Jim K. Aizire, MD, MHS, PhD Johns Hopkins University PEPFAR PROMOTE STUDY High Frequency of Unintended Pregnancy and Predictors of Contraceptive Choice among HIV-infected African Women on Lifelong ART   J. Aizire , N. Yende , T. Nematadzira , M.E. Nyati , S. Dadabhai , L. Chinula , C. Nakaye , M. Naidoo , M.G. Fowler , T. Taha , US-PEPFAR PROMOTE Cohort   Jim K. Aizire, MD, MHS, PhD Johns Hopkins University 26 July 2018

Background Reproductive health burden in sub-Saharan Africa Home to more than 90% of the reproductive health needs globally Women of reproductive age constitute more than 60% of the HIV/AIDS burden Several countries have more than 60% unmet need for modern family planning methods More than 85% of unintended pregnancies are attributed to non-use of an effective family planning (EFP) method (injectable, oral, intra-uterine contraceptive device (IUCD), or Norplant). Most commonly reported reasons for not using EFP include infrequent sex and safety/side-effects. Others include postpartum/breastfeeding, opposition by the partner, as well as access related reasons. Department of Economic and Social Affairs PDUN. Trends in contraceptive use worldwide 2015. Contraception. 2015: Darroch JE et al, Lancet 2013; Darroch JE et al, Responding to Women’s Needs. New York: Guttmacher Institute; 2011 26 July 2018

HIV infected women on ART Study design HIV infected women on ART Standardized procedures across 8 sites in 4 countries (Malawi, Uganda, South Africa and Zimbabwe) Methods Wilcoxon Rank-Sum tests (continuous variables) Poisson regression (with robust variance) to estimate measures of association Chi-square test (categorical variables) SEP 2015 DEC 2016 JUN 2017 PROMISE RCT GAP PEPFAR PROMOTE STUDY 2011 2020 2015 2016 2017 2018 2019 2020 2021 Baseline assessments Follow-up assessments Socio-demographic data Clinical data (reproductive health) Lab data plus stored samples 26 July 2018

High reports of unintended pregnancy (at last conception) Variations by site (P <0.001) (n=249) (n=271) (N=1,985) 26 July 2018

Contraceptive use by country Variations by site (P <0.001) 26 July 2018

Use of Effective Family Planning (EFP) and Long Acting Reversible Contraceptive (LARC) methods EFP methods (injectable, oral, intra-uterine device (IUD), implant, or tubal-ligation).1 LARC methods (implants or IUD) are the most effective, and suitable for women who report infrequent sex, or hormonal side-effects.2 P =<0.001 Department of Economic and Social Affairs PDUN. Trends in contraceptive use worldwide 2015. Contraception. 2015: Darroch JE et al, Lancet 2013; Darroch JE et al, Responding to Women’s Needs. New York: Guttmacher Institute; 2011 26 July 2018

Baseline characteristics (by reported EFP use at study entry) Demographic and socioeconomic factors Characteristic Overall (N=1,295) EFP use (n=1,054) No EFP use (n=241) P value Maternal-age (years), median [IQR] 31 [28-35] 30 [26-35] 0.077 Married/regular partner, n (%) 1,140 (88.0%) 930 (88.2%) 210 (87.1%) 0.936 Unintended pregnancy, n (%) 662 (51.2%) 560 (53.2%) 102 (42.5%) 0.01 Desire another children, n (%) 490 (37.9%) 369 (35.0%) 121 (50.4%) <0.001 No sex in the last 3 months, n (%) 126 (9.7%) 120 (11.4%) 6 (2.5%) Clinic travel time ≥ 1 hour (yes), n (%) 365 (28.2%) 284 (26.9%) 81 (33.8%) 0.588 Education (completed primary), n(%) 1,007 (77.8%) 818 (77.6%) 189 (78.4%) 0.029 Unemployed/housewife, n (%) 588 (45.5%) 477 (45.3%) 111 (46.1%) 0.531 Electricity in household, n(%) 894 (69.0%) 723 (68.6%) 171 (71.0%) 0.173 Currently on ART, n (%) 1,265 (97.7%) 1,030 (97.7%) 235 (97.5%) 0.844 Viral load (>1,000 copies/ml), n (%) 112 (8.9%) 99 (9.6%) 13 (5.7%) Baseline characteristics were homogeneous across LARC groups except: Unemployed women were less likely to report LARC use (p = 0.008) ART users less likely to report LARC use (p=0.001) Viral load (>1000 copies/ml) were less like to report LARC use (p=0.003) 26 July 2018

Correlates of EFP and LARC use at PROMOTE study baseline EFP use LARC use Adjusted RR (95% CI) P value Unintended pregnancy 1.05 (0.99-1.11)  0.086 1.18 (0.93-1.49) 0.174 Desire another child 0.92 (0.87-0.99) 0.017 1.05 (0.81-1.37) 0.703 No sex in last 3 months 0.81 (0.76-0.87) <0.001 0.90 (0.61-1.32) 0.582 Married 1.10 (0.99-1.20) 0.064 0.86 (0.61-1.20) 0.365 Not completed primary school 0.92 (0.85-0.99) 0.03 0.83 (0.61-1.11) 0.202 Housewife/ no formal income 0.94 (0.88-1.00) 0.066 0.66 (0.48-0.91) 0.011 Electricity in household, yes 0.97 (0.91-1.04) 0.419 1.33 (1.01-1.76) 0.04 Clinic travel time ≥ 1 hour 0.401 0.90 (0.68-1.20) 0.486 Viral load, ≤1000 copies/ml 1.10 (1.02-1.19) 0.013 1.64 (1.20-2.23) 0.002 Modified Poisson regression (robust variance estimator); adjusted for age and country 26 July 2018

Future plans/ policy implications Conclusion Future plans/ policy implications Planned PROMOTE cohort analyses Incidence and correlates of unintended pregnancy through 18 months follow-up Interactions between ART (efavirenz) and hormonal contraceptives and risk of unintended pregnancy (quantitative measures of ART and exogenous hormonal levels on stored samples) Policy considerations for HIV infected women on ART Risk of neural tube defects with dolutegravir In this large multinational cohort of HIV infected African women on life-long ART we observed the following at baseline: High prevalence of reported unintended pregnancy (at last conception) About 20% women reported use of non-EFP methods, and only about 20% reported use of LARC methods. There were site variations, with a trend towards one predominant method at site level. Unintended pregnancy at last conception was NOT associated with use of EFP or LARC methods. Tsepamo study, May 2018, and WHO rapid memo 26 July 2018

Acknowledgements The PROMOTE protocol team gratefully acknowledges the dedication and commitment of the more than 1,900 STUDY mothers Sponsors: US PEPFAR (Nareen Abboud) Protocol Chairs : Taha Taha, MG Fowler Statistical and Data Management Center: N, Yende, P Radebe, S Brummel, A Jeewa, N Hua Site PROMOTE Investigators: Blantyre, Malawi B Makanani Lilongwe, Malawi L Chinula Kampala, Uganda M Owor Harare, Zimbabwe T Chipato Soweto, South Africa ME Nyati Durban, South Africa S Hanley

Baseline characteristics (ART regimens used at study entry) No reported use of dolutegravir 26 July 2018

Correlates of EFP and LARC use at PROMOTE study baseline EFP use LARC use Adjusted RR (95% CI) P value Unintended pregnancy 1.05 (0.99-1.11)  0.086 1.18 (0.93-1.49) 0.174 Desire another child 0.92 (0.87-0.99) 0.017 1.05 (0.81-1.37) 0.703 No sex in last 3 months 0.81 (0.76-0.87) <0.001 0.90 (0.61-1.32) 0.582 Married 1.10 (0.99-1.20) 0.064 0.86 (0.61-1.20) 0.365 Not completed primary school 0.92 (0.85-0.99) 0.03 0.83 (0.61-1.11) 0.202 Housewife/ no formal income 0.94 (0.88-1.00) 0.066 0.66 (0.48-0.91) 0.011 Electricity in household, yes 0.97 (0.91-1.04) 0.419 1.33 (1.01-1.76) 0.04 Clinic travel time ≥ 1 hour 0.401 0.90 (0.68-1.20) 0.486 Viral load, ≤1000 copies/ml 1.10 (1.02-1.19) 0.013 1.64 (1.20-2.23) 0.002 Modified Poisson regression (robust variance estimator); adjusted for age and country 26 July 2018