title: Photopheresis in HIV-1 infected patients utilizing benzoporphyrin derivative (BPD) verteporfin and light.
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.
authors.affiliation: RPCI, Buffalo, NY 14263, USA. zale.bernstein@roswellpark.org
authors.forename: Zale P
authors.initials: ZP
authors.lastname: Bernstein
authors.forename: Thomas
authors.initials: T
authors.lastname: Dougherty
authors.forename: Sandra
authors.initials: S
authors.lastname: Gollnick
authors.forename: Stanley A
authors.initials: SA
authors.lastname: Schwartz
authors.forename: Supriya D
authors.initials: SD
authors.lastname: Mahajan
authors.forename: James
authors.initials: J
authors.lastname: Kepner
authors.forename: Adam
authors.initials: A
authors.lastname: Sumlin
authors.forename: Carleton
authors.initials: C
authors.lastname: Stewart
authors.forename: Paul
authors.initials: P
authors.lastname: Wallace
authors.forename: Adaffaras
authors.initials: A
authors.lastname: Adal
authors.forename: Harold
authors.initials: H
authors.lastname: Walder
authors.forename: Bernard
authors.initials: B
authors.lastname: Poiesz
mesh_terms: D019380:Anti-HIV Agents / Q000009:adverse effects / Q000494:pharmacology*; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002470:Cell Survival; D015658:HIV Infections / Q000188:drug therapy / Q000628:therapy*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D007962:Leukocytes / Q000821:virology; D008027:Light; D018655:Lymphocyte Count; D017893:Photopheresis / Q000009:adverse effects / Q000379:methods*; D011166:Porphyrins / Q000009:adverse effects / Q000494:pharmacology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D000077362:Verteporfin; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D011166:Porphyrins; D000077362:Verteporfin