Mucosal effects of tenofovir 1% gel wane over longer-term use but retain pro-proliferative and type I/III interferon pathway signatures [MTN014_15cmRectum]

The nucleotide reverse transcriptase inhibitor (NRTI) tenofovir has been extensively tested as a topical preventative against vaginal and rectal HIV transmission. We sought to determine how use of this product affects gene expression. We used samples from MTN-014, a study of vaginal and rectal gel application. We obtained rectal biopsies before treatment initiation and after two weeks of daily use of tenofovir 1% gel applied rectally or vaginally. We isolated RNA from rectal biopsies preserved with RNAlater. Gene expression was measured from all three samples (three time points) from each participant. Gene expression was measured by Illumina HumanHT-12 v4 Expression BeadChips. Samples were paired with samples taken at baseline (pre-treatment) and after two weeks of daily gel use. Rectal and vaginal biopsies were preserved with RNAlater at -80 degrees C. Samples were not replicated on the arrays. During quality control assessment, two pairs of samples were determined by gene expression profiles to have been switched. In both cases, the pairs were physically adjacent during sample processing and the sample labeled “rectum” had gene expression consistent with vagina and vice versa. The two pairs are B11 (GSM8520898)/B12 (GSM8520862) and D10 (GSM8520864)/D11 (GSM8520894). The labeling has been corrected here so that the samples match their gene expression profiles.