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

Carlum Shiu, Coleen K. Cunningham, Thomas Greenough, Petronella Muresan, Victor Sanchez-Merino, Vincent Carey, J. Brooks Jackson, Carrie Ziemniak, Lawrence Fox, Marvin Belzer, Stuart C. Ray, Katherine Luzuriaga, Deborah Persaud

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)9731-9742
Number of pages12
JournalJournal of virology
Volume83
Issue number19
DOIs
StatePublished - Oct 2009

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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