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Impact of antiretroviral therapy in the gut bacterial resistome

Description

Researchers will test the following hypotheses:

  • Different antiretroviral drugs, particularly, but not limited to, nucleoside analogues, may have antibacterial activity.
  • Antiretroviral drugs that induce mutations in gut commensal bacteria and pathogenic strains can impact susceptibility to antibacterial agents and increase antimicrobial resistance.
  • HIV-1 associated immune deterioration, cotrimoxazole (TMP-STX) prophylaxis, antiretroviral treatment (ART) initiation and immune recovery under ART may have different impacts on the gut resistome of HIV-1-infected patients. Such impacts remain poorly understood and can only be disentangled through adequately controlled prospective clinical trials. Indirect evidence of one such impact is that Escherichia coli isolates from urinary tract infections are more likely to be resistant to TMP-STX, ciprofloxacin and mecillinam in HIV-infected subjects than in the general population.
  • Immune reconstitution is associated with reduced gut microbiome antimicrobial resistance. It is unknown in whether gut microbiome changes associated with low levels of CD4+ T-cells can be reversed or whether they are more relevant than recent CD4+ counts in determining the structure of the gut microbial resistome.
  • Probiotics may favour the displacement of multidrug-resistant bacteria which, in general, have a fitness cost and so could be easily replaced.

Objectives

Researchers will analyse the impact on the gut microbiota resistome of the following factors: immune reconstitution, exposure to different ARTs, exposure to and interruption of cotrimoxazole prophylaxis and exposure to commercial probiotics and synbiotics. The main objectives are as follows:

  • To define the phenotypic and clinical correlates of shotgun metagenomics-based gut bacterial resistome analyses.
  • To evaluate whether different antiretroviral drugs show antibacterial activity and whether, in vitro, they could select for antibiotic drug-resistant mutants in selected bacterial pathogens.
  • To investigate the impact of immune reconstitution and exposure to different ARTs on the gut bacterial resistome.
  • To evaluate the effect of exposure to and interruption of cotrimoxazole prophylaxis on the gut bacterial resistome.
  • To evaluate whether oral supplementation with a probiotic or synbiotic could displace multidrug resistant bacteria from the gut microbiota.

INSTITUTIONS

IrsiCaixa Institut de Recerca de la Sida Case Western Reserve University IDIBAPS ISGlobal Barcelona Institute for Global Health

LEAD BENEFICIARY

ISGlobal Barcelona Institute for Global Health