Dr. Maricianah Onono

2. Comparison of pregnancy incidence among African women in a randomized trial of intramuscular depot medroxyprogesterone acetate (DMPA-IM), copper intrauterine device (IUD),and levonorgestrel (LNG) implant Dr. Maricianah Onono @Maricianah Share your thoughts on this presentation with #IAS2019

3. Co-author acknowledgement • Kavita Nanda • Kate Heller • Doug Taylor • Peter Gichangi • Renee Heffron • Margaret Kasaro • Cheryl Louw • Charles Morrison • Nelly Mugo • Zelda Nhlabatsi • Jenni Smit • Imelda Wakhungu • Irina Yacobson • Jared Baeten  On behalf of the ECHO Trial Consortium The authors declare no conflict of interest

4. Background • Sub-Saharan Africa is disproportionately affected by high rates of unintended pregnancy (16 million annually) • Unintended pregnancy can occur due to: • inconsistent or incorrect use of FP method • method non-use • contraceptive failure • Data comparing pregnancy rates with different contraceptive methods as used by women in Sub-Saharan Africa are limited

5. Objectives • This analysis compared pregnancy incidence among women randomized to DMPA-IM, Copper IUD, or LNG implant, which was a protocol-defined objective of the Evidence for Contraceptive options and HIV Outcomes (ECHO) trial • ECHO trial assessed HIV incidence among 7829 women from 12 sites in Eswatini, Kenya, South Africa and Zambia who were: • Seeking effective contraception • Consented to be randomized to DMPA-IM, Copper IUD, or LNG implant

6. Primary Exposure: Contraceptive Use • Only women who initiated their randomized method (RM) were included • Pregnancy analysis was done for perfect use • Perfect use was measured from date women initiated their RM until: • first discontinuation/hold of RM, pregnancy, or last visit with no pregnancy

7. Additional analysis done using typical use • Typical use was measured from date women initiated their RM until: • permanent discontinuation of RM, pregnancy, or last visit with no pregnancy • temporary time off method for any reason (e.g. late or missed DMPA injection, IUD expulsion, clinician-initiated “hold”) counted as typical use

8. Outcome Variable: Incident Pregnancy • Pregnancy testing: • Urine pregnancy test done at first and last visits, and when clinically indicated • Confirmed incident pregnancy: a pregnancy with an estimated date of fertilization after the date of enrollment and on method • Estimated Date of Fertilization • Computed per a standard algorithm, and reviewed by a blinded subcommittee • Calculated as the first day of LMP plus 14 days, or ultrasound date minus gestational age, plus 14 days

9. Results: Demographics and Behavioral Data Previous contraceptive use history: DMPA-IM: 51.0% Implant: 6.4% IUD: 0.8% Median age 23 (range 16-35) Single/ and never married: 79.9% Some or complete secondary education: 74.9% Condom use during the last vaginal sex: 48.2% 1-2 living children: 66.2% • STI prevalence: • Chlamydia trachomatis: 18.1% • Gonorrhea: 4.7% BMI <=30kg/m2: 74.1%

10. Results 7829 women enrolled and followed-up 33 women excluded from analysis due to pregnancy at time of method initiation (15 DMPA-IM, 3 Copper IUD, 15 LNG implant) 86 women excluded from analysis because they never received method(1 DMPA-IM, 79 Copper IUD, and 6 LNG implant) 7710women included in pregnancy analysis 2592 LNG implant 2593 DMPA-IM 2525 Copper IUD

11. Results: Incident Pregnancy 255 pregnancies reported • Median days from randomization to first pregnancy was 96 days for DMPA-IM, 252 days for Copper IUD, and 108 for LNG implant with perfect use 85 pregnancies in typical use 185 pregnancies (72.5%) occurred after women stopped using their contraceptive method 70 pregnancies occurred during perfect use

12. Perfect Use: Cumulative Incidence Curves Pregnancy incidence per 100 WY (95% CI); Pregnancies(n) 1.06 (95%CI 0.72-1.50); n=31 0.63 (95%CI 0.39-0.96); n=21 0.61 (95%CI 0.36-0.96); n=18

13. Risk of Pregnancy in Perfect Use:Comparisons by Randomized Arm *Adjusted for no condom use with last vaginal sex

14. Typical Use Pregnancy Incidence: Comparisons by Randomized Arm *Adjusted for no condom use with last vaginal sex Pregnancy incidence per 100 WY; Pregnancies (n) 1.11 (95%CI 0.77-1.54); n=35 0.87 (95%CI 0.58-1.25); n=29 0.63 (95%CI 0.39-0.96); n=21

15. Conclusion • Both perfect and typical use of all three contraceptive methods resulted in very low pregnancy rates • Women using Copper IUD had somewhat higher pregnancy rates than those using LNG implants and DMPA-IM

16. Conclusion • The DMPA-IM pregnancy incidence with typical use is much lower than has been reported in routine settings, which may be attributed to the proactive tracing by research staff • Higher pregnancy rates with copper IUD may be due to • Lack of ascertainment of fundal placement of the IUD, thus increasing risk of expulsion • Partial or complete expulsions are often asymptomatic or unnoticed thus may not trigger action by both providers or clients

17. Conclusion Our findings provide strong justification to expand access to a range of contraceptive options including LNG implants and Copper IUD for African women at risk of HIV

19. ASANTENI SANA Contraceptive supplies donated by USAID and the Republic of South Africa