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Stable HIV-1 integrase diversity during initial HIV-1 RNA Decay suggests complete blockade of plasma HIV-1 replication by effective raltegravir-containing salvage therapy

Marc Noguera-Julian1*, Maria Casadellà1, Christian Pou1, Cristina Rodríguez1, Susana Pérez-Álvarez1, Jordi Puig2, Bonaventura Clotet123 and Roger Paredes123

Author Affiliations

1 IrsiCaixa AIDS Research Institute-HIVACAT, Hospital Universitari Germans Trias I Pujol, Ctra de Canyet s/n, Badalona 08916, Catalonia, Spain

2 HIV Unit&Fundació Lluita contra la SIDA Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain

3 Universitat Autònoma de Barcelona, Badalona, Catalonia, Spain

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Virology Journal 2013, 10:350  doi:10.1186/1743-422X-10-350

Published: 5 December 2013

Abstract

Background

There is legitimate concern that minority drug-resistant mutants may be selected during the initial HIV-1 RNA decay phase following antiretroviral therapy initiation, thus undermining efficacy of treatment. The goal of this study was to characterize viral resistance emergence and address viral population evolution during the first phase of viral decay after treatment containing initiation.

Findings

454 sequencing was used to characterize viral genetic diversity and polymorphism composition of the HIV-1 integrase gene during the first two weeks following initiation of raltegravir-containing HAART in four ART-experienced subjects. No low-prevalence Raltegravir (RAL) drug resistance mutations (DRM) were found at baseline. All patients undergoing treatment received a fully active ART according to GSS values (GSS ≥ 3.5). No emergence of DRM after treatment initiation was detected. Longitudinal analysis showed no evidence of any other polymorphic mutation emergence or variation in viral diversity indexes.

Conclusions

This suggests that fully active salvage antiretroviral therapy including raltegravir achieves a complete blockade of HIV-1 replication in plasma. It is unlikely that raltegravir-resistant HIV-1 may be selected in plasma during the early HIV-1 RNA decay after treatment initiation if the administered therapy is active enough.

Keywords:
HIV-1; Raltegravir; Dynamics; Deep sequencing