Supplementary Online Content

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1 Supplementary Online Content Mugo NR, Hong T, Celum C, et al; for the Partners PrEP Study Team. Pregnancy incidence and outcomes among women receiving preexposure prophylaxis for HIV prevention: a randomized clinical trial. JAMA. doi: /jama eresults. Search strategy for Medline (using PubMed) efigure 1. Follow-up for the post hoc comparison of tenofovir disoproxil fumarate versus emtricitabine / tenofovir disoproxil fumarate, including initial randomization and re-randomization of the placebo group efigure 2. Serum Creatinine Levels in Infants, by Randomization Group This supplementary material has been provided by the authors to give readers additional information about their work.

2 eresults. Summary of congenital anomalies For pregnancies detected prior to July 2011 (i.e., during the primary, placebo-controlled analysis period): Thirteen infants were born with a total of 17 congenital anomalies. Most anomalies were mild in severity and there was no pattern of anomalies in the PrEP groups. Specifically, the spectrum of anomalies was as follows: tenofovir disproxil fumarate: ankyloglossia congenital (n=1, not causing inference with feeding, resolved prior to assessment in the study clinic by an outpatient release procedure), hypospadias (n=1, without interference with urination, repair deferred by external referral surgeon until age 3), umbilical hernia (n=1, 1 cm, managed conservatively), and ankyloglossia congenital + natal tooth + polydactyly (n=1, ankyloglossia did not interfere with feeding, natal tooth was a single lower left incisor, polydactyly was resolved through an outpatient procedure and was also present in a sibling born prior to the study period); emtrictabine/tenofovir disoproxil fumarate: ankyloglossia congenital (n=1, not causing interference with feeding), syndactyly (n=1, bilateral of 4 th and 5 th digits, there was paternal family history of this same anomaly), Trisomy 21+ talipes equinovarus (n=1, infant was not assessed by the study clinic due to loss to follow-up and information was obtained through maternal verbal report and medical records), omphalocele + ventricular septal defect (n=1, a referral surgeon external to the study team deemed the omphalocele to be amenable to delay repair until at least one year of age, ventricular septal defect was diagnosed by auscultation without clinical signs of cardiac disease); placebo: flat hemangioma (n=1, 5 cm, managed conservatively), hydrocele (n=1, bilateral communicating hydroceles, surgical repair deferred until at least 10 kg in weight), umbilical hernia (n=3, 3 cm, 1 cm, and <1 cm, all managed conservatively). None of the cases of congenital anomaly were considered by the managing clinicians to be related to the study medication. For pregnancies detected after July 2011: An additional five congenital anomalies, occurring in four infants, were observed in pregnancies occurring after July 2011: tenofovir disoproxil fumarate: umbilical hernia (n=2, 2 cm and 1.5 cm, both managed conservatively); emtricitabine/tenofovir disoproxil fumarate: flat hemangioma + umbilical hernia (n=1, hemangioma 2 cm, hernia 1 cm, both managed conservatively), umbilical hernia (n=1, 1 cm, managed conservatively). 2

3 efigure1 legend. efigure 1. Follow-up for the post hoc comparison of tenofovir disoproxil fumarate versus emtricitabine / tenofovir disoproxil fumarate, including initial randomization and rerandomization of the placebo group. Data include all follow-up on active PrEP. In July 2011, the trial s Data and Safety Monitoring Board recommended discontinuation of the placebo group and re-randomization of eligible placebo arm participants to the remaining active PrEP groups. Of 621 female participants initially randomized to placebo, 585 were alive and had not seroconverted to HIV, of whom 74 (12.6%) were deemed ineligible to receive active PrEP, all except one due to ongoing pregnancy and/or breastfeeding (which were exclusion criteria for PrEP provision in the study protocol). Thus, 511 were clinically eligible to receive PrEP, of whom 475 (92.9% of those considered for re-randomization) agreed to receive PrEP and continue in the study, 27 declined further study participation, and 9 had been lost to follow-up. Participants originally assigned to the active PrEP arms were eligible for up to 36 months of follow-up from the time of randomization, with up to 12 months after July 2011; those rerandomized from the placebo arm were eligible for up to 12 months of active PrEP after July Five women contributed no follow-up: 3 initially randomized to tenofovir disoproxil fumarate, 1 initially randomized to emtricitabine/tenofovir disoproxil fumarate, and 1 re-randomized from placebo to emtricitabine/tenofovir disoproxil fumarate. 3

4 65 efigure 1. Follow-up for the post hoc comparison of tenofovir disoproxil fumarate versus emtricitabine / 66 tenofovir disoproxil fumarate, including initial randomization and re-randomization of the 67 placebo group randomized to tenofovir disoproxil fumarate 621 randomized to placebo 566 randomized to combination emtricitabine / tenofovir disoproxil fumarate re-randomized after July re-randomized to tenofovir disoproxil fumarate 238 re-randomized to combination emtricitabine / tenofovir disoproxil fumarate 6m 586/594 (99%) 12m 579/591 (98%) 18m 572/586 (98%) 24m 564/585 (96%) 30m 454/474 (96%) 36m 325/341 (95%) 6m 234/237 (99%) 12m 231/237 (97%) 6m 235/238 (99%) 12m 229/235 (97%) 6m 557/563 (99%) 12m 556/563 (99%) 18m 543/559 (97%) 24m 534/555 (96%) 30m 435/452 (96%) 36m 310/324 (96%) A total of 835 HIV uninfected women were randomized to tenofovir disoproxil fumarate and 832 contributed follow-up, including contributing 174 pregnancies that resulted in 120 live born infants A total of 804 HIV uninfected women were randomized to emtricitabine / tenofovir disoproxil fumarate and 802 contributed follow-up, including contributing 161 pregnancies that resulted in 98 live born infants 4

5 0.8 T reatment arms : T DF F T C /T DF P lacebo 0.7 p= p=0.24 p=0.11 Upper reference range (0.6 mg/dl) S erum creatinine (mg/dl ) p= Lower reference range (0.1 mg/dl) month after birth efigure 2. Serum Creatinine Levels in Infants, by Randomization Groupcategory 3 months after birth Box plots depict median (central line), interquartile range (box), and range (whiskers); numbers below each box indicate the number of subjects. P-value comparisons are each active PrEP group vs placebo, using two sample t tests for the comparisons.