Human immunodeficiency virus type 1 (HIV-1) isolates from perinatally infected infants and children were examined for syncytium-inducing (SI) capacity. All isolates from 14 infants < 1 year old had non-syncytium-inducing (NSI) HIV-1 phenotypes. Within their first year, 10 infants progressed to AIDS and 3 died. Of isolates from 26 children > 2 years old, 13 had SI HIV-1 phenotypes and 13 had NSI strains. Children with SI virus had significantly lower CD4+ cell counts standardized for age and were significantly older than those with NSI strains (P = .008 and .001, respectively); the effect of viral phenotype on CD4+ lymphocytes could not be detected independent of age. In another group, children with SI strains were more likely to show in vitro zidovudine resistance. Results suggest a biphasic response to HIV infection in children. Progression to AIDS may occur rapidly in infants with NSI HIV-1, but older children tend to have SI phenotypes and lower CD4+ lymphocyte counts and more often show zidovudine resistance.
A recombinant virus vector constructed from adeno-associated virus (AAV) that has been altered to carry the human alpha1-antitrypsin (hAAT) gene expressed from a hybrid chicken beta-actin promoter with a cytomegalovirus enhancer has been developed. The construct has been shown to initiate the production of hAAT in animal models closely matching the proposed human trial. The proposed clinical trial is an open-label, phase I study administering recombinant adeno-associated virus alpha1-antitrypsin (rAAV2-CB-hAAT) gene vector intramuscularly to AAT-deficient human subjects where gene expression can be measured directly in blood samples to assess safety. Safety parameters will be measurement of changes in serum chemistries and hematology, urinalysis, pulmonary function testing, semen assay for vector genomes, immunologic response to AAT, and AAV, as well as reported subject history of any symptoms.
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