and other drugs such as darunavir with ritonavir or cobicistat, dolutegravir, efavirenz, ketoconazole, methadone, and sertraline.

Lactation

Emtricitabine, tenofovir alafenamide, and tenofovir are present in human milk. Data have not reported adverse effects on breastfed infants, but potential risks include HIV transmission, development of viral resistance if infants are infected, and possible adverse reactions similar to those in adults.