The "START" (a Streamlined ART Initiation Strategy) Study

Principal Investigators: Dr. Diane Havlir, UCSF and Prof Moses Kamya, Makerere University

Investigators: Elvin Geng, UCSF; Jennifer Namosobya, MJAP; Fred Semitala, MJAP; Gideon Amanyire, MJAP; James Kahn, UCSF; UCSF; Edwin Charlebois, UCSF; Maya Petersen, UCB

Coordinators: Leatitia Kampiire, IDRC and Richard Katuramu, IDRC

Location: Kampala and Mbarara, Uganda

Funded By: National Institute of Allergy and Infectious Diseases (NIAID)

ClinicalTrials.gov Identifier: NCT01810289

In the global public health response to the HIV/AIDS epidemic in Africa, optimizing the implementation of evidence-based interventions is a vital to increasing the efficiency and effectiveness of the public health response. For example, although ART for treatment-eligible HIV-infected patients reduces morbidity, mortality dramatically and mother-to-child transmission (MTCT) practically to zero, up to 20-30% of treatment eligible patients in resource limited settings fail to initiate antiretroviral therapy or encounter significant delays. Identifying a generalizable intervention that can be used to closing the gap between the known efficacy of antiretroviral therapy (ART) and the sub-optimal delivery in real world settings is the focus of this project and an example of implementation science.


We believe failures and delays in ART initiation result from four systems-based drivers in resource limited settings. First, ART eligibility is determined by CD4 testing results, but testing generally requires overnight processing and therefore results require a second visit to clinic – thus introducing the opportunity for a missed or delayed visit. Second, diffusion of knowledge from recent randomized trails that demonstrate benefit of fast ART initiation may not have reached all front line health care providers. Finally, routine requirements for multiple pre-ART adherence counseling sessions are widespread and may limit the pace and completeness of ART initiation in eligible patients.


To address these barriers, we propose a multi-component Streamlined ART Start Strategy (START) based on the "PRECEDE" health planning framework originally developed by Professor Lawrence Green, an early pioneer of implementation sciences. This model – empirically validated in diverse disease conditions– states that a combination of three factors are required for effective strategies to improve health care delivery: (1) "enabling factors" are characteristics that facilitate desired change; (2) "predisposing factors" are composed of knowledge, attitudes or beliefs that affect behavior; and (3) "reinforcing factors" are anticipated consequences following a behavior.


Our START intervention to accelerate ART initiation therefore is composed of:(1) a novel toaster-sized point of care (POC) CD4 platform (PIMA, Alere) which provides real time determination of treatment eligibility and therefore enables ART faster initiation; (2) targeted knowledge transfer to front-line providers in the form of face-to-face teaching by opinion leaders that predisposes them to timely ART initiation and (3) feedback reporting about timing of medication initiation to clinics that reinforces this approach. We will evaluate the effect of the intervention in a step-wedge cluster randomized trial with outcomes looking at ART initiation, virologic suppression and mortality. The overall goal of the START is to initiate ART among the greatest number of eligible patients in the shortest amount of time possible while maintaining safety, efficacy and cost effectiveness.
We are privileged to carry out this study partnership with Ugandan investigators and colleagues from the Makerere Joint AIDS Program which is a implementing organization funded by the US Presidents’ Emergency Fund for AIDS Relief and which delivers high quality care and treatment to over 50,000 persons living with HIV/AIDS in Uganda.


Description: http://hiv.ucsf.edu/images/start.jpg


A hypothetical kernel density histogram of the distribution of ART initiation times under standard of care and the START. In green the START setting, patients without major socio-structural barriers to ART initiation would start on the first or second visits.