Recombinant DNA Advisory Committee - 09/14-15/92 
Dr. Dronamraju asked the investigators for an estimation of the number of patients 
available for the various stages of diseases. Dr. Lane explained that with regard to 
staging of infection, staging procedures were developed before extensive knowledge of 
HIV, the role of CD4( + ) cells, and techniques for tagging the disease by examining 
CD4( + ) counts were understood. Rather than approaching HIV research by examining 
discreet stages, it is more efficacious to gather data for future interpretation regarding 
disease stage. 
Dr. Parkman asked if there is a minimum level of transduction that will be informative. 
If a large number of patients exhibit transduction levels that are less than informative, 
will they be excluded from participating in the protocol? Dr. Blaese explained that 
although transduction levels have proven to be variable, they have always been able to 
transduce at a minimum level of 0.5%. Therefore, all patients would be eligible since 
there has never been a clinical population that was not transducible at this level. The 
level of marking will be carefully evaluated. Patients entering this protocol will receive 
approximately 20-fold more lymphocytes than patients receive in the adenosine 
deaminase (ADA) protocol. Transduced cells have been detected in the ADA gene 
therapy patients as soon as one day following infusion. There should be detectible levels 
of transduced cells based on the ADA protocol data. Dr. Parkman explained that there 
is a basic biological difference between the ADA and HIV protocols. Presumably in the 
ADA protocol, introduction of the neomycin resistance (neo R ) gene confers a selective 
advantage. Dr. Parkman stated that in HIV( + ) patients, the majority of cells are not 
infected with HIV. Therefore, these cells are not any different from the normal 
noninfected cells within patients. Is there a minimum level that would be valid? Dr. 
Blaese responded that although there probably is a minimum value, there is no capacity 
to assay transduction levels in a timely fashion prior to infusion. 
Ms. Buc reiterated the concerns raised by Dr. Zallen regarding the donor informed 
consent document and assessing the HIV status of the donor twin. Although the 
investigators have communicated the process by which the donor and recipient are 
solicited and counselled prior to obtaining their informed consent, the entire process 
should be included as part of the informed consent document. The current informed 
consent document does not accurately reflect the process as it currently exists. In 
addition, the section in the informed consent document that describes the 
lymphopheresis procedure should be inserted prior to the explanation of travel. The 
lymphopheresis is a major procedure, and its importance and description should not be 
understated. With regard to HIV testing of the donor, Dr. Lane explained that both the 
donor and recipient twin will have consulted a referring physician and the donor will 
have had a recent HIV test prior to coming to the NIH. In addition, NIH will retest for 
HIV infection of the donor if the RAC recommends repeat testing. 
Dr. Parkman referred to a sentence in the informed consent document stating that the 
Recombinant DNA Research, Volume 16 
[227] 
