Paper # 420
Neurologic and Psychiatric Safety Profile of TMC278 Compared with EFV in Treatment-naive HIV-1+ Patients: ECHO and THRIVE Trials at 48 Weeks
Anthony Mills*1, A Antinori2, B Clotet3, M Fisher4, J Fourie5, G Herrera6, C Hicks7, J Madruga8, S Vanveggel9, and M Stevens9
1Private Practice, Los Angeles, US; 2INMI L Spallanzani, Rome, Italy; 3Fndn irsiCaixa, Hosp Univ Germans Trias i Pujol, Univ Autònoma de Barcelona, Spain; 4Brighton and Sussex Univ Hosp NHS Trust, Brighton, UK; 5Dr J Fourie Med Ctr, KwaZulu-Natal, South Africa; 6Hosp CIMA San Jose, Costa Rica; 7Duke Univ Med Ctr, Durham, NC, US; 8Ctr de Referencia e Treinamento DST/AIDS, Sao Paulo, Brazil; and 9Tibotec BVBA, Beerse, Belgium
Background: At week 48, 2 double-blind, double-dummy
phase 3 trials—ECHO (NCT00540449) and THRIVE (NCT00543725)—in treatment-naive HIV+
adults met their primary objective of non-inferiority of TMC278 to efavirenz
(EFV) in confirmed virologic response. As NNRTI have been associated with
neurologic and psychiatric adverse events, and based on the adverse event
profile in the phase 2B study (TMC278-C204), a pre-planned, pooled phase 3
analysis of these adverse events was performed after 48 weeks.
Methods: Patients received (1:1) TMC278 25 mg once
daily or EFV 600 mg once daily + TDF/FTC (ECHO) or TDF/FTC, AZT/3TC, or ABC/3TC
(THRIVE). Adverse events were recorded at each study visit.
Results: Baseline characteristics (n = 1368) were: 24%
female; 61% Caucasian, 23% black or African American, 13% Asian; 8% hepatitis
B/C co-infection. Prior history of neurologic or psychiatric illness was comparable
in both groups (TMC278 33% vs EFV 31%). The overall incidence of
neuropsychiatric adverse events (any cause) was significantly lower with TMC278
(40%) than EFV (57%) (see the table). Differences in incidence of neurologic
and psychiatric adverse events were most pronounced in the first 4 weeks of
treatment, decreased after 4 to 8 weeks, and were stable to week48, but
remained numerically lower with TMC278 than EFV throughout. Most adverse events
in both groups were DAIDS grade 1 or 2. Incidence of neurologic (TMC278 0.3% vs
EFV 0.1%) and psychiatric (0.7% vs 1.0%, respectively) serious adverse events
and neurologic (0.1% vs 0.7%) and psychiatric (1.5% vs 2.2%) adverse events
leading to discontinuation were low. Patients with a history of neurologic or
psychiatric illness, compared with no history, reported more neurologic adverse
events (TMC278 35% vs 23%, respectively; EFV 49% vs 43%) and psychiatric adverse
events (TMC278 35% vs 21%; EFV 41% vs 26%).
Conclusions: In the ECHO and THRIVE trials, TMC278-treated
patients reported significantly fewer neurologic and psychiatric adverse events
overall, primarily because of lower incidence of dizziness and abnormal dreams
or nightmares, than the EFV-treated patients, particularly during the first 4
weeks of treatment.
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