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Open Access Research article

Timely HAART initiation may pave the way for a better viral control

Paola Paci1*, Federico Martini2, Massimo Bernaschi3, Gianpiero D'Offizi2 and Filippo Castiglione3*

Author Affiliations

1 Biomedical University Campus, via Alvaro del Portillo 21, 00128 - Rome, Italy

2 National Institute for Infectious Diseases "Lazzaro Spallanzani", I.R.C.C.S., 00149 Rome, Italy

3 Institute for Computing Applications "Mauro Picone", National Research Council, 00185 Rome, Italy

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BMC Infectious Diseases 2011, 11:56  doi:10.1186/1471-2334-11-56

Published: 1 March 2011

Abstract

Background

When to initiate antiretroviral therapy in HIV infected patients is a diffcult clinical decision. Actually, it is still a matter of discussion whether early highly active antiretroviral therapy (HAART) during primary HIV infection may influence the dynamics of the viral rebound, in case of therapy interruption, and overall the main disease course.

Methods

In this article we use a computational model and clinical data to identify the role of HAART timing on the residual capability to control HIV rebound after treatment suspension. Analyses of clinical data from three groups of patients initiating HAART respectively before seroconversion (very early), during the acute phase (early) and in the chronic phase (late), evidence differences arising from the very early events of the viral infection.

Results

The computational model allows a fine grain assessment of the impact of HAART timing on the disease outcome, from acute to chronic HIV-1 infection. Both patients' data and computer simulations reveal that HAART timing may indeed affect the HIV control capability after treatment discontinuation. In particular, we find a median time to viral rebound that is significantly longer in very early than in late patients.

Conclusions

A timing threshold is identified, corresponding to approximately three weeks post-infection, after which the capability to control HIV replication is lost. Conversely, HAART initiation occurring within three weeks from the infection could allow to preserve a significant control capability. This time could be related to the global triggering of uncontrolled immune activation, affecting residual immune competence preservation and HIV reservoir establishment.