The emergence of human immunodeficiency virus type 1 (HIV-1) variants with different sensitivities to serum neutralization and biologic phenotype was studied for 2-5 years after primary HIV-1 infection in 5 subjects. In 3 subjects, the initial virus isolate from seroconversion could be neutralized by autologous serum, but isolates obtained at two subsequent times exhibited reduced sensitivity to serum neutralization, decreased replication in primary macrophages, and increased ability to induce syncytia. Two of these 3 subjects progressed to AIDS and died. Sequential virus isolates from the other 2 subjects showed variability in sensitivity to serum neutralization or biologic features. These patients remained relatively stable in clinical status. Thus, viruses isolated at seroconversion appear to be either non-syncytium-inducing, strong macrophage-tropic, serum neutralization-sensitive phenotypes with stable clinical status or to have escaped neutralization by autologous sera over time, have reduced macrophage tropism and increased syncytia formation, and be associated with disease progression.

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Summary The objective of this study was to assess the ability of HIV‐1 to establish an in vitro infection of primary human umbilical vein endothelial cells (HUVEC). The HUVEC and colon carcinoma cell lines were inoculated with different isolates of HIV‐1 (HIV‐1SF2, HIV‐1McK and HIV‐1LAI) and productive viral infection was assessed by both the detection of p24 core antigen in the culture supernatants and the presence of specific spliced HIV mRNA. The infection which was detected in the inoculated HUVEC and all the colon carcinoma cell lines could not be blocked using an antibody targeted against the CD4 receptor. Furthermore, the HIV‐inoculated HUVEC secreted elevated levels of IL‐6 and this increase was found to be proportional to the size of the viral inoculum. No changes in the production of IL‐lβ, TNF‐α, IFN‐α and IFN‐γ were detected following HIV infection. The colon carcinoma cells, however, did not secrete increased levels of these cytokines following HIV‐1 inoculation. These results confirm that non‐CD4 expressing cells, such as endothelial cells and certain colon epithelial cells, serve as targets and reservoirs for HIV. Moreover, the production of IL‐6 by HIV‐infected endothelial cells may be a contributing factor to the aberrant immunoregulation associated with HIV infection in vivo.