Study Design This is a pilot study to determine the safety and feasibility of lentivirus-transduced T cell immunotherapy in patients who have failed highly active anti-retrovirus therapy (HAART) as defined by HIV levels or by intolerance to drug therapy. The lentivirus vector induces 3 forms of anti-HIV RNA: RNAi in the form of a short hairpin RNA (shRNA) targeted to an exon in HIV-1 tat/rev (shI), a decoy for HIV TAT-activated RNA (TAR), and a ribozyme that targets the host T cell CCR5 cytokine receptor (CCR5RZ). The vector is called rHIV7-shI-TAR-CCR5RZ and will be used in the transduction and expansion of autologous CD4-enriched T cells. Doses of 1 x 109 T cells will be given at 0, +6, and +12 weeks to the first cohort of 3 subjects. Following completion of this cohort, if no serious adverse events have occurred within 3 weeks of the last infusion, then the next cohort will receive 10 x 109 T cells at 0, +6, and +12 weeks using the same 8 week spacing between subjects.~Study Endpoints:~The primary endpoints of this pilot study are patient safety and study feasibility. Safety will be determined by clinical and laboratory observation and grading of adverse events, analysis of T cell repertoire clonality, and evaluation of HIV isolates for evidence of vector recombination. Feasibility will be determined by the ability to obtain suitable numbers of expanded T cells and expression of the RNA transgenes in these cells. The secondary endpoints are the duration of T cell circulation in blood post-infusion and the effect of the T cell infusion on CD4 count and on HIV load. Conventional CD4 counts and HIV RNA levels in blood will be determined at follow-up intervals.~Subject Eligibility and Number. Subjects must be HIV-1 infected adults ≥18 and ≤60 years of age who have been on HAART therapy for at least one year and have evidence of virologic failure defined by >5000 HIV RNA genome copies (gc) per mL in blood. Subjects must have a CD4 count of at least 200 CD4+ T cells/mL. This pilot study is expected to accrue five evaluable patients.
This is a pilot study to determine the safety and feasibility of lentivirus-transduced T-cell immunotherapy in patients who have failed highly active anti-retrovirus therapy (HAART).