Safety of enfuvirtide in combination with an optimized background of antiretrovirals in treatment-experienced HIV-1-infected adults over 48 weeks.
BACKGROUND
Antiretroviral tolerability is a critical factor contributing to treatment outcome. The T-20 Versus Optimized Background Regimen Only (TORO) studies assessed the safety and efficacy of enfuvirtide in treatment-experienced HIV-1-infected patients.


METHODS
A total of 997 patients were randomized at a 2:1 ratio to an optimized background antiretroviral regimen plus enfuvirtide (n = 663) or an optimized background regimen alone (control group; n = 334). Control patients could switch to enfuvirtide on virologic failure.


RESULTS
In total, 26.5% of patients randomized to enfuvirtide and 36.6% to the control group discontinued study treatment before week 48; the percentage of patients withdrawn for safety reasons (including adverse events [AEs], deaths, and laboratory abnormalities) was 14.0% in the enfuvirtide group and 11.6% in the control group. Injection site reactions (ISRs) occurred in 98% of enfuvirtide patients and led to treatment discontinuation in 4.4%. Treatment-related (defined as possibly, probably, or remotely) AE rates per 100 patient-years were lower with enfuvirtide (96.2) than in the control group (149.9); diarrhea, nausea, and fatigue, the most frequently reported AEs, were significantly less frequent with enfuvirtide than in the control group. Pneumonia was significantly more frequent in patients treated with enfuvirtide (6.7 vs. 0.6 events per 100 patient-years), although the incidence was within expected ranges for this population. Lymphadenopathy was also higher in enfuvirtide-treated patients (7.1 vs. 1.2 events per 100 patient-years) for control patients.


CONCLUSIONS
The addition of enfuvirtide to an optimized background regimen does not exacerbate AEs commonly associated with antiretrovirals. ISRs limited treatment in <5% of patients.
Trottier
Benoit
B
Clinique Médicale l'Actuel, Montreal, Quebec, Canada. trottier@lactuel.ca
Walmsley
Sharon
S
Reynes
Jacques
J
Piliero
Peter
P
O'Hearn
Mary
M
Nelson
Mark
M
Montaner
Julio
J
Lazzarin
Adriano
A
Lalezari
Jacob
J
Katlama
Christine
C
Henry
Keith
K
Cooper
David
D
Clotet
Bonaventura
B
Arastéh
Keikawus
K
Delfraissy
Jean-François
JF
Stellbrink
Hans-Jürgen
HJ
Lange
Joep
J
Kuritzkes
Daniel
D
Eron
Joseph J
JJ
Cohen
Calvin
C
Kinchelow
Tosca
T
Bertasso
Anne
A
Labriola-Tompkins
Emily
E
Shikhman
Anna
A
Atkins
Belinda
B
Bourdeau
Laurence
L
Natale
Christopher
C
Hughes
Fiona
F
Chung
Jain
J
Guimaraes
Denise
D
Drobnes
Claude
C
Bader-Weder
Silvia
S
Demasi
Ralph
R
Smiley
Lynn
L
Salgo
Miklos P
MP
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D003967:Diarrhea; D004359:Drug Therapy, Combination; D000077560:Enfuvirtide; D005221:Fatigue; D015700:HIV Envelope Protein gp41 / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D023581:HIV Fusion Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1; D006801:Humans; D008206:Lymphatic Diseases; D009325:Nausea; D010446:Peptide Fragments / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D011014:Pneumonia
D019380:Anti-HIV Agents; D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D010446:Peptide Fragments; D000077560:Enfuvirtide