Photopheresis in HIV-1 Infected Patients Utilizing Benzoporphyrin Derivative (BPD) Verteporfin and Light

Zale   P.   Bernstein; Thomas      Dougherty; Sandra      Gollnick; Stanley   A.   Schwartz; Supriya   D.   Mahajan; James      Kepner; Adam      Sumlin; Carleton      Stewart; Paul      Wallace; Adaffaras      Adal; Harold      Walder; Bernard      Poiesz

doi:10.2174/157016208783885001

Abstract

An ex vivo trial utilizing photopheresis with Benzoporphyrin Derivative as the photoactive compound, identified the minimum energy levels of light and concentrations of BPD that eradicated both cell-free and cell-associated HIV- 1 infectivity without destroying the virus particles or infected leukocytes. Leukocytes remained viable with altered chemokine/cytokine expression. Apoptosis was induced in a minority of CD4 but not CD8 positive cells with a statistically significant increase in cytolytic T-cell activity. In the 24 week clinical trial in 7 HIV-1 infected patients, three who had rapidly rising viral loads prior to initiating therapy stabilized. Two had a sustained greater than 0.5 log decrement and 5 had stable plasma viral loads (less than a 0.5 log increment or decrement) with varied effects on absolute CD4 and CD8 positive lymphocytes counts. One achieved a greater than 1 log decrement in HIV-1 plasma viral load and undetectable in vivo cell-free and cell-associated HIV-1 infectivity with an increased in vitro lymphocyte mitogen stimulation index. Under amended protocol, 5 additional 12 month courses were administered to three additional patients and two of the previous enrollees. Area under the curve for viral load showed a significant decrease from pre- to post-therapy (p 0.007). No associated toxicities were observed.

Keywords: HIV, photopheresis, benzoporphyrin, granzyme, chemokine

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