HIV-1 Central Nervous System Compartmentalization and Cytokine Interplay in Non-Subtype B HIV-1 Infections in Nigeria and Malawi

AIDS Res Hum Retroviruses. 2020 Jun;36(6):490-500. doi: 10.1089/AID.2019.0245. Epub 2020 Feb 17.


HIV-1 compartmentalization in the central nervous system (CNS) and its contribution to neurological disease have been well documented. Previous studies were conducted among people infected with subtypes B or C where CNS compartmentalization has been observed when comparing viral sequences in the blood to virus in cerebrospinal fluid (CSF). However, little is known about CNS compartmentalization in other HIV-1 subtypes. Using a deep sequencing approach with Primer ID, we conducted a cross-sectional study among Nigerian and Malawian HIV-1 cohorts with or without fungal Cryptococcus infection diagnosed as cryptococcal meningitis (CM) to determine the extent of CSF/CNS compartmentalization with CM. Paired plasma and CSF samples from 45 participants were also analyzed for cytokine/chemokine levels. Viral populations comparing virus in the blood and the CSF ranged from compartmentalized to equilibrated, including minor or partial compartmentalization or clonal amplification of a single viral sequence. The frequency of compartmentalized viral populations in the blood and CSF was similar between the CM- and CM+ participants. We confirmed the potential to see compartmentalization with subtype C infection and have also documented CNS compartmentalization of an HIV-1 subtype G infection. Cytokine profiles indicated a proinflammatory environment, especially within the CSF/CNS. However, sCD163 was suppressed in the CSF in the presence of CM, perhaps due to elevated levels of IL-4, which were also a feature of the cytokine profile, showing a distinct cytokine profile with CM.

Keywords: CNS compartmentalization; HIV-1; cryptococcal meningitis; cytokine.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Central Nervous System / immunology*
  • Central Nervous System / virology*
  • Cohort Studies
  • Cross-Sectional Studies
  • Cytokines / cerebrospinal fluid
  • Cytokines / immunology*
  • Female
  • HIV Infections / immunology
  • HIV Infections / virology*
  • HIV-1 / classification
  • Humans
  • Malawi
  • Male
  • Meningitis, Cryptococcal / cerebrospinal fluid
  • Meningitis, Cryptococcal / immunology
  • Nigeria
  • Phylogeny
  • RNA, Viral / blood
  • RNA, Viral / cerebrospinal fluid
  • Viral Load
  • Virus Replication


  • Cytokines
  • RNA, Viral