RESUMEN
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 â¼2.0 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.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Inhibidores de Fusión de VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , VIH-1/efectos de los fármacos , Anticuerpos Monoclonales/farmacología , Terapia Antirretroviral Altamente Activa , Recuento de Linfocito CD4 , Farmacorresistencia Viral/genética , Inhibidores de Fusión de VIH/farmacología , Infecciones por VIH/virología , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Resultado del Tratamiento , Carga Viral/efectos de los fármacosRESUMEN
HYPOTHESIS: Matched patients who test positive or negative for human immunodeficiency virus (HIV) who are undergoing comparable operations have similar complication rates and outcomes. DESIGN: A retrospective study of surgical outcomes in HIV-infected and matched HIV-noninfected patients. Baseline information including HIV-related laboratory results, complications, and mortality was collected from printed and electronic records through 12 postoperative months. SETTING: Kaiser Permanente Medical Care Program-Northern California, an integrated health organization with more than 3 million members, including more than 5000 HIV-infected members. PATIENTS: From July 1,1997, through June 30, 2002, HIV-infected members undergoing surgical procedures were matched 1:1 with HIV-noninfected patients undergoing surgical procedures by type, location, and year of surgery as well as by sex and age. Surgical procedures studied included appendectomy, arthrotomy or arthroscopy, bowel resection, cholecystectomy, cardiothoracic procedures, hernia repair, hysterectomy, hip or knee replacement, laparoscopy or laparotomy, and mammoplasty. MAIN OUTCOME MEASURES: Complications and mortality through 12 postoperative months, comparisons between HIV-infected and HIV-noninfected patients using matched-pair analyses, and HIV-infected cohort data were analyzed using the Fisher exact test and logistic regression. RESULTS: Of 332 HIV-infected-HIV-noninfected pairs (mean age, 46.7 years; male sex, 91%), more than 95.0% were followed up through 12 postoperative months or until their deaths. Pairs had similar comorbidities, length of hospital stay, and number of postoperative surgical visits (P>.05, all variables). Among HIV-infected patients, the median years with HIV infection was 8.4 years; median CD4 T-cell count was 379/microL; 61.5% of these patients had an HIV RNA level less than 500 copies per milliliter; and 68% were receiving highly active antiretroviral therapy. Various complications were no more frequent among HIV-infected than in HIV-noninfected patients (11.1% vs 10.2%; P = .79), except for pneumonia (P = .04). There were more deaths within the 12 postoperative months in HIV-infected patients (10/332 vs 2/332; P = .02); 2 patients died 30 days or less after being operated on. Among HIV-infected patients, viral load of 30 000 copies per milliliter or more was associated with increased complications (adjusted odds ratio, 2.95; P = .007), but a CD4 cell count less than 200/muL was not associated with poorer outcomes. CONCLUSIONS: The HIV-infected patients had more incidences of postoperative pneumonia and higher 12-month mortality, although other operative outcomes were comparable for HIV-infected and HIV-noninfected patients. Viral suppression to fewer than 30 000 copies per milliliter reduced surgical complications.