Week 24 efficacy and safety of TMC114/ritonavir in treatment-experienced HIV patients.
BACKGROUND
Agents for the treatment of HIV-1-infected patients with resistance to current antiretroviral (ART) drugs are needed.


METHODS
TMC114-C202 was a randomized, partially blinded, dose-finding study in treatment-experienced HIV-1-infected patients with one or more primary protease inhibitor (PI) mutations and HIV-1 RNA > 1000 copies/ml. Patients were randomized to receive one of four TMC114 doses given with ritonavir (TMC114/r) or investigator-selected control PI drug(s) (CPI); all received an optimized background regimen. The primary intent-to-treat analysis compared the proportion of patients achieving a >or= 1 log10 copies/ml HIV-1 RNA reduction at week 24 between the treatment arms using the time-to-loss of virological response algorithm.


RESULTS
For 278 patients at baseline, mean HIV-1 RNA was 4.7 log10 copies/ml, median CD4 cell count was 106 cells/mul; HIV-1 isolates had a median of three primary PI mutations and a median fold change in lopinavir susceptibility of 80. Discontinuation rates were 23% for TMC114/r versus 64% for CPI. More patients in each TMC114/r dose group achieved >or= 1.0 log10 copies/ml reduction in HIV-1 RNA than in the CPI group (45-62% versus 14%; P <or= 0.003): patients taking TMC114/r twice daily had the greatest responses. HIV-1 RNA was < 50 copies/ml in 18-39% of TMC114/r patients versus 7% CPI (P < 0.001 for highest dose). Mean CD4 cell count increased by 59-75 versus 12 cells/mul (TMC114/r versus CPI: P <or= 0.005). Overall adverse event rates were similar in both arms, without significant differences among TMC114/r groups.


CONCLUSIONS
TMC114/r treatment resulted in greater virological and immunological responses in ART-experienced patients compared with CPI at 24 weeks.
Haubrich
Richard
R
University of California San Diego, San Diego, CA 92103, USA. rhaubrich@ucsd.edu
Berger
Dan
D
Chiliade
Philippe
P
Colson
Amy
A
Conant
Marcus
M
Gallant
Joel
J
Wilkin
Timothy
T
Nadler
Jeffrey
J
Pierone
Gerald
G
Saag
Michael
M
van Baelen
Ben
B
Lefebvre
Eric
E
D018791:CD4 Lymphocyte Count; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage; D019438:Ritonavir / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019438:Ritonavir