antiretroviral drug to be approved by the FDA for AIDS, and has been shown 
in a randomized, placebo-controlled trial to prolong the lives of most AIDS 
patients who take it (7). In addition, two recent studies (8,9) have shown that 
zidovudine can delay progression of HIV disease in patients with CD4+ 
counts below 500 cells/mm3. Current recommendations are that patients with 
HIV infection and CD4+ counts below 500 cells/mm be treated with 
zidovudine under close medical supervision (10,11). Dideoxyinosine (ddl), 
another nucleoside analogue inhibitor of reverse transcriptase, has recently 
been approved by the FDA for treatment of HIV infection in individuals 
intolerant to or failing therapy with zidovudine (12). Dideoxycytidine (ddC) is 
a related nucleoside analogue that has also been licensed for use in 
combination with zidovudine. 
There are, however, some significant practical and theoretical 
difficulties with available antiretroviral agents. Although mortality and 
frequency of opportunistic infections are reduced in patients taking 
zidovudine, a complete and sustained improvement in immune status has not 
been achieved (13,14). In addition, frequent toxic effects prevent many 
individuals from tolerating these drugs for extended periods (15). Recent in 
vitro evidence of retroviral resistance has also been presented, although the 
clinical importance of this is as yet unknown (16). In hopes of increasing 
efficacy and reducing toxicity, studies are now underway examining the 
potential role of combination therapies for HIV infection. Such approaches 
include combined therapy with two or more agents from the same class (e.g., 
reverse transcriptase inhibitors) or from distinct classes with different 
mechanisms of action (e.g., RT inhibitors plus immunomodulators). Despite 
the major advances in treating HIV disease that have occurred in the past five 
years, it is clear that the need is still great for more efficacious, less toxic 
therapies with novel mechanisms of action. 
2.2 Bone Marrow Transplantation and Lymphocyte Transfers in AIDS 
The combination of antiretroviral therapy and immune reconstitution is 
an attractive approach to treating HIV infection. Transplantation of 
hematopoietic elements has been shown to correct the immune defects in 
certain primary immune deficiency diseases including severe combined 
immune deficiency, where both T- and B-cell functions are either absent or 
markedly impaired (17-19). Immunologic reconstitution has been attempted 
in AIDS patients using biologic-response modifiers, syngeneic and 
allogeneic bone marrow transplantation, and peripheral leukocyte infusions 
(20-27). We have previously reported a patient with AIDS treated with a 
combination of syngeneic bone marrow transplantation and peripheral 
lymphocyte transfers using the patient's uninfected identical twin as donor 
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Recombinant DNA Research, Volume 16 
