Journal Article

HIV Type 1 Fitness Evolution in Antiretroviral-Experienced Patients with Sustained CD4<sup>+</sup> T Cell Counts but Persistent Virologic Failure

Julia G. Prado, Neil T. Parkin, Bonaventura Clotet, Lidia Ruiz and Javier Martinez-Picado

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 41, issue 5, pages 729-737
Published in print September 2005 | ISSN: 1058-4838
Published online September 2005 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/432619
HIV Type 1 Fitness Evolution in Antiretroviral-Experienced Patients with Sustained CD4+ T Cell Counts but Persistent Virologic Failure

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  • Immunology
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Background. Over recent years, treatment guidelines for human immunodeficiency virus (HIV) infection have evolved from monotherapy to combination regimens that include ⩾3 active drugs, resulting in a sharp decrease in morbidity and mortality. In the present article, we evaluated changes in HIV type 1 viral fitness associated with the sequential introduction of antiretroviral treatment strategies in 4 chronically infected patients with sustained CD4 cell count despite having a persistently detectable viral load.

Methods. Plasma samples were obtained before and during treatment to construct recombinant virus containing the 3′-end of gag, the protease and the reverse-transcriptase coding region. Drug susceptibility phenotype was evaluated with a panel of multiple reverse-transcriptase and protease inhibitors. Replicative capacity (RC) and infectivity were measured, and production of p24 was monitored after transfection.

Results. Multidrug-resistant (MDR) viruses selected during long-term antiretroviral therapy were less fit and infectious than their wild-type or monotherapy-selected counterparts, with the exception of viruses recovered from patient B. In 3 of 4 cases, p24 kinetics after transfection showed a delay in viral production of recombinant viruses containing MDR mutations. Data from the RC and infectivity assays showed good correlation (P < .03) and corroborated the p24 kinetics data.

Conclusions. This study shows that accumulation of MDR mutations during long-term antiretroviral treatment results, albeit not in all cases, in reductions of viral fitness.

Journal Article.  4813 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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