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

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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