Individuals with HIV-1 Subtype C Infection and Cryptococcal Meningitis Exhibit Viral Genetic Intermixing of HIV-1 Between Plasma and Cerebrospinal Fluid and a High Prevalence of CXCR4-Using Variants

AIDS Res Hum Retroviruses. 2018 Jul;34(7):607-620. doi: 10.1089/AID.2017.0209. Epub 2018 May 23.

Abstract

The genotypic properties of human immunodeficiency virus type 1 (HIV-1) subtype C in individuals presenting with cryptococcal meningitis (CM) are not well established. Employing single-genome amplification as well as bulk PCR, cloning and sequencing strategies, we evaluated the genetic properties of HIV-1 subtype C env in 16 antiretroviral therapy-naive study participants with CM. Eleven of the 16 participants had matched blood plasma and cerebrospinal fluid (CSF) evaluated, with the rest having either a plasma or CSF sample evaluated. Before antiretroviral therapy initiation, matched plasma and CSF-derived env sequences of all 11 participants displayed genetic intermixing between the two compartments. Overall, 7 of the 16 (∼43.8%) participants harbored CXCR4-using variants in plasma and/or CSF, according to coreceptor usage prediction algorithms. This study suggests that HIV-1 subtype C genetic intermixing between peripheral blood and the central nervous system is common in individuals presenting with CM, and that CXCR4 usage is present in one or both compartments in approximately 44% of individuals.

Keywords: HIV-1; cerebrospinal fluid; cryptococcal meningitis; plasma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cerebrospinal Fluid / virology*
  • Cloning, Molecular
  • Female
  • Genetic Variation*
  • Genotype
  • HIV Infections / complications*
  • HIV Infections / virology*
  • HIV-1 / classification*
  • HIV-1 / genetics
  • HIV-1 / isolation & purification
  • Humans
  • Male
  • Meningitis, Cryptococcal / complications*
  • Middle Aged
  • Plasma / virology*
  • Polymerase Chain Reaction
  • Prevalence
  • Prospective Studies
  • Receptors, CXCR4
  • Sequence Analysis, DNA
  • Young Adult
  • env Gene Products, Human Immunodeficiency Virus / genetics

Substances

  • CXCR4 protein, human
  • Receptors, CXCR4
  • env Gene Products, Human Immunodeficiency Virus