Revised Simplified Algorithm for Treatment Eligibility for HIV (SLATEII)

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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HIV/AIDS, Antiretroviral Therapy

Intervention / Treatment
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* Procedure: SLATE II


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SLATE<br>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<br>* 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.<br>* Other names: Revised Simplified Algorithm for Treatment Eligibility;|
| No Intervention: Standard<br>The standard arm will be referred to standard care after study enrollment. | |

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ART, Antiretroviral therapy initiation, Sub-Sahara Africa