Descovy from Gilead Sciences Inc

The FDA has approved Descovy (emtricitabine 200-mg and tenofovir alafenamide 25-mg tablets) for HIV-1 pre-exposure prophylaxis (PrEP). It is indicated to reduce the risk of sexually acquired HIV-1 infection in at-risk adults and adolescents excluding individuals at risk from receptive vaginal sex. Patients must have a negative HIV-1 test immediately before beginning treatment. The approval carries the limitation that when used for PrEP, Descovy is not approved in patients at risk of HIV-1 from receptive vaginal sex because its effectiveness in this population has not been evaluated. Descovy is already approved to treat HIV-1 infection in adults and pediatric patients when used in combination with other antiretroviral agents.¹

PHARMACOLOGY AND PHARMACOKINETICS

Emtricitabine and tenofovir alafenamide are HIV nucleoside analogue reverse transcriptase inhibitors. Emtricitabine reaches maximal plasma concentration 3 hours after oral administration and has a median terminal elimination half-life of 10 hours. Tenofovir alafenamide reaches maximal plasma concentration 1 hour after oral administration. It has a median terminal elimination half-life of 0.51 hour, and its pharmacologically active metabolite, tenofovir diphosphate, has a half-life of 150 to 180 hours.¹

DOSAGE AND ADMINISTRATION

When used for PrEP, the dose of Descovy is 1 tablet once daily, with or without food. It should be used only in patients with a body weight of at least 35 kg, and they should be tested for HIV-1 infection immediately before beginning Descovy, at least every 3 months during its use, and upon diagnosis of a sexually trans- mitted infection. Testing for hepatitis B virus (HBV) infection also should occur before beginning Descovy.

Creatinine clearance, serum creatinine, urine glu- cose, and urine protein should be assessed in all patients before beginning Descovy and during its use, on a clinically appropriate schedule. The medication should not be used in patients with creatinine clearance less than 30 mL/min. Patients with chronic kidney dis- ease should have serum phosphorus assessed, as well.¹

CLINICAL TRIALS

The efficacy and safety of Descovy for PrEP were evaluated in a double-blind, multinational, randomized trial of HIV-seronegative men and transgender women who have sex with men and are at risk of HIV-1 infection. Participants received either once-daily Descovy or Truvada (emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg). The primary efficacy endpoint was the incidence HIV-1 infection per 100 person-years, with a minimum follow-up of 48 weeks. At least 50% of participants had 96 weeks of follow-up. Descovy was found to be noninferior to Truvada in reducing the risk of acquiring HIV-1 infection. Efficacy was strongly correlated to adherence to daily dosing in both treatment groups.^1,2

CONTRAINDICATIONS, WARNINGS, AND PRECAUTIONS

Descovy carries a boxed warning stating that severe acute exacerbations of HBV have been reported in HBV-infected patients who have stopped treatment with medications containing emtricitabine and/or tenofovir disoproxil fumarate and may occur upon discontinuation of Descovy. Hepatic function should be closely monitored for at least several months in these patients, and if appropriate, anti-HBV therapy may be warranted. The boxed warning also states that when Descovy is used for PrEP, patients must be confirmed to be HIV negative immediately prior to beginning treatment and at least every 3 months during use. Drug-resistant HIV-1 variants have been identified with use of emtricitabine and tenofovir disoproxil fumarate for HIV-1 PrEP after undetected acute HIV-1 infection. Descovy should not be initiated for PrEP if signs or symptoms of acute HIV-1 infection are present, unless infection status is confirmed to be negative. When used for PrEP, Descovy is contraindicated in patients with unknown or positive HIV-1 status.

The use of Descovy for PrEP should be part of a comprehensive prevention strategy to reduce the risk of sexually transmitted infections. Patients should be counseled on the importance of adherence to daily medication administration and safer sex practices, including using condoms. New-onset and worsening renal impairment has been reported with the use of tenofovir prodrugs. Immune reconstitution syndrome also has been reported in patients with HIV who are treated with combination antiretroviral therapy, including emtricitabine. Descovy should be discontinued if laboratory findings or symptoms of lactic acidosis or pronounced hepatotoxicity occur. The most common adverse reaction in HIV-1 uninfected adults (>5%) is diarrhea.¹

Monica Holmberg, PharmD, BCPS, earned her PharmD at the University of Connecticut in Storrs and completed an ambulatory care residency at the Phoenix VA Health Care System in Arizona. Her practice has also included pediatrics and inpatient mental health. She lives in Phoenix.

REFERENCES

• Descovy [prescribing information]. Foster City, CA: Gilead Sciences, Inc; 2019. gilead.com/-/media/files/pdfs/medicines/hiv/descovy/descovy_pi.pdf. Accessed October 4, 2019.
• U.S. Food and Drug Administration approves Descovy for HIV pre-exposure prophylaxis (PrEP) [news release]. Foster City, CA: Gilead Sciences Inc; October 3, 2019. gilead.com/news-and-press/press-room/press-releases/2019/10/us-food-and-drug-administration-approves-descovy-for-hiv-preexposure-prophylaxis-prep. Accessed October 4, 2019.