RESUMEN
Gene transfer has potential as a once-only treatment that reduces viral load, preserves the immune system and avoids lifetime highly active antiretroviral therapy. This study, which is to our knowledge the first randomized, double-blind, placebo-controlled, phase 2 cell-delivered gene transfer clinical trial, was conducted in 74 HIV-1-infected adults who received a tat-vpr-specific anti-HIV ribozyme (OZ1) or placebo delivered in autologous CD34+ hematopoietic progenitor cells. There were no OZ1-related adverse events. There was no statistically significant difference in viral load between the OZ1 and placebo group at the primary end point (average at weeks 47 and 48), but time-weighted areas under the curve from weeks 40-48 and 40-100 were significantly lower in the OZ1 group. Throughout the 100 weeks, CD4+ lymphocyte counts were higher in the OZ1 group. This study indicates that cell-delivered gene transfer is safe and biologically active in individuals with HIV and can be developed as a conventional therapeutic product.
Asunto(s)
Antígenos CD34/inmunología , Terapia Genética , Infecciones por VIH/terapia , VIH-1/genética , ARN Catalítico/genética , Adulto , Secuencia de Bases , Método Doble Ciego , Femenino , VIH-1/aislamiento & purificación , Humanos , Masculino , Placebos , ARN Catalítico/uso terapéutico , Carga ViralRESUMEN
Fosamprenavir, the prodrug formulation of amprenavir, is a protease inhibitor recently approved in the US for the treatment of HIV infection. This agent combines the pharmacological profile of amprenavir with a low pill burden and flexible dosing schedule. Three large international trials have been completed. In treatment-naive patients, fosamprenavir, both ritonavir-boosted and -unboosted, met primary end points of non-inferiority against nelfinavir. Among naive patients, no protease inhibitor mutations emerged in those failing the boosted fosamprenavir regimen. Boosted fosamprenavir was compared to lopinavir/ritonavir in treatment-experienced patients. Non-inferiority was not achieved but similar numbers of patients achieved viral suppression when fosamprenavir was dosed twice-daily. Fosamprenavir demonstrates a favourable lipid profile in naive patients, and a low incidence of adverse effects. Fosamprenavir, as with lopinavir/ritonavir, distinguishes itself among other protease inhibitors with its potent activity in those with advanced HIV. Future trials comparing fosamprenavir with current standard regimens will further assist in defining its role in clinical practice.