2IUDnCT Clinical Trial Data (NCT01721798)

Database for analysis presented in forthcoming publication "Safety and continued use of the levonorgestrel intrauterine system as compared with the copper intrauterine device among women living with HIV in South Africa: a randomized controlled trial" in PLoS Medicine. Briefly, in this double-masked, randomized controlled non-inferiority trial, eligible WLHIV were: ages 18–40, not pregnant or desiring pregnancy within 30 months, screened and treated for reproductive tract infections (RTIs) within one month of enrollment, and virologically-suppressed using ART or above treatment threshold at enrollment (non-ART). Between October, 2013, and December, 2016, we randomized consenting women within ART groups, using 1:1 permuted block randomization stratified by ART use, age (18–23, 24–31, 32–40), and recent injectable progestin contraceptive exposure, and provided the allocated IUC. At all visits, participants provided specimens for genital viral load (gVL; primary outcome), plasma viral load (pVL), RTI, and pregnancy testing. We assessed gVL and pVL across six and 24 months controlling for enrollment measures, ART group, age, and RTI using generalized estimating equation and generalized linear models (non-ART group pVL and hemoglobin) in as-treated analyses. We measured IUC discontinuation rates with Kaplan-Meier estimates and Cox proportional hazards models. We enrolled 71 non-ART (36 LNG-IUS, 31 C-IUD; two declined and two were ineligible) and 134 ART-using (65 LNG-IUS, 67 C-IUD; one declined and one could not complete IUC insertion) women. Participant median age was 31 years and 95% had one or more prior pregnancies. Proportions of women with detectable gVL were not significantly different between study arms across six (Adjusted Odds Ratio (AOR): 0.78, 95% Confidence Interval (CI): 0.44–1.38, p=0.39) and 24 months (AOR: 1.03, 95% CI: 0.68–1.57, p=0.88). Among ART users, proportions with detectable pVL were not significantly different at six (AOR=0.83, 95% CI: 0.37–1.86, p=0.65) and 24 months (AOR=0.94, 95% CI: 0.49–1.81, p=0.85), while among non-ART women, mean pVL was not significantly different at six months (-0.10 log10 copies/mL, 95% CI: -0.29–0.10, p=0.50) between LNG-IUS and C-IUD users. IUC continuation was 78% overall; C-IUD users experienced significantly higher expulsion (8% vs 1%, p=0.02) and elective discontinuation (adjusted Hazard Ratio: 8.75, 95% CI: 3.08–24.8, p0.001) rates. Sensitivity analysis adjusted for differential IUC discontinuation found similar gVL results. There were 39 serious adverse events (SAEs); SAEs believed directly related to IUC use (n=7) comprised three pelvic inflammatory disease (PID) cases and four pregnancies with IUC in place with no discernible trend by IUC arm. Mean hemoglobin change was significantly higher among LNG-IUS users across six (0.57 g/dL, 95% CI: 0.24–0.90; p0.001) and 24 months (0.71 g/dL, 95% CI: 0.47–0.95; p0.001).