Gilead Announces Decision Not to Pursue Marketing Authorization for Descovy® for Pre-Exposure Prophylaxis in the European Union

There is no cure for HIV or AIDS.

• Descovyfor PrEPis not indicated in individuals at risk of HIV-1 from receptive vaginal sex because effectiveness in this population has not been evaluated.

• Descovyfor PrEPmust be prescribed only to patients confirmed to be HIV negative immediately prior to initiation and at least every 3 months during use. Drug-resistant HIV-1 variants have been identified with use of emtricitabine/tenofovir disoproxil fumarate.

• (FTC/TDF) for HIV-1 PrEPfollowing undetected acute HIV-1 infection. Do not initiate if signs or symptoms of acute HIV-1 infection are present unless HIV-negative status is confirmed.

• Severe acute exacerbations of hepatitis B have been reported in patients infected with hepatitis B virus (HBV) who discontinued products containing FTC and/or TDF and may occur with discontinuation of Descovy. Closely monitor hepatic function with both clinical and laboratory follow-up for at least several months in patients with HBV who discontinue Descovy. If appropriate, anti-hepatitis B therapy may be warranted.

• Descovyfor PrEPis contraindicated in patients with unknown or positive HIV status.

• Use Descovyfor PrEPto reduce the risk of HIV-1 infection as part of a comprehensive strategy that includes adherence to daily dosing and safer sex practices, including condoms, to reduce the risk of sexually transmitted infections (STIs).

• HIV-1 risk factors:Behavioral, biological, or epidemiologic HIV-1 risk factors may include, but are not limited to: condomlesssex, past or current STIs, self-identified HIV risk, having sexual partners of unknown HIV-1 viremic status, or sexual activity in a high-prevalence area or network.

• Reduce STI risk:Counsel on the use of STI prevention measures (e.g., consistent and correct condom use, knowledge of partner's HIV-1 viremic status, regular testing for STIs).

• Reduce potential for drug resistance: Only prescribe Descovyfor PrEPto patients confirmed to be HIV negative immediately prior to initiation, at least every 3 months while taking Descovy, and upon an STI diagnosis. HIV-1 resistance substitutions may emerge in patients with undetected HIV-1 infection who are taking only Descovybecause Descovyalone is not a complete regimen for treating HIV-1.

• Some HIV tests may not detect acute HIV infection. Prior to initiating Descovyfor PrEP, ask patients about potential recent exposure events. If recent (<1 month) exposures are reported or suspected, or symptoms of acute HIV infection (e.g., fever, fatigue, myalgia, skin rash) are present, confirm HIV-negative status with a test approved by the FDA for use in the diagnosis of acute HIV infection.

• If HIV-1 infection is suspected or if symptoms of acute infection are present while taking Descovyfor PrEP, convert the Descovyfor PrEPregimen to a complete HIV treatment regimen until HIV-negative status is confirmed by a test approved by the FDA for use in the diagnosis of acute HIV infection.

• Counsel on adherence:Counsel patients to strictly adhere to daily dosing, as efficacy is strongly correlated with adherence. Some patients, such as adolescents, may benefit from more frequent visits and counseling.

• New onset or worsening renal impairment: Postmarketingcases of renal impairment, including acute renal failure, proximal renal tubulopathy (PRT), and Fanconi syndrome have been reported with tenofovir alafenamide (TAF)-containing products. Do not initiate Descovyin patients with estimated creatinine clearance (CrCl) <30 mL/min. Patients with impaired renal function and/or taking nephrotoxic agents (including NSAIDs) are at increased risk of renal-related adverse reactions. Discontinue Descovyin patients who develop clinically significant decreases in renal function or evidence of Fanconi syndrome. Monitor renal function in all patients (see Dosage and Administration section).

• Lactic acidosis and severe hepatomegaly with steatosis:Fatal cases have been reported with the use of nucleoside analogs, including FTC and TDF. Discontinue use if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity develop, including hepatomegaly and steatosis in the absence of marked transaminase elevations.

• Most common adverse reactions (≥2%) in the Descovyfor PrEPclinical trial were diarrhea, nausea, headache, fatigue, and abdominal pain.

• Prescribing information:Consult the full Prescribing Information for Descovyfor more information, warnings, and potentially significant drug interactions, including clinical comments.

• Metabolism:Drugs that inhibit P-gpcan increase the concentrations of TAF, a component of Descovy. Drugs that induce P-gpcan decrease the concentrations of TAF, which may lead to loss of efficacy.

• Drugs affecting renal function:Coadministration of Descovywith drugs that reduce renal function or compete for active tubular secretion may increase concentrations of FTC and tenofovir and the risk of adverse reactions.

• Dosage:One tablet taken once daily with or without food.

• HIV screening:Test for HIV-1 infection immediately prior to initiating, at least every 3 months during use, and upon diagnosis of an STI (see Warnings and Precautions section).

• HBV screening:Test for HBV infection prior to or when initiating Descovy.

• Renal impairment and monitoring:Not recommended in patients with creatinine clearance (CrCl) <30 mL/min. Prior to or when initiating Descovy, and during use on a clinically appropriate schedule, assess serum creatinine, CrCl, urine glucose, and urine protein in all patients. In patients with chronic kidney disease, assess serum phosphorus.

TRUVADA FOR PrEP(pre-exposure prophylaxis) is indicated to reduce the risk of sexually acquired HIV-1 in adults and adolescents (≥35 kg) who are at risk for HIV. HIV-1-negative status must be confirmed immediately prior to initiation.

• TRUVADA FOR PrEPmust be prescribed only to patients confirmed to be HIV negative immediately prior to initiation and at least every 3 months during use. Drug-resistant HIV-1 variants have been identified with use of TRUVADA FOR PrEPfollowing undetected acute HIV-1 infection. Do not initiate if signs or symptoms of acute HIV-1 infection are present unless HIV-negative status is confirmed.

• Severe acute exacerbations of hepatitis B virus (HBV) have been reported in patients who have HBV infection and discontinued TRUVADA. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients with HBV after discontinuing TRUVADA. If appropriate, initiation of anti-hepatitis B therapy may be warranted.

• TRUVADA FOR PrEPis contraindicated in patients with unknown or positive HIV status

• Lactic acidosis and severe hepatomegaly with steatosis: Fatal cases have been reported with the use of nucleoside analogs, including TRUVADA. Discontinue use if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity develop, including hepatomegaly and steatosis in the absence of marked transaminase elevations.

• Drug interactions: See Drug Interactions section. Consider the potential for drug interactions prior to and during use of TRUVADA, and monitor for adverse reactions.

• Common adverse reactions(>2% and more frequently than placebo) of TRUVADA FOR PrEPin clinical trials were headache, abdominal pain, and weight loss.

• Prescribing information: Consult the full Prescribing Information for TRUVADA for more information, warnings, and potentially significant drug interactions, including clinical comments.

• Hepatitis C antivirals:Coadministration with ledipasvir/sofosbuvir, sofosbuvir/velpatasvir, or sofosbuvir/velpatasvir/voxilaprevirincreases TDF exposure; monitor for adverse reactions.

• Drugs affecting renal function: Coadministration of TRUVADA with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of emtricitabine and/or tenofovir.

Pregnancy and lactation

• Pregnancy: An Antiretroviral Pregnancy Registry (APR) has been established. Available data from observational studies and the APR show no significant difference in the rate of major birth defects for TRUVADA compared with a US reference population. Consider HIV prevention methods, including TRUVADA FOR PrEP in women due to the potential increased risk of HIV-1 infection during pregnancy and mother-to-child transmission during acute HIV-1 infection.

• Lactation: Emtricitabine and tenofovir have been detected in human milk. Evaluate the benefits and risks of TRUVADA FOR PrEP in breastfeeding women, including the risk of HIV-1 acquisition due to nonadherence, and subsequent mother to child transmission. Health benefits of breastfeeding should be considered along with potential adverse effects of TRUVADA on the child, which are unknown.

• Dosage: One tablet, once daily, with or without food.

• HIV screening:Test for HIV-1 infection prior to initiating and at least every 3 months during treatment.

• HBV screening:Test for HBV infection prior to or when initiating treatment.

• Renal impairment and monitoring:Not recommended in patients with CrCl<60 mL/min. Prior to or when initiating TRUVADA, and during use on a clinically appropriate schedule, assess serum creatinine, CrCl, urine glucose, and urine protein in all patients. In patients with chronic kidney disease, assess serum phosphorus.