A phase II clinical study of the long-term safety and antiviral activity of enfuvirtide-based antiretroviral therapy.
OBJECTIVE
The primary objective was to determine the long-term safety of the subcutaneous self-administration of enfuvirtide. Secondary objectives included the determination of enfuvirtide pharmacokinetics and antiviral activity and the immunological response to the enfuvirtide-containing regimen.


METHODS
A multicenter 48-week uncontrolled open-label rollover study was conducted on 71 HIV-infected adults recruited from previous enfuvirtide clinical trials. Patients with extensive previous use of protease and reverse transcriptase inhibitors received a twice-daily dose of 50 mg enfuvirtide subcutaneously (45 mg deliverable) combined with two or more antiretroviral drugs selected for each individual, guided by resistance testing and previous treatment history.


RESULTS
The mean baseline plasma HIV-RNA level was 4.81 log(10) copies/ml and the mean CD4 cell count was 134.8 cells/microl. The majority (86.9%) of treatment-emergent adverse events were grade 2 or less in severity. Injection site reactions were common, but no patients discontinued treatment. A mean HIV-RNA change of -1.33 log(10) was achieved within 14 days of treatment initiation. At week 48, approximately one-third of all patients in the intent-to-treat population maintained significant suppression of plasma HIV RNA, with either less than 400 copies/ml or more than a 1.0 log(10) decline from baseline. The mean gain in absolute CD4 cell counts at 48 weeks was 84.9 cells/microl. Trough plasma concentrations of enfuvirtide were consistently higher than target concentrations.


CONCLUSIONS
Self-administration of enfuvirtide is not associated with unexpected toxicities for up to one year, and combined with oral antiretroviral drugs was associated with a significant decrease in HIV RNA and an increase in CD4 cell counts.
Lalezari
Jacob P
JP
Quest Clinical Research, San Francisco, CA 94115, USA. drjay@questclinical.com
Eron
Joseph J
JJ
Carlson
Margrit
M
Cohen
Calvin
C
DeJesus
Edwin
E
Arduino
Roberto C
RC
Gallant
Joel E
JE
Volberding
Paul
P
Murphy
Robert L
RL
Valentine
Fred
F
Nelson
Emily L
EL
Sista
Prakash R
PR
Dusek
Alex
A
Kilby
J Michael
JM
D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D004359:Drug Therapy, Combination; D000077560:Enfuvirtide; D005260:Female; D015700:HIV Envelope Protein gp41 / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood
D019380:Anti-HIV Agents; D015700:HIV Envelope Protein gp41; D010446:Peptide Fragments; D012367:RNA, Viral; D000077560:Enfuvirtide