HIV RNA Screening Reduces Integrase Strand Transfer Inhibitor Resistance Risk in Persons Receiving Long-Acting Cabotegravir for HIV Prevention

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  • Eshleman, S.H.
    • Other Affiliation: Johns Hopkins University School of Medicine
  • Fogel, J.M.
    • Other Affiliation: Johns Hopkins University School of Medicine
  • Halvas, E.K.
    • Other Affiliation: University of Pittsburgh
  • Piwowar-Manning, E.
    • Other Affiliation: Johns Hopkins University School of Medicine
  • Marzinke, M.A.
    • Other Affiliation: Johns Hopkins University School of Medicine
  • Kofron, R.
    • Other Affiliation: University of California, Los Angeles
  • Wang, Z.
    • Other Affiliation: Fred Hutchinson Cancer Research Center
  • Mellors, J.
    • Other Affiliation: University of Pittsburgh
  • McCauley, M.
    • Other Affiliation: FHI 360
  • Rinehart, A.R.
    • Other Affiliation: ViiV Healthcare
  • St Clair, M.
    • Other Affiliation: ViiV Healthcare
  • Adeyeye, A.
    • Other Affiliation: National Institutes of Health
  • Hinojosa, J.C.
    • Other Affiliation: Asociación Civil Selva Amazónica
  • Cabello, R.
    • Other Affiliation: Asociación Via LibreLima
  • Middelkoop, K.
    • Other Affiliation: University of Cape Town
  • Hanscom, B.
    • Other Affiliation: Fred Hutchinson Cancer Research Center
  • Cohen, M.S.
    • School of Medicine, Department of Medicine
  • Grinsztejn, B.
    • Other Affiliation: Instituto de Pesquisa Clinica Evandro Chagas-Fiocruz
  • Landovitz, R.J.
    • Other Affiliation: University of California, Los Angeles
  • HPTN 083 Study Team
Abstract
  • BACKGROUND: The HPTN 083 trial demonstrated that long-acting cabotegravir (CAB-LA) was superior to tenofovir-disoproxil fumarate/emtricitabine for human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP). Integrase strand transfer inhibitor (INSTI) resistance-associated mutations (RAMs) were detected in some participants with HIV infection. We used a low viral load INSTI genotyping assay to evaluate the timing of emergence of INSTI RAMs and assessed whether HIV screening with a sensitive RNA assay would have detected HIV infection before INSTI resistance emerged. METHODS: Single-genome sequencing to detect INSTI RAMs was performed for samples with viral loads <500 copies/mL from 5 participants with previously identified INSTI RAMs and 2 with no prior genotyping results. RESULTS: Major INSTI RAMs were detected in all 7 cases. HIV RNA testing identified infection before major INSTI RAMs emerged in 4 cases and before additional major INSTI RAMs accumulated in 1 case. Most INSTI RAMs were detected early when the viral load was low and CAB concentration was high. CONCLUSIONS: When using CAB-LA PrEP, earlier detection of HIV infection with a sensitive RNA assay may allow for earlier treatment initiation with the potential to reduce INSTI resistance risk. Further studies are needed to evaluate the value and feasibility of HIV RNA testing with CAB-LA PrEP.
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  • Article
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  • In Copyright
Journal title
  • The Journal of infectious diseases
Journal volume
  • 226
Journal issue
  • 12
Page start
  • 2170
Page end
  • 2180
Language
  • English
ISSN
  • 1537-6613
Publisher
  • NLM (Medline)

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