Contraceptive Hormonal Induced Changes in the vaginal mucosa – ZIMCHIC study status: Annual Research Day 08 April 2016 DR FG MHLANGA

BACKGROUND Use of hormonal contraceptives, particularly Depo- Provera, has been linked with increased risk of acquiring HIV in some studies but not other studies.

Systematic Review of Injectable use and HIV-1 Acquisition Polis CB, et al. Contraception ↓ HIV Risk ↑ HIV Risk

Oct 2011

Is the relationship causal or casual? The reason for the increased risk may be behavioural or biological The Evidence for Contraception & HIV Outcomes (ECHO) Study is a Randomized Control study whose aim is to assess whether hormonal contraception increases the risk of HIV acquisition amongst Depo- Provera, Jadelle & IUCD users The ZIMCHIC study complementary to the ECHO Trial

The ZIMCHIC study Seeks to assess the biological effect of contraceptives in the female genital tract, particularly to observe if entry points (target cells) for HIV are altered. Also seeks to assess if the innate immunity (non-specific body defence system against infection) is altered by contraceptives. HIV entry into the body requires evading the innate immunity and attaching to entry/target cells. Focus on the genital tract acknowledges that >90% of HIV infection is spread through heterosexual contact

How was the ZIMCHIC study done? Enrolled hormone free (some needed a washout period) women aged years They selected into any of the six available long acting contraceptive arms Depo medroxyprogesterone acetate (DMPA) N=50 NET-EN N=50 MPA/E2 (Cyclofem) N=50 LNG-I (Jadelle) N=50 Copper IUD (Cu-IUD) N=50 Etonogestrel subdermal implant (Implanon) N=50 Follow up visits were at 30, 90 and 180 (exit) days We measured contraceptive hormonal levels in blood as well as HIV target cells in the genital tract at each of these visits.

Study Update The ZIMCHIC study screened 971 women & enrolled 309 of them between 07 February 2014 and 14 December To date all have completed their 90 day visit 66 participants are due for the 180 day visit All efforts are now on retention

Bringing the ZimCHIC Study in for a landing Zim CHIC

Timeline for remainder of study Last study visit will be conducted by mid-to- late June 2016 Plan for relatively quick ‘data lock’ Aug 2016 (or sooner??)

Next Steps Analyses Presentation of data at meetings: Baseline data for Zim vs US women: R4P, Chicago, October 2016 Misrepresentation of contraceptive use: Forum in Family Planning, Denver, November 2016 Primary outcome: CROI 2017? (submission late September 2016) Satisfaction with LARCs in Zimbabwean women: international Family Planning meeting 2017