Contraceptive Hormone Induced Changes - CHIC UZ-UCSF Annual Research Day Cresta Lodge, Harare 5 May 2017 Allen Matubu

Untangling the mixed data on HC-HIV Two approaches currently underway: Investigation of biological and immunological changes that occur with contraceptive use and that may impact HIV risk (CHIC Studies, Haddad, Dezzutti, etc) Randomized controlled trial (ECHO trial) Women randomized to DMPA, LNG implant, or copper IUD Objective: To assess the impact of contraceptive methods on the numbers and activation status of immune cells in the genital tract Hypothesis for ZimCHIC Study: Women initiating DMPA will have increased cervical HIV target cells compared to baseline after 3 months of use.

Zim CHIC Study Methods Women in Harare, Zimbabwe Healthy Women Ages 18-34 HIV negative Free of STIs (GC, CT, Trichomonas, active HSV) No recent exogenous hormone use (N=451 with self-report) No hormonal or intrauterine contraceptives for >30 days No DMPA for >10 months All in follicular phase of menstrual cycle (day 1-14) and not bleeding Confirmed objectively by UPLC-MS/MS at each visit (N=234) Immune cell populations from PBMCs and cervical cytobrushes were quantified by flow cytometry Baseline and 90-days following initiation of contraceptive Paired changes evaluated with Wilcoxon Signed Rank Gating independently performed by 3 masked scientists Contraception (started immediately after baseline sampling*) Injectables: DMPA, Net-EN, MPA/E2 (N=43, 41 and 36 respectively) Implants: LNG and ENG (N=36 and 37 respectively) IUD: copper (N=41) *DMPA, Net-EN and MPA/EE were administered every 90, 60 and 30 days respectively

Net-EN Use Associated with Local and Systemic Increases in HIV-Target Cells

Copper IUD Use Associated with Local Increases in HIV-Target Cells

Conclusions and Implications Strengths: Population of young, healthy African women Carefully defined with respect to STIs and hormone exposure Paired analyses pre and post exposure Net-EN but not MPA initiation associated with increases in: CCR5 and CD69 on CD4 lymphocytes in PBMCs and cytobrush These data suggest any increased HIV susceptibility associated with MPA may occur through an alternative mechanism Copper IUD initiation associated with increases in: CCR5 and CD69 on CD4 lymphocytes in cytobrush CD11c cells (# and %) in cytobrush IUDs should not be considered as placebos when evaluating the impact of contraceptives on HIV risk No changes in immune cells with LNG or ENG contraceptive implants

Acknowledgements ZimCHIC Participants IRBs-JREC, MRCZ, MCAZ, RCZ Sharon Achilles & Sharon Hillier Prof ZM Chirenje & Dr F Mhlanga ZimChic study Team UZ-UCSF Clinic and Lab Teams