concerning the option of continuing pregnancy. 
5.4 Further Immune Suppression Precipitated by the Release of Active Infectious 
HIV-1 Virus From CTL-Lysed HIV-Infected Macrophages 
5.4. 1 The magnitude of this risk is uncertain, however, most intracellular HIV- 1 is not 
infectious and becomes infectious only after budding from infected cell membranes. 
5.4.2 Clinical and laboratory parameters will be monitored for evidence of exacerbation of 
disease. See study schedule, Section 11. 
5.4.3 CD4 + T-cells will be monitored in samples taken prior to each injection and at each visit 
thereafter. Viral burden will also be monitored (see Study Schedule, Section 1 1.0). 
5.5 Exacerbation of Disease Due to the Killing of Uninfected CD4 T-Cells as a 
Result of HIV-1 IIIB ENV Toxicity 
The magnitude of this risk is uncertain, however, previous vaccine studies, using HIV- 1 ENV 
soluble antigen have not caused any measurable side effects in treated subjects 19 Moreover, 
no indications of significant CD4 + T cell instability or other safety related symptoms have 
occurred in four HIV-1 positive subjects who received a series of three injections of HIV-IT 
(V)-transduced autologous fibroblasts and have been followed for intervals of from two 
weeks to two months beyond the third injection. 
6.0 Risk Management 
6. 1 The risks to subjects and health care professionals from the blood drawing will be minimized 
by careful attention to technique and close subject follow-up. The theoretical risks associated 
with gene therapy will be minimized by manufacturing practices and procedures and quality 
control testing. 
6.2 Safety will be evaluated by physical examination, interim clinical history, and laboratory 
analyses. Any deviations from normal will be scored according to the ACTG toxicity scale 
included in Section 12.0. 
6.3 Adverse reactions associated with product administration will be treated symptomatically by 
the principal investigators. If any subjects experience adverse reactions which are 
incapacitating or life threatening, the appropriate interventional therapy will be promptly 
administered. If recurrent grade 3 or greater ACTG toxicity, possibly or probably related to 
study therapy, is encountered in a subject, further administration of HIV-IT (V) will be 
suspended in that subject. If repeated grade 3 or greater toxicity, possibly or probably related 
to study therapy, is encountered in multiple subjects, modifications in this study will be 
implemented as set forth in Section 6.5 below. 
6.4 The Investigators will furnish the Sponsor with Safety Reports after subjects have completed 
their visit 2 weeks after the third injection, at 6 months and after their 1, 2 and 3 year follow- 
up visits. If subjects develop symptoms which justify further diagnostic tests and/or 
procedures, results of such tests and/or procedures should be reported in appropriate Case 
Report Forms. Such Case Report Forms will be submitted to Viagene with the Safety 
Reports even if test results are still pending. Any follow-up test/procedure information 
should be forwarded to Viagene as soon as results are available. 
6.5 Impact of Adverse Reactions on Study Plan: Dosage Modification Schedule 
6.5.1 If recurrent grade 3 or greater ACTG toxicity, possibly or probably related to study 
therapy, (see Section 12.0) is observed in four subjects receiving 10 7 cfu of HIV-IT 
(V), the remainder of the subjects will receive a lower dose of 10 6 cfu. If recurrent 
grade 3 or greater ACTG toxicity, possibly or probably related to study therapy, is 
observed in three subjects receiving the lower dose, this study will be suspended. 
19 Redfield R.R. et al„ N. E. Journal of Med., 324:1677-1684 (1991). 
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