Enfuvirtide, an HIV-1 fusion inhibitor, for drug-resistant HIV infection in North and South America.
BACKGROUND
The T-20 vs. Optimized Regimen Only Study 1 (TORO 1) was a randomized, open-label, phase 3 study of enfuvirtide (T-20), a human immunodeficiency virus type 1 (HIV-1) fusion inhibitor.


METHODS
Patients from 48 sites in the United States, Canada, Mexico, and Brazil with at least six months of previous treatment with agents in three classes of antiretroviral drugs, resistance to drugs in these classes, or both, and with at least 5000 copies of HIV-1 RNA per milliliter of plasma were randomly assigned in a 2:1 ratio to receive enfuvirtide plus an optimized background regimen of three to five antiretroviral drugs or such a regimen alone (control group). The primary efficacy end point was the change in the plasma HIV-1 RNA level from base line to week 24.


RESULTS
A total of 501 patients underwent randomization, and 491 received at least one dose of study drug and had at least one measurement of plasma HIV-1 RNA after treatment began. The two groups were balanced in terms of the median base-line HIV-1 RNA level (5.2 log10 copies per milliliter in both groups), median CD4+ cell count (75.5 cells per cubic millimeter in the enfuvirtide group, and 87.0 cells per cubic millimeter in the control group), demographic characteristics, and previous antiretroviral therapy. At 24 weeks, the least-squares mean change from base line in the viral load (intention-to-treat, last observation carried forward) was a decrease of 1.696 log10 copies per milliliter in the enfuvirtide group, and a decrease of 0.764 log10 copies per milliliter in the control group (P<0.001). The mean increases in CD4+ cell count were 76 cells per cubic millimeter and 32 cells per cubic millimeter, respectively (P<0.001). Reactions at the site of the injections were reported by 98 percent of patients receiving enfuvirtide. There were more cases of pneumonia in the enfuvirtide group than in the control group.


CONCLUSIONS
The addition of enfuvirtide to an optimized antiretroviral regimen provided significant antiretroviral and immunologic benefit through 24 weeks in patients who had previously received multiple antiretroviral drugs and had multidrug-resistant HIV-1 infection.
Lalezari
Jacob P
JP
Quest Clinical Research, Mount Zion Hospital and the University of California, San Francisco, San Francisco 94115, USA. drjay@questclinical.com
Henry
Keith
K
O'Hearn
Mary
M
Montaner
Julio S G
JS
Piliero
Peter J
PJ
Trottier
Benôit
B
Walmsley
Sharon
S
Cohen
Calvin
C
Kuritzkes
Daniel R
DR
Eron
Joseph J
JJ
Chung
Jain
J
DeMasi
Ralph
R
Donatacci
Lucille
L
Drobnes
Claude
C
Delehanty
John
J
Salgo
Miklos
M
D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use; D001938:Brazil; D018791:CD4 Lymphocyte Count; D024882:Drug Resistance, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D000077560:Enfuvirtide; D005260:Female; D015700:HIV Envelope Protein gp41 / Q000009:adverse effects / Q000627:therapeutic use*; D023581:HIV Fusion Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D009656:North America; D010349:Patient Compliance; D010446:Peptide Fragments / Q000009:adverse effects / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood
D019380:Anti-HIV Agents; D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D010446:Peptide Fragments; D012367:RNA, Viral; D000077560:Enfuvirtide