Factors associated with virological response to etravirine in nonnucleoside reverse transcriptase inhibitor-experienced HIV-1-infected patients.
To identify factors associated with virological response (VR) to an etravirine (ETR)-based regimen, 243 patients previously treated with nonnucleoside reverse transcriptase inhibitors (NNRTIs) were studied. The impact of baseline HIV-1 RNA, CD4 cell count, past NNRTIs used, 57 NNRTI resistance mutations, genotypic sensitivity score (GSS) for nucleoside reverse transcriptase inhibitors (NRTIs) and protease inhibitors (PIs), and the number of new drugs used with ETR for the first time on the VR to an ETR regimen were investigated. Among the 243 patients, the median baseline HIV-1 RNA level was 4.4 log(10) copies/ml (interquartile range [IQR], 3.7 to 4.9) and the median CD4 count was 175 cells/mm(3) (IQR, 69 to 312). Patients had been previously exposed to a median of 6 NRTIs, 1, NNRTI, and 5 PIs. Overall, 82% of patients achieved a VR at month 2, as defined by a decrease of at least 1.5 log(10) copies/ml and/or HIV-1 RNA level of <50 copies/ml. No difference in VR was observed between patients receiving or not a boosted PI in combination with ETR. Factors independently associated with a better VR to ETR were the number of drugs (among enfuvirtide, darunavir, or raltegravir) used for the first time in combination with ETR and the presence of the K103N mutation at baseline. Mutations Y181V and E138A were independently associated with poor VR, whereas no effect of the Y181C on VR was observed. In conclusion, ETR was associated with high response rates in NNRTI-experienced patients in combination with other active drugs regardless of the therapeutic class used.
Marcelin
Anne-Genevieve
AG
Department of Virology, Pitié-Salpêtrière Hospital, 83 Boulevard de l'Hôpital, 75013 Paris, France. anne-genevieve.marcelin@psl.aphp.fr
Flandre
Philippe
P
Descamps
Diane
D
Morand-Joubert
Laurence
L
Charpentier
Charlotte
C
Izopet
Jacques
J
Trabaud
Mary-Anne
MA
Saoudin
Henia
H
Delaugerre
Constance
C
Tamalet
Catherine
C
Cottalorda
Jacqueline
J
Bouvier-Alias
Magali
M
Bettinger
Dominique
D
Dos Santos
Georges
G
Ruffault
Annick
A
Alloui
Chakib
C
Henquell
Cecile
C
Rogez
Sylvie
S
Barin
Francis
F
Signori-Schmuck
Anne
A
Vallet
Sophie
S
Masquelier
Bernard
B
Calvez
Vincent
V
D019380:Anti-HIV Agents / Q000627:therapeutic use*; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008297:Male; D009154:Mutation; D009570:Nitriles; D010802:Phylogeny; D011724:Pyridazines / Q000627:therapeutic use*; D011743:Pyrimidines; D012367:RNA, Viral / Q000096:biosynthesis / Q000235:genetics; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016896:Treatment Outcome
D019380:Anti-HIV Agents; D009570:Nitriles; D011724:Pyridazines; D011743:Pyrimidines; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; C451734:etravirine; D054303:HIV Reverse Transcriptase