Current Organisation

 Desmond Tutu Health Foundation and University of Cape Town

Current Job Title

Centre for Adherence and Therapeutics, Clinical Research Site Leader

Biography

Publications

Project Title

Improving RETention and viral load outcomes for people taking Antiretroviral therapy through early IdentificatioN of missed doses [The RETAIn study].

EDCTP Project Call

Senior Fellowship Plus (SFP)

Host Organisation

Project Objectives

The SFP2812 grant contains several objectives: related to the two nested research studies (SUSTAIN and RETAIN), and those of equal importance from other work packages, such as development of the senior fellow’s mentorship skills, delivery of the trainee fellow’s research study and building of research capacity in an African setting. Research Study Objectives: The main objective of the RETAIN study is to investigate the immediate effects of an adherence intervention on individual adherence behaviours. This is done by monitoring changes in daily medication dosing and drug concentrations – for both short and long half-life drugs – right before and shortly after the intervention (using intra-individual analyses). We also assess the immediate effects on viral load. For the SUSTAIN study, the primary outcome is to compare the proportion of individuals achieving viral suppresion after 24 months between different study groups. In addition, we will evaluate retention of care (evidence of clinic attendance) and the presence of HIV-drug resistance – especially focusing on dolutegravir – in those experiencing viral failure. In the RETAIN study, the primary outcomes include changes in 30-day daily dosing (using Wisepill®) and drug concentrations i.e., plasma tenofovir levels, tenofovir diphosphate from dried blood spot samples, and urine tenofovir through a new lateral flow assay) immediately before and within four weeks after the adherence intervention. Lastly, we will also examine the intervention’s impact on viral load, retention in care, and viral suppression rates at 12 months.

Study Design

Interventional

Project Summary

Too few South Africans living with HIV achieve viral suppression. Although advances in antiretroviral therapy (ART) have reduced illness and death for people with HIV (PWH), ongoing evidence highlights gaps in the HIV continuum, including poor tablet taking / adherence and low retention in care, particularly early after ART is started in resource-poor, high-burden African settings. Those who miss doses are often later lost to care. We need to address two critical priorities: first, PWH at risk of treatment failure must be identified more rapidly than current systems allow, before they leave care or develop drug resistance; second, these patients need support to keep them in care at optimal adherence levels. Through this grant we address both problems by the synergy of two projects: a highly efficient, locally informed randomised study for which the Senior Fellow was funded through an NIH R01 mechanism, called SUSTAIN, together with this EDCTP-funded project (RETAIN). Both are being conducted at three clinics in two resource-poor communities in Cape Town, South Africa (Gugulethu and Philippi). The parent SUSTAIN study evaluates two improved, but feasible, methods of flagging and contacting those people with poor adherence earlier than the current standard of care (raised viral load); namely 1. missed clinical visits / medication pick-ups, and 2. real-time electronic monitoring of adherence with the Wisepill RT2000 device (www.wisepill.com). Standard of care (SOC) would flag poor adherence based on a raised viral load (VL) twice in the first year; missed clinic visits or medication pickup gives the opportunity to flag poor adherence up to 8 times in the first year; and missing doses noted by the Wisepill device can flag poor adherence every week of the first year on ART. The RETAIN study adds an intensive therapeutic monitoring component to all those flagged with adherence lapses to clearly describe the viral load status and drug concentrations in those struggling to adhere, and to show the immediate benefit of the adherence intervention. Both studies will contribute to the implementation of an enhanced version of the packaged adherence intervention already in place in antiretroviral clinics. The study team aims to review the impact of this earlier flagging and adherence intervention both on immediate adherence behaviour and drug concentrations (short and long half-life moieties) (RETAIN); as well as on the longer-term outcome of viral suppression at 12 months (RETAIN) and 24 months (SUSTAIN). In addition, through the mentorship component of this Fellowship, a Nigerian Trainee Fellow has designed a pilot study to explore whether a medication adherence app (Lu Dedoo) can improve ART retention and adherence in newly diagnosed adolescents living with HIV in Benue state, Nigeria. Both projects support health and well-being for all at all ages, compatible with SDG3. In the first three years of the grant, both studies received appropriate local approvals and have completed recruitment. RETAIN has recruited 100% (180/180) of participants to date, and all have completed the study. Lu Dedoo has completed the qualitative component and enrolled all 60 young people to the randomised study. RETAIN data is being cleaned for final analysis. An abstract will be prepared for the 13th IAS Conference on HIV science in Kigali in 2025. We anticipate that a primary manuscript will be complete at a similar time. Through the collaboration and teamwork engendered by this Fellowship, the careers of four African researchers are being promoted and enhanced: the Senior Fellow and the Trainee Fellow (ongoing from 2021-2025), a PhD student (2023-2025) and a Master's student, due to graduate this year, thus increasing research capacity in Africa. Both PhD and MSc students have presented related abstracts and posters at local and international conferences.

Project Title

 A randomised controlled trial of real-time electronic adherence monitoring with text message dosing reminders in people starting first-line antiretroviral therapy

EDCTP Project Call

Senior Fellowship (SF)

Host Organisation

Project Objectives

This study will use a locally developed real time adherence monitoring tool to explore and improve adherence in ART-naïve individuals commencing treatment in an established ART cohort. The study will use adherence, virological and pharmacokinetic data to examine adherence failure discordance. The questions to be answered by the study are: 1. Does a real-time electronic adherence monitoring tool with text message feedback improve adherence, retention in care and virological outcomes among ART-naïve individuals receiving first-line therapy? 2. Does population pharmacokinetic data explain discordance between adherence and virological response?

Study Design

A randomised controlled trial with two arms, as follows: Control arm: Standard of care at ART clinic with use of an electronic adherence monitoring device (EAMD or Wisepill) to monitor adherence only (i.e., without any feedback). Experimental group: Control arm with the addition of the use of the EAMD text message service when dosing late, and EAMD dosing feedback at 4-monthly visits.

Results & Outcomes