Antiretroviral activity of the anti-CD4 monoclonal antibody TNX-355 in patients infected with HIV type 1.
BACKGROUND
We wished to determine the safety and anti-human immunodeficiency virus (HIV) type 1 activity of single doses of TNX-355, a humanized IgG4 anti-CD4 monoclonal antibody with potent activity against HIV-1 in vitro, in HIV-infected subjects.


METHODS
Sequential cohorts of 6 HIV-1-infected subjects each received infusions of TNX-355. Data included plasma HIV-1 RNA level, CD4+ T cell count, TNX-355 coating of CD4+ T cells, and serum TNX-355 levels.


RESULTS
Dose-related reductions in plasma HIV-1 RNA loads correlated with complete CD4+ T cell coating by TNX-355. Peak median decreases in plasma HIV-1 RNA loads were 0.56, 1.33, and 1.11 log10 copies/mL and occurred on days 4-7, 14, and 21 for the 3.0, 10, and 25 mg/kg doses, respectively. Dose-dependent increases in CD4+ T cell count occurred within 24 h of dosing.


CONCLUSIONS
Single doses of TNX-355 reduced plasma HIV-1 RNA loads and increased CD4+ T cell counts in HIV-infected subjects. The further assessment of therapeutic potential awaits data from longer-duration trials.
Kuritzkes
Daniel R
DR
Division of Infectious Diseases, University of Colorado Health Sciences Center, Denver, USA. dkuritzkes@partners.org
Jacobson
Jeffrey
J
Powderly
William G
WG
Godofsky
Eliot
E
DeJesus
Edwin
E
Haas
Frances
F
Reimann
Keith A
KA
Larson
Jeffrey L
JL
Yarbough
Patrice O
PO
Curt
Valentin
V
Shanahan
William R
WR
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000628:therapy* / Q000821:virology; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019540:Area Under Curve; D015704:CD4 Antigens / Q000276:immunology*; D018791:CD4 Lymphocyte Count; D005260:Female; D015497:HIV-1; D006801:Humans; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood
D019380:Anti-HIV Agents; D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D012367:RNA, Viral