Prescribing Information
Efficacy and Resistance

Efficacy and Resistance

TRUVADA® (emtricitabine/tenofovir disoproxil fumarate) efficacy

INDICATION

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, when used in combination with safer sex practices. HIV-negative status must be confirmed immediately prior to initiation


No cases of drug resistance were observed among individuals who were HIV-1 negative at baseline


To minimize the risk of resistance, TRUVADA FOR PrEP® should only be prescribed to individuals confirmed to be HIV-1 negative


Of the individuals who became infected with HIV-1 after initiating TRUVADA FOR PrEP, no cases of resistance to the components of TRUVADA were identified at the time of HIV-1 seroconversion in two pivotal trials.1-3

Individuals Who Became HIV Positive During the Study1

      HIV+(Subjects, n) HIV+ WITH RESISTANCE(Subjects, n)
Partners PrEP Trial PLACEBO 51 0
TRUVADA 12 0
iPrEx Trial PLACEBO 83 0
TRUVADA 48 0

Of the individuals who had unrecognized/acute HIV-1 infection at the time of TRUVADA FOR PrEP initiation, resistance to the components of TRUVADA was observed in two pivotal trials.1-3

Individuals With Unrecognized/Acute HIV Infection at Baseline1

      HIV+(Subjects, n) HIV+ WITH RESISTANCE(Subjects, n)
Partners PrEP Trial PLACEBO 6 0
TRUVADA 3  1*
iPrEx Trial PLACEBO 8  1*
TRUVADA 2  2*

*M184V/I.

  • While using TRUVADA FOR PrEP, HIV-1 screening tests should be repeated at least every 3 months and upon diagnosis of any STIs. Individuals should be counseled to adhere to the recommended TRUVADA dosing schedule. Some individuals, such as adolescents, may benefit from more frequent visits and counseling1
  • TRUVADA FOR PrEP should only be prescribed to individuals who are confirmed to be HIV-1 negative immediately prior to initial use and who do not have signs or symptoms consistent with acute HIV infection1
Learn about the safety profile of TRUVADA FOR PrEP

INDICATION

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, when used in combination with safer sex practices. HIV-negative status must be confirmed immediately prior to initiation

  • 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 the FDA to aid in the diagnosis of acute HIV-1 infection

Individuals at risk for sexually acquired HIV-1 may include those:

  • 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

IMPORTANT SAFETY INFORMATION

BOXED WARNING: RISK OF DRUG RESISTANCE WITH USE OF TRUVADA FOR PrEP IN UNDIAGNOSED EARLY HIV-1 INFECTION and POST TREATMENT ACUTE EXACERBATION OF HEPATITIS B

  • 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

Contraindications

  • TRUVADA FOR PrEP is contraindicated in individuals with unknown or positive HIV status

Warnings and precautions: Comprehensive risk reduction strategies

  • 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 the 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

IMPORTANT SAFETY INFORMATION (cont'd)

Warnings and precautions

  • 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 section
  • 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

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

Drug interactions

  • 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 and lactation

  • 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 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 and administration

  • 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

References: 1. TRUVADA [package insert]. Foster City, CA: Gilead Sciences, Inc.; 2018. 2. Baeten JM, Donnell D, Ndase P, et al. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N Engl J Med. 2012;367(5):399-410. 3. Grant RM, Lama JR, Anderson PL, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med. 2010;363(27):2587-2599.

Tap for Important Safety Information, including BOXED WARNING on the risk of drug resistance with TRUVADA FOR PrEP in undiagnosed early HIV-1 infection and post-treatment acute exacerbation of hepatitis B.