Immunomodulatory effects of cotrimoxazole in HIV infection

• Research type

  Research Study

• Full title

  Characterising the effect of cotrimoxazole on inflammation and immune activation in HIV-infected adults

• IRAS ID

  209553

• Contact name

  Claire Bourke

• Contact email

  c.bourke@qmul.ac.uk

• Sponsor organisation

  Queen Mary University of London

• Duration of Study in the UK

  0 years, 7 months, 2 days

• Research summary

  Cotrimoxazole (CTX) is a broad-spectrum antibiotic that effectively reduces mortality and morbidity in HIV-infected individuals through prevention of common co-infections. CTX prophylaxis is recommended for HIV-infected children and adults globally. In developed countries, CTX can be safely discontinued upon immune reconstitution with antiretroviral therapy (ART), but continuation of CTX shows beneficial reductions in mortality and morbidity in developing countries with high prevalence of serious bacterial infections, irrespective of CD4 count and HIV viral load. Surprisingly CTX efficacy in HIV-infected individuals is retained despite high levels of CTX resistance among targeted pathogens, but it is unclear why CTX remains beneficial in this context.

  One hypothesis is that, in addition to its antimicrobial effects, CTX directly modulates the systemic pro-inflammatory milieu that characterizes HIV infection. Since inflammation and immunodeficiency interact to drive mortality in HIV-infected people, reduced activation of immune cells and lower levels of systemic pro-inflammatory mediators in the blood may have survival benefits. To investigate this, we propose a small observational study enrolling two groups of HIV-infected adults undergoing routine care and one control group of healthy adult volunteers:

  • Group 1 (n=6): HIV-infected, ART-treated >2 years, Viral load <50 copies/mL and not currently taking CTX
  • Group 2 (n=18): HIV-infected, ART-naïve and not currently taking CTX
  • Group 3 (n=6): HIV-uninfected and not currently taking CTX

  The study will involve donation of a single blood sample (Group 1 and Group 3) or two longitudinal blood samples (Group 2) obtained by venepuncture. Blood will be collected at enrollment and ~2 weeks after initiation of treatment with CTX +/- ART (Group 2).

  Blood immune cells will be activated with pro-inflammatory stimuli in vitro in the presence or absence of CTX (all groups) and immune mediators and markers of cell activation will be assayed. Plasma levels of pro-inflammatory markers and circulating antigens will be quantified in all groups at enrollment and in post-treatment samples collected from Group 2.

• REC name

  West Midlands - Solihull Research Ethics Committee

• REC reference

  17/WM/0018

• Date of REC Opinion

  12 Jan 2017

• REC opinion

  Favourable Opinion