Table 1. Key features and overview of linked case studies.

Study acronym: TDF Trials identifier: NCT02995005	Study acronym: DMA Trials identifier: NCT0154248
Study objective: To estimate the time to complete hepatitis B virus (HBV) DNA suppression in HBV DNA positive women who start tenofovir in the late first or early second trimester; and to estimate the proportion of women with HBV DNA at delivery.	Study objective: To determine the efficacy and safety of dihydroartemisinin-piperaquine, artesunate-mefloquine and artemether-lumefrantrine (augmented dose) for treatment of uncomplicated malaria in pregnant women.
Study period: May 2017 –December 2021	Study period: October 2009 –December 2018
Study design: Single arm, open label, tenofovir treatment intervention study.	Study design: Randomised controlled trial, 1:1:1, open label
Phase of trial: Phase IV	Phase of trial: Phase III
Sample size: 170 (actual)	Sample size: 511 (actual)
Participants and criteria     • Pregnant women with estimated gestation of between 12 to 20 weeks. • Aged 16–45 years; and their offspring.	Participant and criteria     • Women with acute uncomplicated malaria, and at 2nd and 3rd trimester of pregnancy.     • Aged 18–45 years; and their offspring.
Study procedures     • Monthly follow up from enrolment until infant is 2 months old.     • Single visit when infant is 4 and 6 months old.     • Venous blood draw monthly for safety (mother kidney and liver test) and HBV viral load in mother and single venous blood draw for baby (at 2 months of age).	Study procedures00     • Up to 4 years of follow-up from enrolment in pregnancy (to infant age 4 years).     • Daily follow-up until malaria smear is negative, then weekly to day 63, then every 1–2 weeks until delivery.     • For infant: in year 1, monthly follow up, and 3 monthly visits thereafter.     • Small volume finger prick samples (x10) for drug level analysis in first 42 days.
Risks     • Risk of liver flare due to disease; risk is increased when the drug is ceased post-partum. Flare is usually biochemical without symptoms, but can be severe and is treatable.	Risks     • All drugs used in the study are recommended by international malaria treatment guidelines.     • The dose of artemether-lumefantrine is higher in the study than in non-pregnant women. There may be side effects related to the higher dose.
Direct benefits, reimbursement, and compensation     • Study population unable to access Tenofovir outside of study and/or unaffordable—cost 1,300 baht (£ 30.17 GBP) per month. Additional cost for liver tests. This is equivalent to 11 days of daily wages earned.     • Participant will be informed of their HBV status.     • Compensated 50 baht (£ 1.15 GBP) per study visit     • Reimbursed for transportation cost for study follow ups.	Direct benefits, reimbursement, and compensation     • Participants will be treated for free with the same drugs. (dihydroartemisinin-piperaquine, artesunate-mefloquine) in the same clinics.     • Compensated 100 baht (£ 2.30 GBP) per study visit.     • Reimbursed for transportation cost for study follow ups.
Potential benefits Exploring pharmacokinetics is critical for maximizing the efficacy and minimizing side effects of any anti-viral interventions during pregnancy.	Potential benefits Findings and data from study will potentially contribute to treatment improvement on uncomplicated malaria in pregnant women.
Sponsor; Funder University of Oxford; Thrasher Research Fund (with core funding by the Wellcome Trust)	Sponsor; Funder University of Oxford; Holleykin Pharmaceuticals (with core funding by the Wellcome Trust)