Genital reservoir: a barrier to functional cure?

HIV functional cure requires the elimination or a major reduction of HIV reservoir pool including male and female genital HIV reservoirs. A comprehensive understanding of HIV dynamics in these compartments is mandatory.

Data from chronically HIV-infected therapy-naïve individuals or fully suppressed on combined antiretroviral therapy (cART) or undergoing ART interruptions are now available. Using paired blood/genital samples, HIV-RNA/DNA quantification and sequencing provide new insights on HIV dynamics in genital reservoirs.

In the absence of cART, HIV shedding in semen and cervicovaginal secretions is frequent, resulting most likely from passive transfer of HIV strains that originates from bloodborne virions or infected blood cells. Partial and intermittent HIV compartmentalization in the male and female genital tracts can occur not only in chronically infected ART-naïve individuals but also when cART is used to prevent active blood replication. This transient autonomous HIV replication in the genital reservoir in a few individuals originates from recent transfer of virions or infected blood cells. cART interruption studies showed that blood and genital quasispecies are closely related, in agreement with a passive transfer. Altogether these data suggest that HIV genital reservoirs seem not to be a significant barrier to achieve HIV cure.