SWIFT: prospective 48-week study to evaluate efficacy and safety of switching to emtricitabine/tenofovir from lamivudine/abacavir in virologically suppressed HIV-1 infected patients on a boosted protease inhibitor containing antiretroviral regimen.
BACKGROUND
In the United States, emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) is a preferred nucleoside reverse transcriptase inhibitor (NRTI) backbone with lamivudine/abacavir (3TC/ABC) as a commonly used alternative. For patients infected with human immunodeficiency virus (HIV-1) virologically suppressed on a boosted protease inhibitor (PI) + 3TC/ABC regimen, the merits of switching to FTC/TDF as the NRTI backbone are unknown.


METHODS
SWIFT was a prospective, randomized, open-label 48-week study to evaluate efficacy and safety of switching to FTC/TDF. Subjects receiving 3TC/ABC + PI + ritonavir (RTV) with HIV-1 RNA < 200 c/mL ≥3 months were randomized to continue 3TC/ABC or switch to FTC/TDF. The primary endpoint was time to loss of virologic response (TLOVR) with noninferiority measured by delta of 12%. Virologic failure (VF) was defined as confirmed rebound or the last HIV-1 RNA measurement on study drug ≥200 c/mL.


RESULTS
In total, 311 subjects were treated in this study (155 to PI + RTV + FTC/TDF, 156 to PI + RTV + 3TC/ABC). Baseline characteristics were similar between the arms: 85% male, 28% black, median age, 46 years; and median CD4 532 cells/mm(3). By TLOVR through week 48, switching to FTC/TDF was noninferior compared to continued 3TC/ABC (86.4% vs 83.3%, treatment difference 3.0% (95% confidence interval, -5.1% to 11.2%). Fewer subjects on FTC/TDF experienced VF (3 vs 11; P = .034). FTC/TDF showed greater declines in fasting low-density lipoproteins (LDL), total cholesterol (TC), and triglycerides (TG) with significant declines in LDL and TC beginning at week 12 with no TC/HDL ratio change. Switching to FTC/TDF showed improved NCEP thresholds for TC and TG and improved 10-year Framingham TC calculated scores. Decreased estimated glomerular filtration rate [corrected] (eGFR) was observed in both arms with a larger decrease in the FTC/TDF arm.


CONCLUSIONS
Switching to FTC/TDF from 3TC/ABC maintained virologic suppression, had fewer VFs, improved lipid parameters and Framingham scores but decreased eGFR. CLINICALTRIALS.GOV IDENTIFIER: NCT00724711.
Department of Infectious Diseases, University of Miami School of Medicine, Miami, FL 33136, USA. rcampo@med.miami.edu
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R
Campo
E
E
DeJesus
U F
UF
Bredeek
K
K
Henry
H
H
Khanlou
K
K
Logue
C
C
Brinson
P
P
Benson
L
L
Dau
H
H
Wang
K
K
White
J
J
Flaherty
T
T
Fralich
B
B
Guyer
D
D
Piontkowsky
D000225:Adenine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000328:Adult; D000368:Aged; D044966:Anti-Retroviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D015415:Biomarkers / Q000097:blood; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D015224:Dideoxynucleosides / Q000008:administration & dosage* / Q000009:adverse effects; D004338:Drug Combinations; D000068679:Emtricitabine; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D006801:Humans; D053208:Kaplan-Meier Estimate; D019259:Lamivudine / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000008:administration & dosage* / Q000009:adverse effects; D011446:Prospective Studies; D011480:Protease Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D011507:Proteinuria / Q000652:urine; D012306:Risk; D000068698:Tenofovir; D000099227:Abacavir
D000225:Adenine; D044966:Anti-Retroviral Agents; D015415:Biomarkers; D003841:Deoxycytidine; D015224:Dideoxynucleosides; D004338:Drug Combinations; D000068679:Emtricitabine; D019259:Lamivudine; D063065:Organophosphonates; D011480:Protease Inhibitors; D000068698:Tenofovir; C492871:abacavir, lamivudine drug combination; D000099227:Abacavir
3TC/ABC; FTC/TDF; HIV-1; switch; virologic failure