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Amplifying and Quantifying HIV-1 RNA in HIV Infected Individuals with Viral Loads Below the Limit of Detection by Standard Clinical Assays
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Temporal Patterns and Drug Resistance in CSF Viral Escape Among ART-Experienced HIV-1 Infected Adults.

Shibani S Mukerji1, Vikas Misra, David Lorenz

  • 1*Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA; †Department of Neurology, Massachusetts General Hospital, Boston, MA; ‡Departments of Neurology and Neurosurgery, Boston Medical Center, Boston, MA; §Department of Neurology, Brigham and Womens Hospital, Boston, MA; ‖Division of NeuroImmunology, Beth Israel Deaconess Medical Center, Boston, MA; ¶Department of Geographic Medicine and Infectious Diseases, Tufts Medical Center, Boston, MA; #Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY; and **Department of Neurological Sciences, Rush University Medical Center, Chicago, IL.

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Cerebrospinal fluid (CSF) viral escape in HIV-1 patients on antiretroviral therapy is linked to longer infection duration and specific mutations. Understanding these patterns aids in identifying causes and developing new treatments.

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Area of Science:

  • Neurovirology
  • Infectious Diseases
  • HIV/AIDS Research

Background:

  • Cerebrospinal fluid (CSF) viral escape is a growing concern in adults with HIV-1 on antiretroviral therapy.
  • This phenomenon involves discordant HIV-1 RNA levels between CSF and plasma.

Purpose of the Study:

  • To analyze longitudinal data and drug-resistance mutations.
  • To characterize HIV-1 patients with discordant CSF and plasma viral RNA levels.

Main Methods:

  • Analysis of 41 cases of CSF escape from Boston Hospitals and the National NeuroAIDS Tissue Consortium (NNTC) between 2005 and 2016.
  • Classification of cases based on preceding plasma HIV-1 RNA levels (high-level viremia, low-level viremia, plasma suppression).
  • Identification of drug-resistance mutations, particularly M184V/I.

Main Results:

  • Estimated CSF escape prevalence was 6.0% and 6.8% in the studied cohorts.
  • Patients were median 50 years old with a median 17-year duration of HIV-1 infection.
  • Neurological symptoms were present in 30 cases; 75% of repeat CSF escape cases had low-level viremia.
  • M184V/I mutations were found in 74% of CSF samples when plasma viral load was ≤50 copies/mL.

Conclusions:

  • CSF escape is frequently associated with over 15 years of HIV-1 infection, prior low-level viremia, and M184V/I mutations in CSF.
  • Classifying cases by preceding plasma HIV RNA levels offers a framework for identifying causal factors and therapeutic targets.