2 Recruit women willing to initiate use of the LARC method Randomize women in equal proportions “Immediate” LARC arm: Start LARC method Collect vaginal swab “Delayed” LARC arm: • Collect vaginal swab Follow-up visits Collect vaginal swab Last follow-up visit Collect vaginal swab Start LARC method for those in “delayed” LARC arm Figure 1: Proposed study schema. condoms only [10]. A case-control study of adolescents in Texas found that condom use among implant users was lower than among oral contraceptive users [11]. Three prospective cohort studies also have evaluated the association between LARC and condom use. A study of adolescents in San Francisco found that women who chose to use implants reported less condom use after two years of followup than at baseline [12]. Condom use among implant users was also lower than among those who chose to use oral contraception or condoms alone. In a study conducted in three large urban hospitals of 1,073 women initiating use of implant or injectable contraception, consistent condom use within the past three months declined after one year of followup [13]. Only one study, conducted among 98 postpartum adolescents in Pennsylvania who chose to use either implants or oral contraception, failed to ﬁnd diﬀerences between groups in the levels of condom use reported [14]. Prior studies on condom migration suﬀer from two main methodological weaknesses: reliance on self-reports of condom use and lack of randomization. Participant reports of condom use could be inaccurate for many reasons, including recall bias or—especially in intervention studies Infectious Diseases in Obstetrics and Gynecology in which condoms are heavily promoted or distributed— social desirability bias [15–18]. Studies that have detected biological markers of semen (e.g., prostate-speciﬁc antigen [PSA] or y-chromosome DNA) in vaginal ﬂuid specimens collected from women who reported no recent exposure suggest substantial underreporting of unprotected sex [19– 24]. Furthermore, misreporting of unprotected sex might not be distributed randomly across a study population, as suggested by a recent study that assessed predictors of discordance between spermatozoa detection and self- reported lack of unprotected sex [25]. For example, if the misreporting of condom use were to diﬀer with respect to the use of other contraceptive methods, the conclusions reached by previous studies on condom migration could be misleading. The second—and perhaps more serious—limitation of past studies involves the lack of randomization for assigning women to method use. Women who choose diﬀerent contraceptive methods often vary by their characteristics [26]. Confounding by indication could occur if the women who choose to use LARC methods (or the women whose providers promote LARC methods to) are predominantly those at low risk of HIV/STIs and, thus, infrequent users of condoms. Those who opt to initiate a LARC method may have inherently diﬀerent patterns of condom use than those who choose not to use the method; thus, earlier studies could be biased as a result of systematic diﬀerences between groups. Few studies on the relationship between use of LARC and condoms have attempted to control for these diﬀerences and thus are subject to confounding; moreover, controlling for these factors would likely be diﬃcult as not all factors inﬂuencing condom use (e.g., perceived HIV/STI risk, ability to negotiate condom use with partner) are known or easily measured. 2. Randomized Controlled Trial Using a Semen Biomarker We propose a randomized design for studying the eﬀect of introducing a speciﬁc type of LARC method (i.e., IUD, IUS, or contraceptive implant) on condom use that addresses both major methodological weaknesses inherent in the previous studies. Under this design, women at risk of pregnancy without contraindications to the method [27, 28] would be randomized to one of two groups: (1) “immediate” start of the LARC method or (2) “delayed” start of the LARC method (i.e., at completion of their last study follow-up visit) (Figure 1). Participants would be asked to complete an enrollment visit and follow-up visits scheduled at regular intervals during the period (e.g., 6–12 months) following enrollment. Vaginal specimens would be collected—either by swabbing by the participant herself or by a study provider— at all study visits for testing for PSA, and participants would be counseled on correct and consistent use of condoms. The study would assess whether use of the LARC method aﬀects the number of unprotected sex acts (i.e., without a condom) as measured by the detection of an objective biomarker of unprotected intercourse, such as PSA, in the vaginal swab.