Abstract
The requirements for the eradication of HIV in infected individuals are unknown. Intermittent administration of the immune activator interleukin‐2 (IL‐2) in combination with highly‐active antiretroviral therapy (HAART) has been suggested as an effective strategy to realize long‐term control of HIV replication in vivo. However, potential latent virus reservoirs are considered to be a major impediment in achieving this goal. In this paper, a new mathematical model is designed and used to monitor the interactions between HIV, CD4+ T‐cells, CD8+ T‐cells, productively infected and latently infected CD4+ T‐cells, and to evaluate therapeutic strategies during the first 3 years of HIV infection. The model shows that current anti‐HIV therapies, including intermittent IL‐2 and HAART, are insufficient in achieving eradication of HIV. However, it suggests that the HIV eradication may indeed be theoretically feasible if such therapy is administered continuously (without interruption) under some specified conditions. These conditions may realistically be achieved using an agent (such as a putative anti‐HIV vaccine) that brings about a concomitant increase in the proliferation of HIVspecific CD4+ T‐ and CD8+ T‐cells and the differentiation of CD8+ T‐cells into anti‐HIV cytotoxic T lymphocytes (CTLs).
Highlights
“Hit early and hard” is a well-known strategy for the treatment of HIV infection often involving highly-active anti-retroviral therapy (HAART)
Since the administration of IL-2 during intermittent HARRT has been used to reactivate latent CD4 þ T cell viral reservoirs, this study focuses on investigating the effects of intermittent IL-2 plus highly-active antiretroviral therapy (HAART)
In addition to enhancing b and p, the use of an antiHIV vaccine relaxes the requirement for HIV eradication in terms of p. These results imply that a putative anti-HIV vaccine, which is capable of increasing the proliferation of HIV-specific CD4 þ T and CD8 þ Tcells by 20-fold (i.e. b 1⁄4 20 £ 4 £ 1027) and the differentiation of CD8 þ anti-HIV cytotoxic T lymphocytes (CTLs) to p $ 0:65; can eradicate HIV provided it is used in conjunction with a continuous 80% effective HAART and IL-2 therapy and another drug that can eliminate the non-CD4 þ T cell HIV reservoirs ðr3 1⁄4 0Þ: By augmenting b and p and relaxing the requirement in terms of p, the use of anti-HIV vaccine makes HIV eradication a more realistic possibility
Summary
The model shows that current anti-HIV therapies, including intermittent IL-2 and HAART, are insufficient in achieving eradication of HIV. It suggests that the HIV eradication may be theoretically feasible if such therapy is administered continuously (without interruption) under some specified conditions. These conditions may realistically be achieved using an agent (such as a putative anti-HIV vaccine) that brings about a concomitant increase in the proliferation of HIVspecific CD4 þ T- and CD8 þ T-cells and the differentiation of CD8 þ T-cells into anti-HIV cytotoxic T lymphocytes (CTLs)
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