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

2. 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.

3. 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

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

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

6. 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

7. 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