Article Text

PDF

S14.3 Immune activation, gene expression and hiv acquisition risk
  1. KR Fowke1,2,3,
  2. G Boily-Larouche1,
  3. L Mwangi2,4,
  4. J Mungai4,
  5. M Akolo4,
  6. M Kimani4,
  7. J Oyugi1,2,3,
  8. J Kimani1,2,3,4,
  9. J Lajoie1
  1. 1Department of Medical Microbiology, University of Manitoba
  2. 2Department Medical Microbiology, University of Nairobi
  3. 3Deparment of Community Health Science, University of Manitoba
  4. 4Kenyan AIDS Control Program

Abstract

Background Sexual transmission of HIV is actually fairly inefficient and when it does occur usually a single virus is responsible for establishing the infection.  Since activated HIV target cells (CD4+CCR5+) are known to be 1000x more susceptible to HIV infection than quiescent cells, one of the known risk factors for HIV acquisition is elevated baseline levels of immune activation.  This study was designed to determine if oral administration of low doses of anti-inflammatory agents, acetylsalicylic acid (ASA) and hydroxychloroquine (HCQ), would reduce the number of HIV target cells in the female genital tract. 

Methods 80 low-risk women from Nairobi, Kenya established baseline immune activation levels and then were randomized to 6 weeks oral administration of low doses of either ASA (81 mg/day) or HCQ (200 mg/day).  Cellular activation (CD69, HLA-DR, CD95, CCR5) was assessed by flow cytometry of peripheral blood mononuclear cells (PBMC) and cervical mononuclear cells (CMC). 

Results In PBMCs, a reduction in the percentage of CD4+CD69+ (p = 0.01) and CD4+CCR5+ (p = 0.03) T cells was observed in the ASA arm and a significant decrease of CD95 (p < 0.0001) and CCR5 (p = 0.01) expression on CD4+ T cells was observed following HCQ treatment.  At the mucosal level, CMCs showed reduced levels  of CD4+CCR5+ T cells following ASA treatment (p -0.02) and lower expression of the activation marker CD69 on CD4+ cells in the HCQ arm (p = 0.05).

Conclusions Reducing the number of HIV target cells in the female genital tract, represents a new approach to reducing HIV risk.  This study showed that daily administration of low-dose anti-inflammatory drugs reduces the number of HIV target cells in the female genital tract.  Further studies are required to determine if a similar reduction in mucosal HIV target cells can be observed in women at high-risk of acquiring HIV and if those reduction provide any protective benefit.

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.