Development Of Viral Resistance Research Articles

Challenges in the therapy of HIV infection

Drags that inhibit human immunodeficiency virus (HIV) replication have been shown to have clinical utility in patients with HIV infection. However, the immunological improvement inauced by available anti-HIV therapies in patients with acquired immune deficiency syndrome (AIDS) is incomplete and transient. Explanations for this may include immunological barriers to complete reconstitution, low therapeutic indices of the available drugs, and the development of viral resistance. An understanding of these processes, as discussed here by Robert Yarchoan and colleagues, may provide important leads for the development of improved therapy for AIDS.

Development of resistance to zidovudine in HIV strains isolated from CD4+ lymphocytes and plasma during therapy

An assay based on production of HIV antigen in cultures of CD4+ lymphocytes infected ‘in vitro’ with cell-free virus was established. Using this assay it was possible to isolate, propagate and reliably determine the zidovudine susceptibility of HIV isolates from all patients despite differences in cellular tropism and syncytium inducing capacity. Using this assay, differences in zidovudine susceptibility of 52 serial isolates obtained from 16 patients before and after initiation of therapy were examined. HIV with a 10- to 100-fold reduced susceptibility to zidovudine were isolated from 13 patients as early as 4 months after initiation of therapy. Number of months of zidovudine treatment was strongly associated with development of viral resistance, and high CD4 cell counts tended to be associated with lower rates of development of resistance. That patients can harbor mixtures of virus strains with different susceptibility to zidovudine was confirmed by the differences in susceptibility between isolates obtained simultaneously from CD4+ lymphocyte and plasma, and by the differences in susceptibility between virus strains isolated from clones of CD4+ lymphocytes.