Cardiac safety of dihydroartemisinin-piperaquine and sulfadoxine pyrimethamine among pregnant women with and without asymptomatic parasitaemia in Tanzania: results from an open-label, parallel-group, randomised phase II trial

Background: Dihydroartemisinin-Piperaquine (DP) can induce transient prolongation of the corrected QT interval (QTc) and is a candidate for use with sulfadoxine-pyrimethamine (SP) in intermittent preventive treatment of malaria in pregnancy (IPTp). Pregnancy can alter pharmacokinetics of antimalarial drugs. Acute malaria infection can increase QTc prolongation. Whether DP alters cardiac function in pregnant women with or without asymptomatic parasitaemia is not well characerised. Methods: This was an open-label, parallel-group, randomised phase 2 study among pregnant women in Handeni, Tanzania (NCT02909712). Women were screened for P. falciparum by microscopy and, if positive, received a rapid diagnostic test (RDT). If RDT-positive, they received DP or SP, and the next microscopy-negative woman was randomly allocated to receive DP or SP. Enrolment and allocation continued in this alternating manner to reach 200 (50/group): Grp 1 (neg; SP), Grp 2 (pos; SP), Grp 3 (neg: DP), Grp 4 (pos: DP). Standard 12-lead ECGs were used to record cardiac function in triplicate. DP groups were measured on day 0 (predose), day 2 (predose and hours 3,4,5,6,7,8), and day 7; SP groups had day 0 (predose), and day 7 ECGs. Results: DP resulted in QTcF prolongation that peaked ~30 msec at 5-h post dose 3 on day 2 (schedule: days 0,1,2). The mean maximum increase was slightly more in group 4 compared to group 3 (33.1 vs 29.1 msec). On day 7, QTcF returned to baseline in group 3; a small and non-clinically significant increase of 3.4 (90%CI: 0.3, 6.5) msec was still present among RDT-positive women. QTcB measurements were similar. There was a marked decrease in heart rate (HR) among all DP recipients on day 2, which appeared greater in group 4 compared to group 3 (13.3 vs 8.9 bpm), baseline HR was higher in group 4 than group 3 (92.7 vs 88.5 bpm). This potentially represents a regression towards the mean. On day 7, HR had returned to baseline in both groups. Conclusion: Parasite presence did not alter the effect of DP on the different ECG parameters with the possible exception of HR. No marked differences were observed between pregnant women with and without asymptomatic parasitaemia

The effect of a customised digital adherence tool on HIV treatment outcomes in young people living with HIV (YPLHIV) in Blantyre, Malawi: a protocol for a randomised controlled trial

Abstract Background People living with HIV (PLHIV) have to take lifelong antiretroviral treatment, which is often challenging. Young people living with HIV (YPLHIV) have the lowest viral load suppression rates in Malawi and globally, mostly due to poor treatment adherence. This is a result of complex interactions of multiple factors unique to this demographic group. The use of digital health interventions, such as real-time medication monitor (RTMM)-based digital adherence tools (DATs), could improve ART adherence in YPLHIV and subsequently improve viral load suppression which in turn could lead to reduced HIV-associated morbidity and mortality. Aim To provide the evidence base for a digital adherence intervention to improve treatment outcomes in YPLHIV on ART. Objectives 1. The primary objective is to determine the efficacy of a customised DAT compared to the standard of care in improving ART adherence in YPLHIV. 2. The secondary objective is to determine the efficacy of the customised DAT compared to the standard of care in improving viral load suppression in YPLHIV. Methodology This will be a parallel open-label randomised control controlled two-arm trial in which non-adherent YPLHIV in selected ART facilities in Blantyre will be randomised in a 1:1 ratio to a customised DAT and standard care arms and followed up for 9 months. The primary outcome is the proportion adherent at 9 months (> = 95% by pill count), and the secondary outcome is the proportion with viral load suppressed at 9 months (< 200 copies/ml). Discussion There is a paucity of good quality evidence on effective digital health interventions to improve ART adherence and viral load suppression in YPLHIV globally and particularly in HIV high-burden settings like Malawi. This study will provide good-quality evidence on the effectiveness of a customised DAT in improving ART adherence and viral load suppression in this important demographic. Trial registration The trial has been registered in the Pan African Clinical Trials Registry number: PACTR202303867267716 on 23 March 2023 and can be accessed through the following URL: https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=25424 . All items from the WHO Trial Registration Data Set are described in this manuscript

Effect of a customized digital adherence tool on retention in care and adherence to antiretroviral treatment in breastfeeding women, children and adolescents living with HIV in Tanzania : a mixed-methods study followed by clinical trials

Background: Adherence to antiretroviral (ARV) treatment for HIV infection is challenging because of many factors. The World Health Organization (WHO) has recommended using digital adherence technologies (DATs). However, there is limited evidence on how DATs improve adherence. Wisepill® is an internet-enabled medication dispenser found feasible and acceptable in several studies. However, limited evidence is available on its effectiveness in improving ART adherence, specifically among children and adolescents. Furthermore, DATs are often developed without involving the target groups. We propose a two-stage project consisting of a formative study to customize an existing Wisepill DAT intervention and a randomized clinical trial to investigate the effectiveness of DAT combined with reminder cues and tailored feedback on adherence to ARV treatment among children and adolescents living with HIV and retention in care among breastfeeding women living with HIV in Kilimanjaro and Arusha Region, Tanzania. Methods: We will conduct a formative mixed-methods study and three sub-trials in Kilimanjaro and Arusha Regions among (1) children aged 0–14 years and their caregivers, (2) adolescents aged 15–19 years and (3) breastfeeding women and their HIV-negative infants. In the formative study, we will collect and analyse data on needs and contents for DATs, including the contents of short message service (SMS) texts and tailored feedback. The results will inform the customization of the DAT to be tested in the sub-trials. In the trials, participants will be randomized in the intervention arm, where the DAT will be implemented or the control arm, where standard care will be followed. Participants in the intervention arm will take their medication from the Wisepill box and receive daily reminder texts and tailored feedback during clinic visits. Discussion: If the intervention improves adherence to ART and the devices are acceptable, accurate and sustainable, the intervention can be scaled up within the National Aids Control Programmes. Trial registration: PACTR202301844164954, date 27 January 2023