Directly Observed Therapy (DOT) can be Implemented Successfully in Research Settings to Evaluate PrEP PK among Pregnant and Postpartum Adolescents and Young Women in Africa



Daily oral FTC/TDF as pre-exposure prophylaxis (PrEP) can effectively reduce HIV acquisition. However, PrEP efficacy and pharmacokinetics (PK) are poorly understood among pregnant and postpartum women, complicated by the physiological changes women undergo during this period and poor adherence observed in previous oral PrEP studies. Research studies designed to create conditions of near-perfect adherence are advantageous when studying PrEP PK in this population as they eliminate adherence as a confounding variable in PK analysis. We assessed the feasibility of directly observed therapy (DOT), the gold standard metric for adherence, within a clinical research context.


The PK Component of IMPAACT 2009 evaluated the PK characteristics of daily oral PrEP (FTC 200mg/TDF 300mg) among pregnant (enrolled at 14-24 weeks gestation, n=20) and postpartum (enrolled 6-12 weeks after delivery, n=20) young women (16-24 years) in Malawi, South Africa, Uganda, and Zimbabwe. Daily FTC/TDF was administered under direct observation for 12 weeks. Acceptable methods of observation included in-person dosing by study staff, real-time video (e.g., WhatsApp), or recorded timestamped video. DOT implementation was supported through careful staff assignment and training, enhanced participant screening and recruitment, promotion of disclosure to household members, and development of individual, participant-centered, DOT plans.


Forty adolescents and young women (median age: 20 years) were enrolled from March to June 2019; 20 during pregnancy (median gestational age: 18 weeks) and 20 postpartum (median time after delivery: 7 weeks). Of 3360 expected PrEP doses, 3352 (>99%) were directly observed; five doses (<1%) were missed and three (<1%) were taken but not observed. Of the directly observed doses, 3335 (99%) were observed in-person, 13 (<1%) were observed by real-time video, and 4 (<1%) were observed by recorded timestamped video. Of the 40 participants, 34 (85%) achieved perfect adherence (i.e. 100% of expected doses were taken and directly observed).


With appropriate staff preparation and participant support strategies, PK studies with daily DOT can be implemented successfully among African pregnant and postpartum adolescents and young women. Given the complexities in establishing protective PrEP drug levels during pregnancy, this rigorous methodology should be considered in the design of future clinical trials.