Adverse Reactions in Virologically Suppressed Adults

Discontinuation rates due to adverse reactions (ARs) and adverse reaction profile in use of the FTC/TAF backbone + EVG/COBI* or FTC/TAF backbone + third agent


Study 109

Discontinuation rates due to ARs through Week 481
of adults who switched to the FTC/TAF backbone + EVG/COBI* discontinued treatment due to ARs
of adults who remained on their baseline FTC/TDF backbone + third agent discontinued treatment due to ARs

ARs through Week 481
Most common treatment-emergent ARs (all grades) Switched to
FTC/TAF +
EVG/COBI*
(%) (n=959)
Remained on
baseline FTC/TDF +
3rd agent
(%) (n=477)
Upper respiratory tract infection 16 11
Diarrhea 10 9
Nasopharyngitis 9 8
Headache 7 4
Cough 7 5
Syphilis 5 6
Insomnia 5 6
Arthralgia 6 5
Bronchitis 6 5
Depression 4 6
Osteopenia 6 5
Back pain 5 5
Nausea 5 3
Sinusitis 5 5
  • Overall, the safety profile of the FTC/TAF backbone + EVG/COBI* in virologically suppressed adults was similar to that of treatment-naive adults2
    • Common adverse reactions (incidence ≥5%; all grades) in clinical studies of treatment-naive adults were nausea (10%), diarrhea (7%), headache (6%), and fatigue (5%)4
See the Study 109 Study Design

Adverse reactions

  • Most common adverse reaction (incidence ≥10%; all grades) in clinical studies was nausea (10%).

Study 1089

Discontinuation rates due to ARs through Week 483
of adults who switched to the FTC/TAF backbone while maintaining third agent discontinued treatment due to ARs
of adults who remained on the FTC/TDF backbone while maintaining third agent discontinued treatment due to ARs
  • There were no discontinuations of study drug because of renal ARs in the FTC/TAF backbone + third agent group vs 1 such discontinuation in the FTC/TDF backbone + third agent group3
  • Discontinue DESCOVY® in patients who develop clinically significant decreases in renal function or evidence of Fanconi syndrome5

ARs through Week 483

Most common reported ARs (all grades)
Switched to
FTC/TAF +
3rd agent
(%) (n=333)
Remained on
baseline FTC/TDF +
3rd agent
(%) (n=330)
Upper respiratory tract infection 9 14
Diarrhea 9 10
Headache 8 5
Nasopharyngitis 8 6
Cough 6 5
Bronchitis 6 5
Back pain 6 5
Arthralgia 6 3
Fatigue 5 4
Sinusitis 4 7
  • Adults who switched to the FTC/TAF backbone + third agent experienced increased fasting lipid values from baseline, while those remaining on the FTC/TDF backbone + third agent remained stable at Week 48
    • Changes in the total-cholesterol-to-HDL ratio were similar (0.1 for the FTC/TAF backbone + third agent vs 0.0 for the FTC/TDF backbone + third agent)
  • 4% of adults in both groups began lipid-lowering agents during the trial3
See lab abnormalities in treatment-naive adults See the Study 1089
Study Design

Important Safety Information

BOXED WARNING: POST TREATMENT ACUTE EXACERBATION OF HEPATITIS B

  • 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.

Warnings and precautions

  • 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.
  • Bone loss and mineralization defects: Decreases in bone mineral density (BMD) have been reported with the use of tenofovir prodrugs. Consider monitoring BMD in patients with a history of pathologic fracture or risk factors for bone loss. Mineralization defects, including osteomalacia associated with PRT, have been reported with the use of TDF-containing products.

Adverse reactions

  • Most common adverse reaction (incidence ≥10%; all grades) in clinical studies was nausea (10%).

Drug interactions

  • 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 and administration

  • Dosage: Patients 12 years and older who weigh ≥35 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.

Pregnancy and lactation

  • 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 US reference population.
  • Lactation: Women infected with HIV-1 should be instructed not to breastfeed, due to the potential for HIV-1 transmission.

Indication

DESCOVY® is indicated in combination with other antiretroviral (ARV) agents for the treatment of HIV-1 infection in patients 12 years and older.

Limitations of Use:
DESCOVY is not indicated for use as pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 in adults at high risk.

*Administered as an STR.
Multi-tablet regimens included the following third agents: DRV + RTV, ATV + RTV, LPV + RTV, EFV, NVP, RPV, DTG, RAL, or MVC.3,4
Third agents included EVG + COBI (as an STR), EFV (as an STR), ATV + COBI, or ATV + RTV.1,2


References:

  1. Mills A, Arribas JR, Andrade-Villanueva J, et al; for GS-US-292-0109 Team. Switching from tenofovir disoproxil fumarate to tenofovir alafenamide in antiretroviral regimens for virologically suppressed adults with HIV-1 infection: a randomised, active-controlled, multicentre, open-label, phase 3, non-inferiority study. Lancet Infect Dis. 2016;16(1):43-52.
  2. GENVOYA® [package insert]. Foster City, CA: Gilead Sciences, Inc.; 2017.
  3. Gallant JE, Daar ES, Raffi F, et al. Efficacy and safety of tenofovir alafenamide versus tenofovir disoproxil fumarate given as fixed-dose combinations containing emtricitabine as backbones for treatment of HIV-1 infection in virologically suppressed adults: a randomised, double-blind, active-controlled phase 3 trial. Lancet HIV. 2016;3(4):e158-e165.
  4. Data on file. Gilead Sciences, Inc.
  5. DESCOVY [package insert]. Foster City, CA: Gilead Sciences, Inc.; 2017.