Immune control of HIV-1 infection after therapy interruption: immediate versus deferred antiretroviral therapy

Paola Paci,Filippo Castiglione,Massimo Bernaschi,Gianpiero D'Offizi,Rossella Carello

doi:10.1186/1471-2334-9-172

Abstract

BackgroundThe optimal stage for initiating antiretroviral therapies in HIV-1 bearing patients is still a matter of debate.MethodsWe present computer simulations of HIV-1 infection aimed at identifying the pro et contra of immediate as compared to deferred Highly Active Antiretroviral Therapy (HAART).ResultsOur simulations highlight that a prompt specific CD8+ cytotoxic T lymphocytes response is detected when therapy is delayed. Compared to very early initiation of HAART, in deferred treated patients CD8+ T cells manage to mediate the decline of viremia in a shorter time and, at interruption of therapy, the virus experiences a stronger immune pressure. We also observe, however, that the immunological effects of the therapy fade with time in both therapeutic regimens. Thus, within one year from discontinuation, viral burden recovers to the value at which it would level off in the absence of therapy.In summary, simulations show that immediate therapy does not prolong the disease-free period and does not confer a survival benefit when compared to treatment started during the chronic infection phase.ConclusionOur conclusion is that, since there is no therapy to date that guarantees life-long protection, deferral of therapy should be preferred in order to minimize the risk of adverse effects, the occurrence of drug resistances and the costs of treatment.

Highlights

The optimal stage for initiating antiretroviral therapies in Human Immunodeficiency Virus (HIV)-1 bearing patients is still a matter of debate
Possible drawbacks to very early initiation of Higly Active Antiretroviral Therapy (HAART), include prolonged exposure to antiretroviral therapy without known clinical benefit, exposure which could result in drug toxicities and development of antiretroviral drug resistance, the need for continuous therapy with strict adherence and associated adverse effect on quality of life and, last but not least, increased costs [5]
Given there is no therapy to date that guarantees lifelong protection, deferral of therapy should be preferred in order to minimize the risk of adverse effects, the occurrence of drug resistances and the costs of treatment

Summary

Introduction

The optimal stage for initiating antiretroviral therapies in HIV-1 bearing patients is still a matter of debate. Antiretroviral therapy has significantly modified the approach to treatment of the Human Immunodeficiency Virus (HIV) infection. Positive effects of Higly Active Antiretroviral Therapy (HAART) include suppression of plasma viremia below detection level, rising circulating CD4+ T cell count, reduction of the incidence of acquired immunodeficiency syndrome (AIDS) and of death [1,2,3]. It is still unclear, what the "ideal moment" is for initiating HAART. The demand of new therapeutic strategies and the urgent need to shed light on the issue of when is the best time for initiating therapy together with the high cost and long follow-up required by in vivo testing, provide solid arguments for the use of computational models as predictive tools

Methods

Results

Discussion

Conclusion