Tenofovir (TDF)-selected or abacavir (ABC)-selected low-frequency HIV type 1 subpopulations during failure with persistent viremia as detected by ultradeep pyrosequencing

Richard T. D'Aquila, Anna Marie Geretti, Joseph H. Horton, Elizabeth Rouse, Asghar Kheshti, Stephen Raffanti, Katrina Oie, Keith Pappa, Lisa L. Ross

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Detection of drug resistance is critical for determining antiretroviral treatment options. Ultradeep pyrosequencing (UDPS; 454 Life Sciences) is capable of detecting virus variant subpopulations with much greater sensitivity than population sequencing, which typically has a detection limit around 20%. UDPS of the HIV-1 reverse transcriptase (RT) (amino acids 56-120) was performed to detect the key mutations K65R and L74V associated with tenofovir and abacavir use. Plasma specimens from subjects with persistent rebound viremia following suppression on tenofovir (n = 8) or abacavir (n = 9)-based therapy were studied. Samples from a subject treated with zidovudine/lamivudine/efavirenz with a similar loss of virologic response served as a control. HIV-1 plasma RNA was ≥3.68 log10 copies/ml at all time points sequenced. The median number of UDPS sequences analyzed/time point was 33,246. Among the eight tenofovir-treated subjects, three showed high-frequency (>20%) RT K65R at the time of failure, whereas one showed low-frequency (<20%) L74V; no low-frequency K65R was detected in these subjects. Among the nine abacavir-treated subjects, three showed low-frequency K65R; no L74V was detected in these patients. No K65R or L74V was detected in the samples from the control subject. At failure, other RT mutations were detected, including low-frequency NNRTI-resistant species detected at ≥1 time point in nine subjects; the key NNRTI mutation K103N, however, was always observed at >20% frequency. Although UDPS is useful in the detection of low-frequency subpopulations with transmitted resistance in antiviral-naive patients, it may have less utility in treatment-experienced patients with persistent viremia on therapy.

Original languageEnglish (US)
Pages (from-to)201-209
Number of pages9
JournalAIDS research and human retroviruses
Volume27
Issue number2
DOIs
StatePublished - Feb 1 2011

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Infectious Diseases

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