Heterogeneity of HIV-1 replication in ectocervical and vaginal tissue ex vivo

In clinical trials evaluating HIV-1 prevention products, ex vivo exposure of mucosal tissue to HIV-1 is performed to inform drug levels needed to suppress viral infection. Understanding assay and participant variables that influence HIV-1 replication will help with assay implementation. Demographic and behavioral data were obtained from 61 healthy women aged 21-45. Paired cervical (CT) and vaginal (VT) tissue biopsies were collected and treated with HIV-1BaL or HIV-1JR-CSF, washed, and cultured. On days 3, 7, and/or 11, culture supernatant was collected and viral replication was monitored by p24 ELISA. Tissue was extracted at study end and HIV-1 relative RNA copies were determined by PCR. Cumulative p24 and RNA were log-transformed and analyzed using a linear mixed model, t-test, and an intra-class correlation coefficient (ICC). HIV replication was similar between CT and VT for each virus, but HIV-1BaL had 1.5 log10 and 0.9 log10 higher levels of p24 than HIV-1JR-CSF in CT and VT, respectively (p<.001), w...