• evaluate the effects of this therapy on HIV-1 viral load by PCR analysis [ Time Frame: 9 months ]
  
• evaluate the effects of this therapy on CD4+, CD8+ cells and CD4/CD8 ratio [ Time Frame: 9 months ]
  
• evaluate the effects of this therapy on the patient's immune system, by skin reactivity to a standard anergy panel [ Time Frame: 9 months ]
  
• The objectives of this clinical trial are to: assess the safety of using extracorporeal photoimmune therapy with the photosensitizing agent UVADEX in the treatment of HIV-1 infection. [ Time Frame: 9 months ]
  

Rationale for the Use of ECP with UVADEX in Patients with HIV-1 Infection

Studies have demonstrated that psoralen and ultraviolet A light inactivate HIV virus in vitro. Edelson, et al, showed that extracorporeal photochemotherapy (ECP) with psoralen primarily targets the CD4+ cell, the population predominately affected by HIV-1 infection. It is postulated that the re-infusion of the ECP treated cell fraction, free virus, cell-associated virus along with whole cells, cell fragments, and soluble antigens, may serve to engender a specific HIV immune response.

A twenty-patient study using ECP with psoralen was conducted by Bisaccia, et al. In this study, patients were HIV positive by enzyme linked immunosorbent assay and these positive results were confirmed by Western blot test. Patients were staged as Walter Reed class WR3 to WR5. Extracorporeal photoimmune therapy was administered on two consecutive days on a monthly basis for 6-29 months. This study reported that CD4 counts declined more slowly than historical controls. Walter Reed classification improved in 55% (11/20), was stable in 35% (7/20) and declined in 10% (2/20) of the patients treated in this study.

One measure in the "in vivo" evaluation of T-cell function is provided by skin reactivity to recall antigens (DTH). A lack of this response has been associated with progression of HIV disease. In the Bisaccia study, skin reactivity to recall antigens (DTH) improved in 55% (11/20) patients, were stable in 35% (7/20), progressed to anergy in 5% (1/20). One patient was initially anergic and remained anergic post-treatment. Following treatment with ECP, 60% (9/15), displayed normal skin test responses, whereas the baseline examinations had been normal in only 5% (1/19). In addition, 21% (4/19) of patients showed a partial skin test response. Only 10% (2/20) of patients developed a new opportunistic infection. This included the patient initially anergic and who remained anergic and the patient who progressed to anergy post-ECP treatment.

DESCRIPTION OF THE UVAR® XTSÔ PHOTOPHERESIS SYSTEM

Photopheresis (or extracorporeal photoimmune therapy [ECP]) is a process developed by THERAKOS, Inc., a Johnson and Johnson Company. During the process of ECP, whole blood is drawn from the patient over several cycles, centrifuged and separated into the components of plasma, white cells (or buffy coat), and red blood cells. A portion of the white cells and the plasma are saved in a separate compartment. The remaining plasma and red blood cells are immediately returned to the patient.

The saved buffy coat (white blood cells) and plasma are inoculated with the photosensitizing agent UVADEX. Photoactivation begins when the suspension is exposed to a prescribed amount of ultraviolet-A light. After photoactivation is complete, the treated suspension is returned to the patient.

Photopheresis performed using the UVAR XTS is a continuous process. During the entire therapy, the patient remains connected to the photopheresis instrument. The duration of time between completion of the buffy coat collection and reinfusion of the light-activated buffy coat is approximately 30 minutes.