Gilead Presents New Findings on Profile of Descovy for Potential Use as HIV Pre-exposure Prophylaxis Compared With Truvada?
- Descovy is not approved for the treatment of chronic hepatitis B virus (HBV) infection and the safety and efficacy of Descovy have not been established in patients coinfected with HIV-1 and HBV. Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HIV-1 and HBV and have discontinued products containing emtricitabine (FTC) and/or tenofovir disoproxil fumarate (TDF), and may occur with discontinuation of Descovy. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue Descovy. If appropriate, initiation of anti-hepatitis B therapy may be warranted.
- Immune reconstitution syndrome, including the occurrence of autoimmune disorders with variable time to onset, has been reported.
- New onset or worsening renal impairment: Cases of acute renal failure and Fanconi syndrome have been reported with the use of tenofovir prodrugs. In clinical trials of FTC and tenofovir alafenamide with elvitegravir and cobicistat, there have been no cases of Fanconi syndrome or proximal renal tubulopathy (PRT). Do not initiate Descovy in 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 Descovy in patients who develop clinically significant decreases in renal function or evidence of Fanconi syndrome. Renal monitoring:?In all patients, monitor CrCl, urine glucose, and urine protein prior to initiating and during therapy. In patients with chronic kidney disease, additionally monitor serum phosphorus.
- Lactic acidosis and severe hepatomegaly with steatosis: Fatal cases have been reported with the use of nucleoside analogs, including FTC and TDF. Discontinue Descovy 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 reaction (incidence =10%; all grades) in clinical studies was nausea (10%).
- Prescribing information: Consult the full prescribing information for Descovy for more information on potentially significant drug interactions, including clinical comments.
- Metabolism: Drugs that inhibit P-gp can increase the concentrations of components of Descovy. Drugs that induce P-gp can decrease the concentrations of components of Descovy, which may lead to loss of efficacy and development of resistance.
- Drugs affecting renal function: Coadministration of Descovy with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of emtricitabine and tenofovir and the risk of adverse reactions.
- Dosage: Patients who weigh =25 kg: 1 tablet taken orally once daily with or without food.
- Renal impairment: Not recommended in patients with CrCl <30 mL/min.
- Testing prior to initiation: Test patients for HBV infection and assess CrCl, urine glucose and urine protein.
- Pediatrics: The safety and effectiveness of Descovy coadministered with an HIV-1 protease inhibitor that is administered with either ritonavir or cobicistat have not been established in pediatric subjects weighing less than 35 kg.
- Pregnancy: There is insufficient human data on the use of Descovy during pregnancy. An Antiretroviral Pregnancy Registry (APR) has been established; available data from the APR for FTC shows no difference in the rates of birth defects compared with a U.S. reference population.
- Lactation: Women infected with HIV-1 should be instructed not to breastfeed, due to the potential for HIV-1 transmission.
- Truvada for PrEP must only be prescribed to individuals 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 PrEP following 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 HBV-infected patients who 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
- Do not use Truvada for PrEP in individuals with unknown or positive HIV status
- Reduce HIV-1 risk:?Truvada for PrEP is not always effective in preventing HIV-1. Use only as part of a comprehensive prevention strategy that includes safer sex practices, regular testing for HIV-1 and other STIs, and counseling on reducing sexual risk behaviors
- Reduce potential for drug resistance:?Truvada for PrEP should only be used in individuals confirmed to be HIV-negative immediately prior to initiation, at least every 3 months while taking Truvada, and upon an STI diagnosis. HIV-1 resistance substitutions may emerge in individuals with undetected HIV-1 infection who are taking only Truvada. Truvada alone is not a complete regimen for treating HIV-1
- HIV antibody tests may not detect acute HIV infection. If recent exposures are suspected or symptoms of acute HIV infection are present (e.g., fever, fatigue, myalgia, skin rash), delay initiating (=1 month) or discontinue use and confirm HIV-negative status with a test approved by?U.S. Food and Drug Administration?(FDA) for the diagnosis of acute HIV infection
- If a screening test indicates possible HIV-1 infection, convert the HIV-1 PrEP regimen to an HIV treatment regimen until HIV-negative status is confirmed.
- Counsel on adherence:?Counsel individuals to strictly adhere to their dosing schedule, as efficacy is strongly correlated with adherence. Some individuals, such as adolescents, may benefit from more frequent visits and counseling.
- New onset or worsening renal impairment:?Cases of acute renal impairment and Fanconi syndrome have been reported with the use of tenofovir disoproxil fumarate (TDF). Truvada is not recommended in individuals with estimated creatinine clearance (CrCl) <60 mL/min. Avoid concurrent or recent use with a nephrotoxic agent. Acute renal failure has been reported after initiation of high dose or multiple NSAIDs in patients at risk for renal dysfunction; consider alternatives to NSAIDs in these patients. Monitor renal function in all patients ? See Dosage and Administration
- Bone effects:?Decreases in bone mineral density (BMD) and mineralization defects, including osteomalacia associated with proximal renal tubulopathy, have been reported with the use of TDF Consider monitoring BMD in patients with a history of pathologic fracture or risk factors for bone loss
- 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 PrEP in 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/voxilaprevir increases 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:?An Antiretroviral Pregnancy Registry (APR) has been established. Available data from observational studies and the APR show no increase in the rate of major birth defects for Truvada compared with a US reference population. Consider HIV prevention methods, including Truvada for PrEP in at-risk 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 individuals with CrCl <60 mL/min. In all patients, assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein on a clinically appropriate schedule. In patients with chronic kidney disease, also assess serum phosphorus
- If clinical symptoms of acute HIV-1 infection are present and recent exposures (<1 month) are suspected, delay initiation for at least 1 month until HIV-negative status is reconfirmed. Alternatively, confirm HIV-negative status with a test cleared by?FDA?to aid in the diagnosis of acute HIV-1 infection
- With HIV-1 infected partner(s), or
- Who engage in sexual activity in a high prevalence area or social network and have additional risk factors, such as: inconsistent or no condom use, diagnosis of sexually transmitted infections (STIs), exchange of sex for commodities, use of illicit drugs or alcohol dependence, incarceration, or sexual partners of unknown HIV status with any of these risk factors
U.S. full Prescribing Information for Descovy and Truvada, including?BOXED WARNINGS, is available at?www.gilead.com
Descovy, Descovy for PrEP, Truvada, Truvada for PrEP and Gilead are trademarks of?Gilead Sciences, Inc.or its related companies.
For more information on?Gilead Sciences, please visit the company?s website at?www.gilead.com, follow Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.
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Source:?Gilead Sciences, Inc. Sung Lee, Investors (650) 524-7792 Ryan McKeel, Media (650) 377-3548