PubMed · 8451629
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D E Koshland. 1993-03-05. Basic research (III): Priorities.. https://doi.org/10.1126/science.8451629
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Sequences of the HIV-2 envelope C2-C3 region were obtained after direct PCR amplification of proviral DNA from the brain and peripheral blood mononuclear cells of an HIV-2-infected AIDS patient. Tissue-specific sequences confirmed previous observations that HIV-2 is indeed present in the central nervous system of infected individuals. Distinct but related quasi-species were present in these two different tissues of the same individual. Residues at position 18 and 19 of the V3 loop and overall charge of the loop suggest that the brain virus was NSI/macrophage tropic; whereas the sequences from the two blood samples were indicative of a SI/T-cell tropic virus. This is the first description of these two genotypes in the same HIV-2-infected individual. Analysis of more samples from different compartments would help to better understand tissue-specific factors in quasi-species evolution in vivo.
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Macrophages play an important role in the immunopathogenesis of AIDS. The objective of this study was to investigate the possibility of specific targeting of antivirals such as azidothymidine (AZT) to macrophages, using nanoparticles as a colloidal drug carrier. The body distribution of AZT bound to nanoparticles and as a control solution was studied in rats after intravenous and peroral administration. 14C-Labeled AZT was bound to nanoparticles in the presence of bis(2-ethylhexyl)sulfosuccinate sodium. The radioactivity was measured in different organs including those containing large numbers of macrophages. After intravenous injection, the concentrations of AZT were up to 18 times higher in organs belonging to the reticuloendothelial system (RES) when the drug was bound to nanoparticles than after injection of an aqueous AZT solution. Likewise, after oral administration the nanoparticle formulation delivered AZT more efficiently to the RES than the aqueous solution. In addition, the blood concentration was significantly higher after oral administration of nanoparticles. These results demonstrate that nanoparticles are a promising drug-targeting system for AZT to the RES organs. The increase in drug availability at the sites containing abundant macrophages may allow a reduction in dosage to avoid systemic toxicity.