Recombinant DNA Advisory Committee - 09/9-10/93 
Ms. Meyers indicated several concerns in her written comments about the Informed 
Consent document language. The financial responsibility of patients is not clearly stated. 
The request for autopsy includes a statement that the patient's permission for autopsy 
may not be rescinded by relatives. Mr. Capron said that he would defer to the opinion 
of the legal counsel of the University of California to determine whether this language is 
enforceable without invoking the Uniform Anatomical Gift Act. 
Dr. Carmen suggested several specific language changes in the Informed Consent 
document to convey more clearly the recombinant DNA aspects of this protocol to 
patients. Dr. Smith expressed concern about the ambiguous statements of financial risks 
to patients and the lack of request for autopsy in the Informed Consent document. He 
stated that the IRB stipulation of mandatory AZT is unnecessary. Also, there is a 
question about the possibility of generating RCR with an altered host range by 
administering a retrovirus vector to HTV infected patients. 
Regarding the issue of AZT use in acquired immunodeficiency syndrome (AIDS) 
patients, Dr. Straus said that there is a changing opinion in the medical community 
resulting from new studies. In patients with CD4 counts below 200, AZT appears to 
have beneficial effect on patient survival. But for patients with CD4 counts between 250 
and 600, which is the target patient population of this study, the current data are 
conflicting as to the beneficial effect of AZT. Dr. Straus was concerned about the 
mandatory use of AZT as suggested by the IRB. The decision to use antiviral drugs is 
best left to the primary care physicians. Dr. Post also expressed his concern about the 
requirement for AZT in healthy HIV( + ) individuals. 
Dr. Walters requested a clearer statement in the Informed Consent document as to 
whether there will be any clinical benefit to patients in this Phase I trial. Mr. Braverman 
commented on the proposed study. He expressed his reservation that the IRB has 
mandated the use of AZT for patients in this trial. He raised several points regarding 
inclusion and exclusion criteria for patients in this trial. Overall, he was pleased to see 
this gene therapy protocol reviewed by the RAC and applauded such an advancement in 
AIDS research. Dr. Nava Sarver, National Institute of Allergy and Infectious Diseases, 
NIH, expressed her support for this protocol to evaluate ribozyme treatment in HIV( + ) 
individuals. 
Investigator Response— Drs. Wong-Staal and Poeschla 
Regarding the question of RCR testing. Dr. Wong-Staal said that they are in the process 
of seeking an established laboratory to test clinical grade preparations. Preliminary 
results from her own laboratory indicate no RCR contamination. Responding to 
questions raised by Drs. Hirano and Chase regarding the detection of ribozyme 
transduced cells in the presence of untransduced cells, Dr. Wong-Staal presented data 
demonstrating that the PCR assay is capable of detecting at least one transduced cell in 
the background of 5,000 untransduced cells. Dr. Chase pointed out that the real 
question is how to analyze the differential survival rates of ribozyme transduced versus 
untransduced cells in HIV patients, and this question is not adequately addressed by this 
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Recombinant DNA Research, Volume 18 
