Tenofovir regimen with levonorgestrel vaginal ring safe, effective in women

A 90-day tenofovir (TFV) regimen combined with a levonorgestrel (LNG) intravaginal ring (IVR), which elutes the drug continuously or cyclically, is safe for use in women and can effectively prevent unintended pregnancies, a recent phase I study has found.

Researchers enrolled 47 women who were randomly allocated to four arms. Women received the TFV/LNG intervention at either continuous or cyclical dosing, or the corresponding placebos. Safety outcomes included adverse events and changes in mucosal histology and immune mediators from baseline.

All IVRs were deemed safe. There were no recorded serious adverse events and genital tract histology remained largely normal. The same was true for immune cell density and the secretion of soluble proteins.

The intervention regimen resulted in median vaginal fluid TFV concentrations exceeding 500 ng/mg through 90 days of follow-up. Meanwhile, the average serum LNG concentration was above 200 pg/mL within 2 hours of TFV/LNG initiation, while levels of TFV-diphosphate in tissues increased beyond 1,000 fmol/mg within 72 hours after IVR insertion.

Of note, women assigned to the IVR group showed significantly stronger vaginal fluid inhibitory activity against HIV, jumping to 87 percent to 98 percent as opposed to only 10 percent at baseline (p<0.01). Similarly, anovulation was significantly higher in IVR users, while abnormal cervical mucus sperm penetration was lower.

“Drug release from the IVRs achieved high local concentrations and low plasma levels, minimizing potential systemic adverse events,” the researchers said.