Journal article
Identification of Ongoing Human Immunodeficiency Virus Type 1 (HIV-1) Replication in Residual Viremia during Recombinant HIV-1 Poxvirus Immunizations in Patients with Clinically Undetectable Viral Loads on Durable Suppressive Highly Active Antiretroviral Therapy
Journal of virology, Vol.83(19), pp.9731-9742
10/2009
DOI: 10.1128/JVI.00570-09
PMCID: PMC2748010
PMID: 19605490
Abstract
In most human immunodeficiency virus type 1 (HIV-1)-infected individuals who achieve viral loads of <50 copies/ml during highly active antiretroviral therapy (HAART), low levels of plasma virus remain detectable for years by ultrasensitive methods. The relative contributions of ongoing virus replication and virus production from HIV-1 reservoirs to persistent low-level viremia during HAART remain controversial. HIV-1 vaccination of HAART-treated individuals provides a model for examining low-level viremia, as immunizations may facilitate virus replication and sequence evolution. In a phase 1 trial of modified vaccinia virus Ankara/fowlpox virus-based HIV-1 vaccines in 20 HIV-infected young adults receiving HAART, we assessed the prevalence of low-level viremia and sequence evolution, using ultrasensitive viral load (<6.5 copies/ml) and genotyping (five-copy sensitivity) assays. Viral evolution, consisting of new drug resistance mutations and novel amino acid changes within a relevant HLA-restricted allele (e.g., methionine, isoleucine, glutamine, or arginine for leucine at position 205 of RT), was found in 1 and 3 of 20 subjects, respectively. Sequence evolution was significantly correlated with levels of viremia of between 6.5 and <50 copies/ml (
P
= 0.03) and was more likely to occur within epitopes presented by relevant HLA alleles (
P
< 0.001). These findings suggest that ongoing virus replication contributes to low-level viremia in patients on HAART and that this ongoing replication is subject to CD8
+
T-cell selective pressures.
Details
- Title: Subtitle
- Identification of Ongoing Human Immunodeficiency Virus Type 1 (HIV-1) Replication in Residual Viremia during Recombinant HIV-1 Poxvirus Immunizations in Patients with Clinically Undetectable Viral Loads on Durable Suppressive Highly Active Antiretroviral Therapy
- Creators
- Carlum Shiu - Johns Hopkins University, Baltimore, MarylandColeen K Cunningham - Johns Hopkins University, Baltimore, MarylandThomas Greenough - Johns Hopkins University, Baltimore, MarylandPetronella Muresan - Johns Hopkins University, Baltimore, MarylandVictor Sanchez-Merino - Johns Hopkins University, Baltimore, MarylandVincent Carey - Johns Hopkins University, Baltimore, MarylandJ. Brooks Jackson - Johns Hopkins University, Baltimore, MarylandCarrie Ziemniak - Johns Hopkins University, Baltimore, MarylandLawrence Fox - Johns Hopkins University, Baltimore, MarylandMarvin Belzer - Johns Hopkins University, Baltimore, MarylandStuart C Ray - Johns Hopkins University, Baltimore, MarylandKatherine Luzuriaga - Johns Hopkins University, Baltimore, MarylandDeborah Persaud - Johns Hopkins University, Baltimore, Maryland
- Resource Type
- Journal article
- Publication Details
- Journal of virology, Vol.83(19), pp.9731-9742
- DOI
- 10.1128/JVI.00570-09
- PMID
- 19605490
- PMCID
- PMC2748010
- NLM abbreviation
- J Virol
- ISSN
- 0022-538X
- eISSN
- 1098-5514
- Publisher
- American Society for Microbiology (ASM)
- Language
- English
- Date published
- 10/2009
- Academic Unit
- Pathology; VPMA - Administration
- Record Identifier
- 9984046832002771
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