HIV-1 replication and immune dynamics are affected by raltegravir intensification of HAART-suppressed subjects

Maria J Buzón, Marta Massanella, Josep M. Llibre, Anna Esteve, Viktor Dahl, Maria C. Puertas, Josep M. Gatell, Pere Domingo, Roger Paredes, Mark E Sharkey, Sarah Palmer, Mario Stevenson, Bonaventura Clotet, Juli Blanco, Javier Martinez-Picado

Research output: Contribution to journalArticle

387 Citations (Scopus)

Abstract

Highly active antiretroviral therapy (HAART) results in potent and durable suppression of HIV-1 viremia. However, HIV-1 replication resumes if therapy is interrupted. Although it is generally believed that active replication has been halted in individuals on HAART, immune activation and inflammation continue at abnormal levels, suggesting continued, low-level viral replication. To assess whether active replication might be driving immune activation in HAART, we examined the impact of treatment intensification with the integrase inhibitor raltegravir on viral complementary DNA and immune activation parameters. In the presence of raltegravir, linear HIV-1 cDNA is prevented from integrating into chromatin and is subsequently converted to episomal cDNAs. Raltegravir intensification of a three-drug suppressive HAART regimen resulted in a specific and transient increase in episomal DNAs in a large percentage of HAART-suppressed subjects. Furthermore, in subjects with these episomal DNAs, immune activation was higher at baseline and was subsequently normalized after raltegravir intensification. These results suggest that, despite suppressive HAART, active replication persists in some infected individuals and drives immune activation. The ability of raltegravir intensification to perturb the reservoir that supports active replication has implications for therapeutic strategies aimed at achieving viral eradication.

Original languageEnglish
Pages (from-to)460-465
Number of pages6
JournalNature Medicine
Volume16
Issue number4
DOIs
StatePublished - Apr 1 2010
Externally publishedYes

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Highly Active Antiretroviral Therapy
HIV-1
Chemical activation
Complementary DNA
Integrase Inhibitors
DNA
Viremia
Viral DNA
Chromatin
Raltegravir Potassium
Therapeutics
Inflammation
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

J Buzón, M., Massanella, M., Llibre, J. M., Esteve, A., Dahl, V., Puertas, M. C., ... Martinez-Picado, J. (2010). HIV-1 replication and immune dynamics are affected by raltegravir intensification of HAART-suppressed subjects. Nature Medicine, 16(4), 460-465. https://doi.org/10.1038/nm.2111

HIV-1 replication and immune dynamics are affected by raltegravir intensification of HAART-suppressed subjects. / J Buzón, Maria; Massanella, Marta; Llibre, Josep M.; Esteve, Anna; Dahl, Viktor; Puertas, Maria C.; Gatell, Josep M.; Domingo, Pere; Paredes, Roger; Sharkey, Mark E; Palmer, Sarah; Stevenson, Mario; Clotet, Bonaventura; Blanco, Juli; Martinez-Picado, Javier.

In: Nature Medicine, Vol. 16, No. 4, 01.04.2010, p. 460-465.

Research output: Contribution to journalArticle

J Buzón, M, Massanella, M, Llibre, JM, Esteve, A, Dahl, V, Puertas, MC, Gatell, JM, Domingo, P, Paredes, R, Sharkey, ME, Palmer, S, Stevenson, M, Clotet, B, Blanco, J & Martinez-Picado, J 2010, 'HIV-1 replication and immune dynamics are affected by raltegravir intensification of HAART-suppressed subjects', Nature Medicine, vol. 16, no. 4, pp. 460-465. https://doi.org/10.1038/nm.2111
J Buzón, Maria ; Massanella, Marta ; Llibre, Josep M. ; Esteve, Anna ; Dahl, Viktor ; Puertas, Maria C. ; Gatell, Josep M. ; Domingo, Pere ; Paredes, Roger ; Sharkey, Mark E ; Palmer, Sarah ; Stevenson, Mario ; Clotet, Bonaventura ; Blanco, Juli ; Martinez-Picado, Javier. / HIV-1 replication and immune dynamics are affected by raltegravir intensification of HAART-suppressed subjects. In: Nature Medicine. 2010 ; Vol. 16, No. 4. pp. 460-465.
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