Revised Simplified Algorithm for Treatment Eligibility for HIV (SLATEII) (SLATEII)

Randomized Evaluation of a Revised, Simplified Clinical Algorithm for Identifying Patients Eligible for Immediate Initiation of Antiretroviral Therapy for HIV (SLATEII)

In its 2017 revision of the global guidelines for HIV care and treatment, the World Health Organization called for rapid or same-day initiation of antiretroviral treatment (ART) for eligible patients testing positive for HIV. In sub-Saharan Africa, where most HIV patients are located, studies continue to document high losses of treatment-eligible patients from care before they receive their first dose of antiretroviral medications (ARVs). Among facility-level reasons for these losses are treatment initiation protocols that require multiple clinic visits and long waiting times before a patient who tests positive for HIV is dispensed an initial supply of medications. Simpler, more efficient, accelerated algorithms for ART initiation are needed, including strategies for rapid initiation in patients with symptoms of tuberculosis, most of whom do not have active TB.

In July 2017, the original SLATE study (SLATE I) completed enrollment in South Africa. One of the most striking findings of the study so far is the large proportion of patients who "screened out" of the SLATE algorithm and were referred for additional services rather than started on ART immediately. Among 298 patients assigned to the intervention arm and evaluated for immediate treatment eligibility under the SLATE algorithm, 149 (50%) screened out, two thirds of these (100/149) due to symptoms of TB. The vast majority of the TB suspects (93/100, 93%) tested negative for active TB.

The SLATE II study will revise the original SLATE algorithm to provide a pathway for immediate ART initiation for some patients with TB symptoms. Under SLATE II, patients with TB symptoms will be clinically evaluated by the study nurse and will receive a urine point of care LAM (lipoarabinomannan antigen of mycobacteria) test. Those with milder symptoms and a negative LAM test will be offered immediate ART. Those with more serious symptoms and/or a positive LAM test will be asked to return the next day to receive TB test results and either immediate ART or TB treatment. All intervention arm patients (symptomatic and asymptomatic) will be asked for a sputum sample for Xpert testing, and positives will be contacted on the next day. The SLATE II algorithm will also incorporate other improvements identified from SLATE I.

Study Overview

• Status: Completed
• Conditions: HIV/AIDS; Antiretroviral Therapy
• Intervention / Treatment: Procedure: SLATE II

Detailed Description

SLATE II is be a pragmatic, individually randomized evaluation to determine the effectiveness of the revised algorithm in increasing ART initiation, compared to standard care, among non-pregnant adult patients. Six hundred HIV-infected adult patients not yet on ART will be enrolled during a routine clinic visit and randomized to receive the intervention or standard care. Patients in the intervention arm will be administered a revised version of the SLATE screens, including the TB add-on; those found eligible under the algorithm will be offered immediate treatment initiation, while those who are not eligible will be referred for standard clinic care. Patients in the standard arm will be referred for ART initiation under standard clinic procedures. All care after the initial visit will be by the clinic under standard care. Primary outcomes will be ART initiation within 7 days of study enrollment and viral suppression within 8 months of study enrollment.

The study is being conducted at three healthcare facilities (clinics) in South Africa. In September 2017, the South African National Department of Health instructed all clinics to offer same-day ART initiation to eligible patients but provided little guidance on determining eligibility. SLATE II will help to create such guidance. If successful, it will improve on the SLATE approach to collecting and interpreting a minimum set of patient data that will avoid delaying treatment initiation for the majority of patients who are eligible for immediate ART, while deferring initiation in the minority who should not start immediately.

• Study Type: Interventional
• Enrollment (Actual): 600
• Phase: Not Applicable

Contacts and Locations

Study Locations

• South Africa
  • Gauteng
    • Johannesburg, Gauteng, South Africa
      • Health Economics and Epidemiology Research Office

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult patients (>18 years) (initiating children and adolescents on ART is likely to require additional information and adherence support, making the SLATE algorithm less applicable to pediatric populations)
• Confirmed HIV-positive test result at any time (may have been diagnosed previously)
• Self-report that patient is not currently on ART and has not been prescribed ART in the past three months
• Presented at the study clinic for any HIV-related reason or other reason that led to referral for HIV testing or care

Exclusion Criteria:

• Pregnant (pregnancy is an exclusion criterion because treatment guidelines for pregnant women differ from those for non-pregnant adults; most pregnant women are diagnosed with HIV and initiated on ART in antenatal clinics, not general adult HIV clinics)
• Not intending to return to this clinic for further HIV care in the coming year (i.e. intends to seek further care somewhere else)
• Not willing to be traced by phone or in person for follow-up care if test results received after the enrollment visit indicate that further care is needed
• Not physically, mentally, or emotionally able to participate in the study, in the opinion of the investigators or study staff
• Not willing or able to provide written informed consent to participate in the study
• Previously enrolled in the same study or the SLATE I study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SLATE; The SLATE arm will be administered the SLATE II algorithm and initiated on ART immediately if eligible under the algorithm. Patients not eligible under the algorithm will be referred for standard care.	Procedure: SLATE II; The SLATE II algorithm is a series of questions and procedures that allow a study clinician to determine if antiretroviral therapy for HIV can be started immediately (same-day) or if additional care or services are needed before ART initiation.; Other Names: Revised Simplified Algorithm for Treatment Eligibility
No Intervention: Standard; The standard arm will be referred to standard care after study enrollment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients initiated on ART	% of enrolled patients initiated onto ART within one week of study enrollment, which may occur at HIV diagnosis or at a pre-ART follow-up visit	7 days after study enrollment
Proportion of patients initiated on ART and alive, in care, and retained	Proportion of enrolled patients initiated on ART within 28 days of study enrollment and retained in care 8 months after study enrollment, as indicated by a clinic visit no more than 7 months after ART initiation	8 months after study enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of TB suspects initiated on ART within 14 days of study enrollment	Proportion of TB suspects initiated on ART within 14 days of study enrollment	14 days after study enrollment
Proportions of patients initiated on ART within 1, 14, and 28 days of study enrollment	Proportions of patients initiated on ART within 1, 14, and 28 days of study enrollment	28 days after study enrollment
Proportions of all patients and of TB suspects who initiate ART and are virally suppressed eight months after having an HIV test or enrolling in HIV care	Viral suppression stratified by TB symptom status at baseline	8 months after study enrollment
Proportions of all patients and of TB suspects who initiate ART and are alive, in care, and retained on ART 14 months after having an HIV test or enrolling in HIV care	Retention 12 months after enrollment, allowing 1 month for initiation and 1 month for making and recording data from 12-month visit.	14 months after study enrollment
Proportions of HIV-positive patients presenting at study clinics and not yet on ART who are eligible and ineligible for immediate initiation using SLATE algorithm criteria	Patients who screen in and screen out of algorithm in intervention arm	1 day after study enrollment
Reasons for ineligibility for immediate initiation	Reasons for ineligibility for immediate initiation, among those found ineligible in the intervention arm	1 day after study enrollment
Median time to ART initiation (days) for each arm	Median and IQR time to ART initiation (days) for each arm	28 days after study enrollment
Adverse events	Frequency and types of adverse events reported in medical records after ART initiation for each follow up period	1, 7, 14, and 28 days after enrollment; 8 and 14 months after enrollment
Patient preferences	Patient self-reported preferences on the speed and timing of ART initiation, from questionnaires	1 day after enrollment
LAM test results	Proportion of symptomatic patients who test positive for TB using the LAM test	1 day after enrollment
Xpert test results	Proportions of symptomatic and asymptomatic patients who test positive for TB using Xpert MTB/RIF, among those able to produce a sputum sample	1 week after enrollment
Costs to patients	Costs to patients of ART initiation under standard and intervention procedures	14 months after study enrollment (end of followup)
Costs to providers	Costs to providers of ART initiation under standard and intervention procedures	14 months after study enrollment (end of followup)
Differences from SLATE I	Comparison of results of SLATE II study to SLATE I study	14 months after study enrollment (end of followup)

Collaborators and Investigators

• Sponsor: Boston University
• Collaborators: Bill and Melinda Gates Foundation; University of Witwatersrand, South Africa
• Investigators: Principal Investigator: Sydney B Rosen, Boston University

Publications and helpful links

General Publications

• Maskew M, Brennan AT, Venter WDF, Fox MP, Vezi L, Rosen S. Retention in care and viral suppression after same-day ART initiation: One-year outcomes of the SLATE I and II individually randomized clinical trials in South Africa. J Int AIDS Soc. 2021 Oct;24(10):e25825. doi: 10.1002/jia2.25825.
• Brennan AT, Maskew M, Larson BA, Tsikhutsu I, Bii M, Vezi L, Fox MP, Venter WD, Ehrenkranz P, Rosen S. Who is seeking antiretroviral treatment for HIV now? Characteristics of patients presenting in Kenya and South Africa in 2017-2018. J Int AIDS Soc. 2019 Sep;22(9):e25358. doi: 10.1002/jia2.25358.
• Brennan A, Maskew M, Larson BA, Tsikhutsu I, Bii M, Vezi L, Fox M, Venter WDF, Ehrenkranz PD, Rosen S. Prevalence of TB symptoms, diagnosis and treatment among people living with HIV (PLHIV) not on ART presenting at outpatient clinics in South Africa and Kenya: baseline results from a clinical trial. BMJ Open. 2020 Sep 6;10(9):e035794. doi: 10.1136/bmjopen-2019-035794.
• Scott NA, Maskew M, Fong RM, Olson IE, Brennan AT, Fox MP, Vezi L, Ehrenkranz PD, Rosen S. Patient Perspectives of Quality of the Same-Day Antiretroviral Therapy Initiation Process in Gauteng Province, South Africa: Qualitative Dominant Mixed-Methods Analysis of the SLATE II Trial. Patient. 2021 Mar;14(2):175-186. doi: 10.1007/s40271-020-00437-4.
• Rosen S, Maskew M, Brennan AT, Fox MP, Vezi L, Ehrenkranz PD, Venter WDF. Improved simplified clinical algorithm for identifying patients eligible for immediate initiation of antiretroviral therapy for HIV (SLATE II): protocol for a randomized evaluation. Trials. 2018 Oct 11;19(1):548. doi: 10.1186/s13063-018-2928-5.
• Maskew M, Brennan AT, Fox MP, Vezi L, Venter WDF, Ehrenkranz P, Rosen S. A clinical algorithm for same-day HIV treatment initiation in settings with high TB symptom prevalence in South Africa: The SLATE II individually randomized clinical trial. PLoS Med. 2020 Aug 27;17(8):e1003226. doi: 10.1371/journal.pmed.1003226. eCollection 2020 Aug.

Study record dates

Study Major Dates

• Study Start (Actual): March 14, 2018
• Primary Completion (Actual): August 19, 2019
• Study Completion (Actual): December 31, 2020

Study Registration Dates

• First Submitted: October 6, 2017
• First Submitted That Met QC Criteria: October 16, 2017
• First Posted (Actual): October 19, 2017

Study Record Updates

• Last Update Posted (Actual): January 22, 2021
• Last Update Submitted That Met QC Criteria: January 21, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: ART; Sub-Sahara Africa; Antiretroviral therapy initiation
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome
• Other Study ID Numbers: H-37010; OPP1136158 (Other Grant/Funding Number: Bill and Melinda Gates Foundation); 4852 (Registry Identifier: NHREC South Africa); 171011 (Other Identifier: HREC (Medical) Wits University)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: After protocol closure, dis-identified data generated by the study will be shared on Dryad. Data from patients' medical records do not belong to the study and cannot be shared but may be available on request from the study sites.
• IPD Sharing Time Frame: After protocol closure, which will occur approximately one year after all study outcomes have been reached.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No