Cytotoxic T-lymphocyte induction in asymptomatic HIV-1-infected patients immunized with Retrovector-transduced autologous fibroblasts expressing HIV-1IIIB Env/Rev proteins.

OBJECTIVE: To demonstrate the safety and enhancement of HIV-1-specific immune responses in HIV-infected asymptomatic patients following treatment with retroviral vector (Retrovector)-transduced autologous fibroblasts (VTAF) expressing HIV-1IIIB Env/Rev proteins. DESIGN: A non-placebo-controlled, single arm Phase I study. PARTICIPANTS: Four HIV-1-seropositive asymptomatic volunteers were selected based on age (18-50 years), CD4/CD3 lymphocyte counts (> 600 x 10(6)/l or > 40%), and positive delayed-type hypersensitivity test to at least one recall antigen. INTERVENTIONS: Patients were treated at 2-week intervals with a total of three intramuscular injections of irradiated autologous fibroblasts transduced with a molecularly engineered, non-replicating amphotropic murine retrovector encoding the HIV-1IIIB Env/Rev proteins. MAIN OUTCOME MEASURES: The clinical status of patients was assessed by history, physical examination, serum chemistry and hematology, CD4/CD3 lymphocyte counts, HIV viral burden, and monitored throughout the study to detect potentially treatment-induced toxic or unwanted side-effects. In addition, HIV-1-specific cytotoxic T-lymphocyte (CTL) activity was measured to determine the biological activity of VTAF. RESULTS: No acute local or systemic adverse events occurred following three injections with VTAF. Furthermore, a statistically significant increase of CD8+ CTL activity against HIV-1IIIB Env/Rev-expressing targets was observed in peripheral blood mononuclear cells from two out of four patients. CONCLUSIONS: This is the first report of the administration of a gene transfer treatment to HIV-1-infected patients and provides initial support for the safety and activity of retrovector-transduced fibroblasts administered to asymptomatic patients. This treatment resulted in the detection of increased HIV-1IIIB Env/Rev-specific CTL activity in two HIV-seropositive patients and could provide a better understanding of the role of CTL activity in HIV disease progression.

Tc-99m methylene diphosphonate versus Tc-99m pyrophosphate: biologic and clinical comparison.

The biologic and imaging characteristics of Tc-99m MDP and Tc-99m PPi were compared in animals and patients using freeze-dried bone-imaging kits. Biodistribution data in rabbits showed Tc-99m MDP had slightly higher bone uptake, significantly lower blood levels, and faster urinary excretion compared with Tc-99m PPi. Duplicate studies performed on ten patients showed the following: (a) blood clearance of Tc-99m MDP was more prompt and complete, resulting in significantly lower blood levels at 4 hr; (b) urinary excretion was greater with Tc-99m MDP than with Tc-99m PPi; and (c) Tc-99m PPi showed significant red-cell labeling, whereas Tc-99m MDP did not. Image quality was generally better with Tc-99m MDP than with Tc-99 m PPi, although there was no obvious difference in diagnostic sensitivity between the two agents.