TUSY09 HIV transmission: virus, host and microbiome | Watch the video
Another interesting session I attended today focussed on an exploration of our incomplete understanding of the events that occur at the moment of HIV transmission, looking at the evidence for and implications of the idea of a single founder virus being responsible for mucosal infection, with the likely mechanism being somewhat of a sieve effect of any initial viral inoculum by both host physical and immune mechanisms. In the context of vaginal transmission, this raises the question of whether or not we can use antibiotics and/or probiotic strategies to shift the proinflammatory vaginal mucosal environment caused by the dysbiosis seen in conditions such as bacterial vaginosis toward lactobacillus dominated microbiota to reduce STI and specifically HIV transmission through maintaining an intact mucosal barrier and preventing the bacterial metabolism of ART such as tenofovir.
Commencing the session, Jonathan Carlson of Microsoft presented some intensive modelling data regarding transmission of founder viruses, revealing that this modelling shows that over 80% of HIV infections originate from a single founder virus. Data shows that the presence of multiple founder viruses is seen mostly among high risk exposures characterised by high transmitter viral load, the presence of genital inflammation, and in PWID and MSM, although it may also be seen with virions that do not act independently. With single founder transmission, it seems as though there is a large transmission selection bias with a selection of virions that are closer to (predominant viral variant), with higher infectivity, higher IFN-1 resistance and lower neutralizing antibody resistance. Interestingly, despite increasing the risk of multiple founder viruses, having a higher risk for infection may decrease virion selection pressure and may be associated with a lower viral load.
Smritee Dabee (on behalf of Jo-Ann Passmore) explored in detail the impact of the vaginal microbiome on HIV transmission risk and prevention strategies with a focus on genital tract inflammation as a significant contributor. This was discussed in the context of data showing the relative effectiveness of healthy female genital mucosa as a barrier to HIV entry during vaginal sexual intercourse. In the South African CAPRISA 004 study, it was shown that women who became HIV infected had an odds ratio of 3.2 for cytokine measured pre-infection genital inflammation, with only 20% of HIV infections being attributed to another STI, predominantly trichomonas. Further results from the South African WISH study showed that adolescent females with bacterial vaginosis have higher frequencies of highly activated genital CD4+ cells, which added to HIV infection risk. It will be interesting to see how this information progresses and informs clinical practice, as it was noted that currently there is no clear evidence for the role of vaginal probiotics to rebalance microbiota and reduce HIV transmission risk.