unprecedented progress in understanding the causative agent at the molecular level, and 
in palliating the myriad complications of AIDS, HIV disease remains refractory to 
treatment. In 1993, death within a few years is a virtual certainty for patients with 
CDC-defined AIDS. Epidemiological considerations are also compelling: WHO projects 
that about 40 million people will have HIV infection worldwide by the year 2000 (3). 
More inclusive projections that take account of under-reporting suggest that the world 
at the turn of the century may harbor as many as 100 million people infected with HIV 
(4,5). Current WHO estimates for cumulative HIV infections since the start of the 
pandemic total over thirteen million and include the following subtotals: over 1.5 
million in North America and Europe, 1.5 million in Latin America and the Caribbean, 
more than 8 million in sub-Saharan Africa, 75,000 in North Africa and the Middle East, 
and over 1.5 million in South and Southeast Asia (3,4). 
More than 2 million of the world's HIV-infected people have developed AIDS; most of 
them have died (3). The social fabric of the African continent has been severely 
threatened by this disease-in some African cities, 30% adult infection rates are 
estimated and up to 80% of hospital beds are occupied by patients with AIDS (3,4). The 
explosive spread of HIV now being observed in South and Southeast Asia, the new 
epicenter, portends social calamity in those regions also. In addition to the horrific 
individual suffering, the world-wide economic losses stemming from this disease that 
strikes primarily in the most economically productive age groups are colossal and 
growing (4). 
B. Rationale for Ribozvme Gene Therapy & Previous Data with the HIV-1 Leader 
Sequence Ribozvme . While the clear gravity of the pandemic compels consideration of 
innovative approache as well as streamlined Phasel and 2 testing, it cannot of course 
alone justify experimental human trials. Why move ahead now with gene therapy in 
particular for HIV infection? At root, the HIV problem is a genetic one: infection with 
this retrovirus results in reverse transcription of the viral RNA and permanent 
integration of the resulting DNA into the genome of the infected cell (6). There the 
provirus becomes an inheritable feature of the cell and retains the potential for viral 
expression and production of progeny virus for the duration of the cell’s lifetime. 
Patients with HIV-1 infection have become in effect, genetically mosaic for HIV. In this 
sense, AIDS is a genetic disease, albeit an acquired one. 
Recombinant DNA Research, Volume 18 
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