Study Design: Virologically Suppressed Adults

Studies 109 & 1089: Study design and baseline characteristics1-3


Study 109: Phase 3, randomized, open-label, multicenter, international, active-controlled study1,2

Primary endpoint1
Proportion of adults with HIV-1 RNA <50 copies/mL at Week 48 using the FDA snapshot algorithm, with a prespecified non-inferiority margin of 12%


Selected secondary endpoints1
Changes in serum creatinine and lumbar spine and hip BMD at Week 48

  • Stable virologic suppression for at least 6 months, no history of treatment failure, and no known resistance to EVG, COBI, FTC, or TAF were required for study inclusion1,2
  • All adults who received the FTC/TAF backbone + EVG/COBI* switched from 1 of 4 FTC/TDF-based regimens1,2
    • FTC/TDF + EVG/COBI*
    • FTC/TDF + EFV*
    • FTC/TDF + RTV-boosted ATV
    • FTC/TDF + COBI-boosted ATV
Study 109: Selected baseline characteristics1,2
Switched to
FTC/TAF +
EVG/COBI*
(n=959)
Remained on
baseline FTC/TDF +
3rd agent
(n=477)
Median age, years (range) 41 (21-77) 40 (22-69)
Sex
Male (%) 89 90
Female (%) 11 10
Race/ethnicity
White (%) 68 66
Hispanic/Latino ethnicity (%) 26 17
Black (%) 18 21
Asian (%) 6 7
Native Hawaiian (%) 1 <1
Native American (%) 1 <1
HIV-1 RNA <50 copies/mL (n) 943 466
Median CD4+ cell count, cells/µL (range) 675 (520-833) 662 (525-831)
Proteinuria by urine dipstick (any grades) (%) 9 10

Warnings and precautions

  • Immune reconstitution syndrome, including the occurrence of autoimmune disorders with variable time to onset, has been reported.

Study 1089: Phase 3, randomized, double-blind, active-controlled, multicenter study3

Primary endpoint3
Proportion of adults with HIV-1 RNA <50 copies/mL at Week 48 as defined by FDA snapshot algorithm with a prespecified non-inferiority margin of 10%


Selected secondary endpoints3
Percentage change from baseline in hip and lumbar spine BMD, change from baseline in serum creatinine, and change from baseline in CD4+ cell count

  • Adults in the study were virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable regimen containing FTC/TDF and 1 of the protocol-specified third agents: DRV + RTV, ATV + RTV, LPV + RTV, EFV, NVP, RPV, DTG, RAL, or MVC3,4||
Study 1089: Selected baseline characteristics3
Switched to
FTC/TAF +
3rd agent
(n=333)
Remained on
baseline FTC/TDF +
3rd agent
(n=330)
Median age, years (range) 48 (42-54) 49 (42-54)
Sex
Male (%) 86 84
Female (%) 14 16
Race/ethnicity
White (%) 73 77
Black (%) 21 20
Other (%) 6 3
Median CD4+ cell count, cells/µL (range) 663 (505-853) 624 (477-819)
Third agent
Boosted PIs (%)§ 47 45
DRV + RTV (%) 25 25
ATV + RTV (%) 16 15
LPV + RTV (%) 5 5
Other agents (%)§ 53 55
NVP (%) 22 20
RAL (%) 20 22
DTG (%) 8 7
Others (%) 4 5
Data are median (IQR) unless stated otherwise.

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.
Third agents included EVG + COBI (as an STR), EFV (as an STR), ATV + COBI, or ATV + RTV.1,2
Adults remained on the following third agents: DRV + RTV, ATV + RTV, LPV + RTV, EFV, NVP, RPV, DTG, RAL, or MVC.3,4
§Adults on boosted PIs (ATV, DRV, and LPV, all boosted with RTV) who were randomly assigned to switch treatment received a fixed combination of 200 mg FTC with 10 mg TAF; those on other third agents received 200 mg FTC with 25 mg TAF. In the United States, only 1 dose of DESCOVY® (FTC 200 mg/TAF 25 mg) is approved for use with any third agent. Adults who maintained FTC/TDF-based regimens received 200 mg FTC with 300 mg TDF for all regimens.3,5
||EFV and RPV were allowed when administered as individual agents, but not as part of a single-tablet regimen.

ATV, atazanavir; COBI, cobicistat; eGFRCG, estimated glomerular filtration rate (Cockcroft-Gault); EVG, elvitegravir; FTC, emtricitabine; IQR, interquartile range; QD, once daily; RTV, ritonavir; STR, single-tablet regimen.

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.