TMC125 exerts similar initial antiviral potency as a five-drug, triple class antiretroviral regimen.
OBJECTIVE
TMC125, a next generation, non-nucleoside reverse transcriptase inhibitor (NNRTI), demonstrated a remarkable decline of plasma HIV-1 RNA during a phase IIa study. We compared the initial rate of decline of plasma HIV-1 RNA achieved by TMC125 monotherapy with that of a triple class, five-drug regimen, containing drugs from all three currently licensed classes (zidovudine, lamivudine, abacavir, indinavir and nevirapine).


METHODS
The decline in plasma HIV-1 RNA of 12 HIV-1 infected, antiretroviral (ART) naive patients treated for 1 week with TMC125 monotherapy was compared with that observed in the ERA study (n = 11). The plasma HIV-1 RNA elimination rate constant was calculated based on at least four plasma HIV-1 RNA measurements during the first week of treatment (first-order elimination) and compared using the Student's t test.


RESULTS
Median ages were 23 and 38 years for TMC125 and ERA patients, respectively (P = 0.001), median baseline plasma HIV-1 RNA levels were 4.2 and 4.8 log10 copies/ml (P = 0.001) and median baseline CD4 T-cell counts were 458 x 10(6) and 360 x 10(6) cells/l (P = 0.08). The median plasma HIV-1 RNA elimination rate constant was 0.68/day in TMC125 treated patients, and 0.56/day in ERA participants (P = 0.24). The median decline in plasma HIV-1 RNA after 7 days was 1.92 and 1.76 log10 copies (P = 0.77) and the median increase of CD4 T cells was 119 x 10(6) and 60 x 10(6) cells/l, respectively (P = 0.29).


CONCLUSIONS
Monotherapy with TMC125 in ART-naive, HIV-1-infected individuals resulted in a similar rate of decline of plasma HIV-1 RNA during 1 week of therapy as therapy with a five-drug regimen.
Sankatsing
Sanjay U C
SU
Department of Internal Medicine, Division of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Weverling
Gerrit J
GJ
Peeters
Monika
M
van't Klooster
Gerben
G
Gruzdev
Boris
B
Rakhmanova
Aza
A
Danner
Sven A
SA
Jurriaans
Suzanne
S
Prins
Jan M
JM
Lange
Joep M A
JM
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015224:Dideoxynucleosides / Q000627:therapeutic use; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D015497:HIV-1; D006801:Humans; D019469:Indinavir / Q000627:therapeutic use; D019259:Lamivudine / Q000627:therapeutic use; D008297:Male; D019829:Nevirapine / Q000627:therapeutic use; D009570:Nitriles; D011724:Pyridazines / Q000627:therapeutic use*; D011743:Pyrimidines; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome; D015215:Zidovudine / Q000627:therapeutic use; D000099227:Abacavir
D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D017320:HIV Protease Inhibitors; D019469:Indinavir; D019259:Lamivudine; D019829:Nevirapine; D009570:Nitriles; D011724:Pyridazines; D011743:Pyrimidines; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; D000099227:Abacavir; C451734:etravirine