Resistance Profile

STRIBILD resistance profile through 96 weeks1-6

Analysis of resistance was performed in subjects with virologic failure or HIV-1 RNA concentration >400 copies/mL at study discontinuation:

  • In Study 103, 19/353 (5%) subjects in the STRIBILD group and 16/355 (5%) in the ATV + RTV + FTC/TDF group were analyzed for the presence of resistance. Resistance was detected in 6/19 (32%) subjects taking STRIBILD and 0/16 (0%) taking ATV +RTV + FTC/TDF1-3,6
  • In Study 102, 17/348 (5%) subjects in the STRIBILD group and 23/352 (7%) in the EFV/FTC/TDF group were analyzed for the presence of resistance. Resistance was detected in 10/17 (59%) subjects taking STRIBILD and 10/23 (43%) taking EFV/FTC/TDF4-6

Most common drug resistance mutations by treatment arm (n)


aIn isolates with primary EVG resistance substitutions, additional substitutions in integrase associated with resistance to EVG were H51Y, L68I/V, G70R, 173V, G140C, S153A, and E157Q (pooled analysis).

  • In combined clinical studies, some subjects failed with multiple mutations1
    • In combined clinical studies, one or more resistance mutations to EVG, FTC, and/or TDF was detected in 16/30 (53%) subjects treated with STRIBILD who received at least 8 weeks of treatment, had HIV-RNA >400 copies/mL at week 96, or discontinuation, and had evaluable resistance data
    • In a pooled analysis from both studies, subjects (n=13) who developed EVG resistance also showed susceptibility to FTC (due to the development of the M184V/I substitution)
  • EVG-resistant viruses showed varying degrees of cross-resistance in cell culture to raltegravir
  • STRIBILD-resistant isolates remained susceptible to all NNRTIs and protease inhibitors

Important Safety Information

BOXED WARNING: LACTIC ACIDOSIS/SEVERE HEPATOMEGALY WITH
STEATOSIS and POST TREATMENT ACUTE EXACERBATION OF HEPATITIS B

  • Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs, including tenofovir disoproxil fumarate (tenofovir DF), a component of STRIBILD, in combination with other antiretrovirals.
  • STRIBILD is not approved for the treatment of chronic hepatitis B virus (HBV) infection and the safety and efficacy of STRIBILD have not been established in patients coinfected with HBV and HIV-1. Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HBV and HIV-1 and have discontinued emtricitabine or tenofovir DF, components of STRIBILD. 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 STRIBILD. If appropriate, initiation of anti-hepatitis B therapy may be warranted.

Indication

STRIBILD is indicated as a complete regimen for the treatment of HIV-1 infection in adults who are antiretroviral treatment-naive.

References:

  • STRIBILD [package insert]. Foster City, CA: Gilead Sciences, Inc; 2013.
  • Rockstroh JK, DeJesus E.Henry K, et al; for the GS-236-0103 Study Team. A randomized, double-blind comparison of co-formulated elvitegravir/cobicistat/emtricitabine/tenofovir versus ritonavir-boosted atazanavir plus co-formulated emtridtabine and tenofovir DF for initial treatment of HIV-1infection:analysis of week 96 results. J Acquir Immune Defic Syndr. 2013;62(5):483-486.
  • Rockstroh JK, DeJesus E, Henry K, et al. Elvitegravir/cobicistat/emtricitabine and tenofovir DF (STB) has durable efficacy and differentiated safety compared to atazanavir boosted by ritonavir plus emtricitabine/tenofovir DF in treatment-naïve HIV-1 infected patients: week 96 results. Poster presented at: Eleventh International Congress on Drug Therapy in HIV Infection; November 11-15, 2012; Glasgow, UK. Abstract #0424B.
  • Zolopa A, Sax PE, DeJesus E, et al; for the GS-US-236-0102 Study Team. A randomized double-blind comparison of coformulated elvitegravir/cobicistat/ emtricitabine/ tenofovir disoproxil fumarate versus efavirenz/emtricitabine/tenofovir disoproxil fumarate for initialtreatment of HIV-1infection: analysis of week 96 results. J Acquir Immune Defic Syndr.2013;63(1):96-100.
  • Zolopa A, Gallant JF, Cohen C, et al. Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF (STB) Has Durable Efficacy and Differentiated Safety Compared to Efavirenz/Emtricitabine/Tenofovir DF (ATR) in Treatment-naïve HIV-1 Infected Patients: Week 96 Results. Poster presented at: Eleventh International Congress on Drug Therapy in HIV Infection; November 11-15, 2012; Glasgow, UK. Abstract #0424A.
  • White K, Abram ME, Kulkarni R, Rhee M, Szwarcberg J, Miller MD. Emergent drug resistance from the HI V-1phase 3 elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate studies through week 96. Poster presented at: 20th Conference on Retroviruses and Opportunistic Infections; March 3-6, 2013; Atlanta, GA. Abstract #596. Infection; November 11-15, 2012; Glasgow, UK. Abstract #0424A.

Please see full Prescribing
Information, including
BOXED WARNING

Important Safety Information

Dosage and administration

  • Adult dosage: One tablet taken orally once daily with food.
  • Renal impairment: Do not initiate in patients with CrCl below 70 mL/min. Discontinue in patients with CrCl below 50 mL/min.
  • Hepatic impairment: STRIBILD is not recommended in patients with severe hepatic impairment.
  • Testing prior to initiation: Test patients for HBV infection and document baseline CrCl, urine glucose, and urine protein.
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Important Safety Information

BOXED WARNING: LACTIC ACIDOSIS/SEVERE HEPATOMEGALY WITH
STEATOSIS and POST TREATMENT ACUTE EXACERBATION OF HEPATITIS B

  • Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs, including tenofovir disoproxil fumarate (“tenofovir DF”), a component of STRIBILD, in combination with other antiretrovirals.
  • STRIBILD is not approved for the treatment of chronic hepatitis B virus (HBV) infection and the safety and efficacy of STRIBILD have not been established in patients coinfected with HBV and HIV-1. Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HBV and HIV-1 and have discontinued EMTRIVA or VIREAD, which are components of STRIBILD. 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 STRIBILD. If appropriate, initiation of anti-hepatitis B therapy may be warranted.

Contraindications

  • Coadministration: Do not use with drugs highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events. Do not use with drugs that strongly induce CYP3A as this may lead to a loss of virologic response and possible resistance to STRIBILD. Use with the following drugs is contraindicated: alfuzosin, rifampin, dihydroergotamine, ergotamine, methylergonovine, cisapride, lovastatin, simvastatin, pimozide, sildenafil for pulmonary arterial hypertension, triazolam, oral midazolam, and St. John’s wort.

Warnings and precautions

  • New onset or worsening renal impairment: Cases of acute renal failure and Fanconi syndrome have been reported with the use of tenofovir DF and STRIBILD. Monitor estimated creatinine clearance (CrCl), urine glucose, and urine protein in all patients prior to initiating and during therapy; additionally monitor serum phosphorus in patients with or at risk for renal impairment. Cobicistat may cause modest increases in serum creatinine and modest declines in CrCl without affecting renal glomerular function; patients with an increase in serum creatinine >0.4 mg/dL from baseline should be closely monitored for renal safety. Do not initiate STRIBILD in patients with CrCl below 70 mL/min. Discontinue STRIBILD if CrCl declines below 50 mL/min. Avoid concurrent or recent use with a nephrotoxic agent.
  • Use with other antiretroviral products: STRIBILD is a complete regimen for the treatment of HIV-1 infection. Do not coadminister with other antiretroviral products, including products containing any of the same active components; products containing lamivudine; products containing ritonavir; or with adefovir dipivoxil.
  • Decreases in bone mineral density (BMD) and cases of osteomalacia have been seen in patients treated with tenofovir DF. Consider monitoring BMD in patients with a history of pathologic fracture or risk factors for bone loss.
  • Fat redistribution and accumulation have been observed in patients receiving antiretroviral therapy.
  • Immune reconstitution syndrome, including the occurrence of autoimmune disorders with variable time to onset, has been reported.

Adverse reactions

  • Common adverse drug reactions in clinical studies (incidence ≥5%; all grades) were nausea (16%), diarrhea (12%), abnormal dreams (9%), headache (7%), and fatigue (5%).

Drug interactions

  • CYP3A substrates: STRIBILD can alter the concentration of drugs metabolized by CYP3A or CYP2D6. Do not use with drugs highly dependent on these factors for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening adverse events.
  • CYP3A inducers: Drugs that induce CYP3A can decrease the concentrations of components of STRIBILD. Do not use with drugs that strongly induce CYP3A as this may lead to loss of virologic response and possible resistance to STRIBILD.
  • Antacids: Separate STRIBILD and antacid administration by at least 2 hours.
  • Prescribing information: Consult the full Prescribing Information for STRIBILD for more information on potentially significant drug interactions, including clinical comments.

Dosage and administration

  • Adult dosage: One tablet taken orally once daily with food.
  • Renal impairment: Do not initiate in patients with CrCl below 70 mL/min. Discontinue in patients with CrCl below 50 mL/min.
  • Hepatic impairment: Not recommended in patients with severe hepatic impairment.

Pregnancy and breastfeeding

  • Pregnancy Category B: There are no adequate and well-controlled studies in pregnant women. Use during pregnancy only if the potential benefit justifies the potential risk. An Antiretroviral Pregnancy Registry has been established.
  • Breastfeeding: Emtricitabine and tenofovir have been detected in human milk. Because of both the potential for HIV transmission and the potential for serious adverse reactions in nursing infants, mothers should be instructed not to breastfeed.

Indication

STRIBILD is indicated as a complete regimen for the treatment of HIV-1 infection in adults who are antiretroviral treatment-naive.

Please see full Prescribing Information


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