Fig. 1.

Design of the macaque MZCL IVR study. (a, b) Graphical representation of the MZCL IVR. The thermoplastic matrix containing MIV-150 and LNG encompasses the compressed core of CG and ZA. A pore (500 or 800 μm) drilled through the matrix to the core exposes the core to incoming vaginal fluid, allowing hydration of the core and release of CG and ZA. (c) A repeated SHIV-RT/HSV-2 co-challenge model was used for testing the MZCL IVR. IVRs were inserted into rhesus macaques not treated with DMPA for 21 d before they were exchanged for new IVRs for a total of 5 IVR cycles over 105 d. Co-challenge with 200 TCID₅₀ SHIV-RT and 10⁷ pfu HSV-2 occurred on d7, 10, 14, and, 17 of each IVR cycle. PK time points were on d9 and d16 of the first (IVR-1) and fifth (IVR-5; this corresponds to d93 and d100 of the entire study for IVR-5) IVR cycles as well as post-removal (PR) of IVR-5 (0 h PR). Blood was collected at additional time points post-insertion of IVR-1 and IVR-5 and also 4 h PR of IVR-5