Search PubMed⌕ Search

Biomedical subjects

W A Carter

Publications and source records attributed to W A Carter.

128 records · Page 8Linked to original sources

Clinical studies with mismatched double-stranded RNA.

Mismatched inducer/activator therapy has demonstrated areas of definite clinical promise in its initial human trials. Indeed, the mismatched dsRNA may even prove more efficacious than conventional (exogenous) interferon therapy for several reasons including: (a) First, the potential for generating multiple species of interferons, thereby removing the possible necessity of targeting a specific type (or subtype) of interferon to a particular cell type, (b) Secondly, the known ability of the mismatched inducer to activate the intracellular mediators which are synthesized after cellular exposure to the various types of interferon, (c) Lastly, the recently demonstrated ability of the inducer/activator in combination with interferon to override acquired cellular resistance to interferon alone (13).

Adult↗

Synergistic inhibition of AZT-resistant HIV by AZT combined with poly(I):poly(C12U), without synergistic toxicity to bone marrow progenitor cell elements.

Mutation of human immunodeficiency virus (HIV) to drug resistance is an obstacle to HIV containment, and may account for the transitory nature of the improvement in CD4 cell counts of patients receiving azidothymidine (AZT). The emergence of AZT-resistant (AZTR) virus might be suppressed if a second therapeutic could be added; however, such a regimen would have to confer not only additional control over HIV replication but also no additional toxicity, especially to bone marrow progenitor cells. In the present study, HIV was isolated from patients receiving AZT alone and was studied for sensitivity to the mismatched double-stranded RNA, poly(I):poly(C12U) (ampligen). In addition, the combination of poly(I):poly(C12U) plus AZT was studied in vitro for toxicity to bone marrow CFU-GM and in patients receiving combined therapy for bone marrow toxicity. HIV isolated from patients receiving AZT alone showed higher resistance to AZT than wildtype virus, but remained sensitive to poly(I):poly(C12U). Poly(I):poly(C12U) and AZT were synergistic in inhibiting all isolates of HIV tested, regardless of their AZTR phenotype. Furthermore, the combination of poly(I):poly(C12U) and AZT showed no toxicity in vitro to bone marrow CFU-GM compared to AZT alone. In 11 HIV infected individuals receiving the combinational regimen, bone marrow function gradually improved. These results indicate that poly(I):poly(C12U) was active against AZTR HIV, synergistic with AZT and did not convey added toxicity.

Antiviral Agents↗