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Defining the genital immune correlates of protection against HIV acquisition: co-infections and other potential confounders
  1. R Kaul1,2,3,
  2. T B Ball2,4,5,
  3. T Hirbod1,6
  1. 1Clinical Science Division, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
  2. 2Department of Medical Microbiology, University of Nairobi, Nairobi, Kenya
  3. 3Department of Medicine, University Health Network, Toronto, Ontario, Canada
  4. 4National HIV and Retrovirology Laboratories, Public Health Agency of Canada, Winnipeg, Canada
  5. 5Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada
  6. 6Department of Medicine, Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden
  1. Correspondence to Dr Rupert Kaul, Clinical Science Division, #6356 Medical Sciences Building, 1 King's College Circle, Toronto, Ontario M5S1A8, Canada; rupert.kaul{at}


The sexual transmission of HIV is very inefficient, presumably because mucosal immune defences prevent infection after most exposures. Since numerous genital immune factors have antiviral effects in vitro, their elucidation might greatly inform the microbicide and HIV prevention fields, particularly in the context of HIV-exposed but persistently seronegative (ESN) individuals. However, several important confounders must be considered in such research. First, sound epidemiological criteria are needed to define individuals as ESN. Then, since high-risk sexual activity is commonly one of these criteria, its potential impact on genital immunology must be carefully considered, both the direct effects of sex and the secondary immune effects of genital co-infections. This means that it may be very difficult to determine whether differences in genital immunology between ESN and control groups are responsible for HIV protection, or are a consequence of high-risk sexual activity. To overcome this confounding, the demographics and epidemiology of ESN cohorts must be described very carefully, thorough co-infection diagnostics must be performed and, if possible, prospective studies with an endpoint of HIV acquisition should be performed to define the direction of causality.

  • AIDS
  • bacterial vaginosis
  • genital infections
  • HIV susceptibility
  • HIV transmission
  • immunology
  • mucosal disease
  • mucosal immunology
  • resistance

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  • Funding This study was funded by theCanadian Institutes of Health Research (RK; HOP-75350 and HET-85518), the Canada Research Chair Programme (RK) and the Swedish International Development Cooperation Agency (TH).

  • Competing interests None.

  • Ethics approval All studies discussed here were reviewed and approved by the relevant research ethical boards at Kenyatta National Hospital, Nairobi, Kenya; the Karolinska Institutet, Stockholm, Sweden; the University of Toronto, Ontario, Canada; and the University of Manitoba, Winnipeg, Canada.

  • Provenance and peer review Commissioned; externally peer reviewed.