A randomized, controlled study evaluating an induction treatment strategy in which enfuvirtide was added to an oral, highly active antiretroviral therapy regimen in treatment-experienced patients: the INTENSE study.
OBJECTIVE
The aim of the study was to compare the efficacy and safety of induction with the addition of enfuvirtide to a newly designed oral, highly active antiretroviral therapy (HAART) regimen versus HAART alone followed by a maintenance phase wherein participants were randomized to either continue/discontinue enfuvirtide while maintaining HAART or continue HAART alone (NCT00487188).


METHODS
Participants with HIV-1 RNA >/=1000 copies/mL, CD4 count >/=200 cells/mm(3) and genotype sensitivity score >/=2 (excluding enfuvirtide) were randomized 2:1 to enfuvirtide+HAART or HAART alone and assessed every 4 weeks. Participants achieving <50 copies/mL on two consecutive visits by week 24 entered a maintenance phase wherein those receiving enfuvirtide+HAART underwent another randomization 1:1 to maintain enfuvirtide+HAART or discontinue enfuvirtide; those receiving HAART alone continued their regimen. Virological and immunological endpoints were analysed at weeks 24 and 48.


RESULTS
At 24 weeks, 20/31 (65%) participants in the enfuvirtide+HAART arm versus 8/16 (50%) participants in the HAART arm achieved <50 copies/mL. Median time to achieving <50 copies/mL was 57 versus 141 days in the enfuvirtide+HAART and HAART arms (P = 0.048). Withdrawals were similar between groups. In the maintenance phase, at 48 weeks, 14/19 (74%) in the original enfuvirtide+HAART arm (regardless of second randomization) versus 4/8 (50%) in the HAART arm had <50 copies/mL. During maintenance, there were two virological failures in the enfuvirtide+HAART continuation arm, one in the enfuvirtide discontinuation arm and none in the HAART arm.


CONCLUSIONS
Although limited by small participant numbers, these results suggest that treatment with enfuvirtide added to HAART may be an option for many patients.
Clotet
Bonaventura
B
Hospital Universitari Germans Trias i Pujol and irsiCaixa Foundation, Ctra. de Canyet s/n, 08916 Barcelona, Spain.
Capetti
Amedeo
A
Soto-Ramirez
Luis E
LE
Gatell
Jose M
JM
Rowell
Lucy
L
Salgo
Miklos
M
Schapiro
Jonathan M
JM
D000284:Administration, Oral; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D018791:CD4 Lymphocyte Count; D000077560:Enfuvirtide; D005260:Female; D015700:HIV Envelope Protein gp41 / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D016896:Treatment Outcome; D019562:Viral Load
D019380:Anti-HIV Agents; D015700:HIV Envelope Protein gp41; D010446:Peptide Fragments; D012367:RNA, Viral; D000077560:Enfuvirtide