Genotypic Analysis of HIV-1 Drug Resistance at the Limit of Detection: Virus Production without Evolution in Treated Adults with Undetectable HIV Loads (original) (raw)

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1

Departments of Medicine, Johns Hopkins University School of Medicine

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Baltimore, Maryland

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1

Departments of Medicine, Johns Hopkins University School of Medicine

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Baltimore, Maryland

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1

Departments of Medicine, Johns Hopkins University School of Medicine

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Baltimore, Maryland

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1

Departments of Medicine, Johns Hopkins University School of Medicine

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Baltimore, Maryland

5

National Institutes of Allergy and Infectious Diseases, National Institutes of Health

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Bethesda, Maryland

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Department of Biostatistics, Johns Hopkins University School of Public Health

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Baltimore, Maryland

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Departments of Medicine, Johns Hopkins University School of Medicine

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Baltimore, Maryland

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Departments of Pediatrics, Johns Hopkins University School of Medicine

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Baltimore, Maryland

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Departments of Medicine, Johns Hopkins University School of Medicine

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Baltimore, Maryland

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Howard Hughes Medical Institute, Johns Hopkins University School of Medicine

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Baltimore, Maryland

Reprints or correspondence: Dr. Robert F. Siliciano,

Dept. of Medicine, Johns Hopkins University School of Medicine

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1049 Ross Bldg., 720 Rutland Ave., Baltimore MD 21205

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Received:

12 September 2003

Accepted:

04 November 2003

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Tara L. Kieffer, Mariel M. Finucane, Richard E. Nettles, Thomas C. Quinn, Karl W. Broman, Stuart C. Ray, Deborah Persaud, Robert F. Siliciano, Genotypic Analysis of HIV-1 Drug Resistance at the Limit of Detection: Virus Production without Evolution in Treated Adults with Undetectable HIV Loads, The Journal of Infectious Diseases, Volume 189, Issue 8, 15 April 2004, Pages 1452–1465, https://doi.org/10.1086/382488
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Abstract

Human immunodeficiency virus (HIV) production continues in patients receiving highly active antiretroviral therapy (HAART) with undetectable (<50 copies/mL) virus loads. Our initial cross-sectional study showed that this viremia is composed of viruses that lack new resistance mutations to the HAART regimen. Here we describe a longitudinal, clonal genotypic analysis of plasma virus loads in treated adults who had undetectable virus loads. We document a continuous production of virus in 8 HIV-1-infected adults who maintained suppression of viremia for up to 15 months. Using analytical approaches for distinguishing selected resistance mutations from nonselected mutations and polymerase chain reaction errors, we detected no evolution of resistance in the reverse-transcriptase and protease genes. Sporadic resistance mutations were detected in some viral clones that were not selected for subsequently. Thus, in some patients, HAART suppresses replication to a level that does not allow the evolution of drug resistance over a time frame of years.

© 2004 by the Infectious Diseases Society of America

Topic:

• polymerase chain reaction
• hiv
• mutation
• antiretroviral therapy, highly active
• drug resistance
• adult
• clone cells
• endopeptidases
• genotype
• hiv-1
• plasma
• rna-directed dna polymerase
• viremia
• viruses
• peptide hydrolases
• limit of detection

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