Clinical trial NCT03315013: Revised Simplified Algorithm for Treatment Eligibility for HIV (SLATEII)
Official title: Randomized Evaluation of a Revised, Simplified Clinical Algorithm for Identifying Patients Eligible for Immediate Initiation of Antiretroviral Therapy for HIV (SLATEII)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV/AIDS
Antiretroviral Therapy
Keywords: Antiretroviral therapy initiation
Sub-Sahara Africa
ART
Lead sponsor: Boston University
Sponsor class: OTHER
Collaborators: name: University of Witwatersrand, South Africa
name: Bill and Melinda Gates Foundation
First posted: 2017-10-19
Enrollment: 600
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Proportion of patients initiated on ART
timeFrame: 7 days after study enrollment
measure: Proportion of patients initiated on ART and alive, in care, and retained
timeFrame: 8 months after study enrollment
Secondary outcomes:
measure: Proportion of TB suspects initiated on ART within 14 days of study enrollment
timeFrame: 14 days after study enrollment
measure: Proportions of patients initiated on ART within 1, 14, and 28 days of study enrollment
timeFrame: 28 days after study enrollment
measure: 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
timeFrame: 8 months after study enrollment
measure: 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
timeFrame: 14 months after study enrollment
measure: 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
timeFrame: 1 day after study enrollment
measure: Reasons for ineligibility for immediate initiation
timeFrame: 1 day after study enrollment
measure: Median time to ART initiation (days) for each arm
timeFrame: 28 days after study enrollment
measure: Adverse events
timeFrame: 1, 7, 14, and 28 days after enrollment; 8 and 14 months after enrollment
measure: Patient preferences
timeFrame: 1 day after enrollment
measure: LAM test results
timeFrame: 1 day after enrollment
measure: Xpert test results
timeFrame: 1 week after enrollment
measure: Costs to patients
timeFrame: 14 months after study enrollment (end of followup)
measure: Costs to providers
timeFrame: 14 months after study enrollment (end of followup)
measure: Differences from SLATE I
timeFrame: 14 months after study enrollment (end of followup)
Other outcomes:
Locations:
city: Johannesburg
country: South Africa
facility: Health Economics and Epidemiology Research Office
state: Gauteng
Study officials:
affiliation: Boston University
name: Sydney B Rosen
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.