title: The efficacy of an anti-CD4 monoclonal antibody for HIV-1 treatment.
abstract: The availability of 24 antiretroviral (ARV) drugs within six distinct drug classes has transformed HIV-1 infection (AIDS) into a treatable chronic disease. However, the ability of HIV-1 to develop resistance to multiple classes continues to present challenges to the treatment of many ARV treatment-experienced patients. In this case report, we describe the response to ibalizumab, an investigational CD4-binding monoclonal antibody (mAb), in a patient with advanced immunodeficiency and high-level five-class antiretroviral resistance. After starting an ibalizumab-based salvage regimen, the patient had an approximately 4.0 log(10) reduction in viral load. An inadvertently missed infusion at week 32 led to the rapid loss of virologic response and decreased susceptibility to the remainder of the patient's salvage therapy regimen. Following the reinstitution of ibalizumab, phenotypic and genotypic resistance to ibalizumab was detected. Nonetheless, plasma HIV-1 RNA levels stabilized at ∼2.0 log(10) copies/ml below pre-ibalizumab levels. Continued ARV drug development may yield additional clinical and public health benefits. This report illustrates the promise of mAbs for HIV-1 therapy in highly treatment-experienced patients. Therapeutic mAbs may also have a role in pre-exposure prophylaxis in high-risk uninfected populations and may facilitate directly observed therapy (DOT) if two or more synergistic long acting agents become available.
authors: Kaiser Permanente Medical Care Program - Northern California, San Francisco, 94118, United States. Jeffrey.Fessel@kp.org
authors: W Jeffrey
authors: WJ
authors: Fessel
authors: Brooke
authors: B
authors: Anderson
authors: Stephen E
authors: SE
authors: Follansbee
authors: Mark A
authors: MA
authors: Winters
authors: Stanley T
authors: ST
authors: Lewis
authors: Steven P
authors: SP
authors: Weinheimer
authors: Christos J
authors: CJ
authors: Petropoulos
authors: Robert W
authors: RW
authors: Shafer
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D024882:Drug Resistance, Viral / Q000235:genetics; D023581:HIV Fusion Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects
chemical_list: D000911:Antibodies, Monoclonal; D023581:HIV Fusion Inhibitors; C481504:ibalizumab