Recombinant DNA Advisory Committee - 12/2-3/93 
of the Clinton Administration. 
In conclusion, most RAC members agreed with Dr. Ellis' suggestion that the RAC 
should draft a letter outlining the specific recommendations to the OPRR for 
consideration and distribution to local IRBs as well as proposed amendments to the 
Points to Consider. The working group should develop language that addresses the 
following: (1) recommendations for contraception by males/females, (2) responsibility 
for financial costs of the experiment, (3) the necessity for long-term follow-up, (4) 
request for autopsy, and (5) protection of patient confidentiality when information is 
released to the media. 
XIII. ADDITION TO APPENDIX D OF THE NIH GUIDELINES REGARDING A HUMAN 
GENE TRANSFER PROTOCOL ENTITLED: AN OPEN LABEL, PHASE I/II 
CLINICAL TRIAL TO EVALUATE THE SAFETY AND BIOLOGICAL ACTIVITY OF 
HJV-IT(V) (HIV-1 IIBenv/RETROVIRAL VECTOR) IN HIV- 1 INFECTED 
SUBJECTS/DR. HAUBRICH 
Review-Dr. Straus 
Dr. Walters called on Dr. Straus to present his primary review of the protocol submitted 
by Dr. Richard Haubrich of the University of California at San Diego Treatment Center, 
San Diego, California. The primary objectives of this protocol are to evaluate safety and 
to ascertain the immunological effects of the human immunodeficiency virus (HTV)- 
IT(V) vector in HIV-1(+) asymptomatic individuals. The treatment is designed to 
stimulate a CTL response against the HIV-1 env/rev proteins. This response could lead 
to a reduction in the number or elimination of HIV-infected cells. Enhanced viral 
clearance could reverse immunosuppression or inhibit its progression. This proposal 
represents an extension of Dr. Galpin's previously approved protocol in which a murine 
retroviral vector containing HIV-1 rev and env genes was injected intramuscularly into 
HIV( + ) subjects. This current proposal incorporates the following modifications as 
compared to Dr. Galpin's protocol: (1) patient eligibility will be expanded to include 
patients with CD4 counts between 200 and 499, (2) the highest virus inoculum proposed 
for this study is 10 7 efu, (3) doses will be administered to multiple muscle sites, (4) doses 
will be administered at 3 monthly intervals rather than biweekly intervals, and (5) 
antiviral therapy will be permitted but withheld for 3 days prior to and 3 days following 
vector injection. The vector, study rationale, and the preclinical data are well presented. 
The Informed Consent document is acceptable with the inclusion of modifications 
relating to request for autopsy and long-term follow-up. There are still several 
outstanding issues that should be addressed by the investigators. The current proposal is 
an extension of a previous study from which data is not yet available. The investigators 
should verify that the previous doses, including the 10 7 efu proposed for this study, have 
been well tolerated. The investigators should explain the rationale for proposing 
multiple injection sites, i.e., was a single injection site inadequate to confer a maximal 
response? Even though no interpretable data has been reported for the Phase I study, 
the investigators are requesting expansion to a Phase II trial. Although the vector may 
be safe, the RAC should carefully consider accelerated transition through these phases. 
Recombinant DNA Research, Volume 18 
[541] 
