MaxART: Early Access to ART for All in Swaziland (MaxART)

The purpose of this study is to evaluate the feasibility, acceptability, clinical outcomes, affordability, and scalability of offering early antiretroviral treatment to all HIV-positive individuals in Swaziland's government-managed health system.

Study Overview

• Status: Completed
• Conditions: HIV/AIDS
• Intervention / Treatment: Other: Early Access to ART for All

Detailed Description

The clinical evidence in support of offering antiretroviral treatment (ART) for all HIV-positive individuals to improve patient health outcomes and reduce HIV incidence is building, and the resource-limited countries where this approach could have the biggest impact want to evaluate if this is a feasible and effective intervention to turn the course of their HIV epidemics. The MaxART Early Access to ART for All (EAAA) implementation study was designed to determine the feasibility, acceptability, clinical outcomes, affordability, and scalability of offering early antiretroviral treatment to all HIV-positive individuals in Swaziland's government-managed health system.

This is a 3-year randomized stepped wedge design with open enrollment for all adults 18 years and older across 14 rural health facilities in Swaziland's Hhohho Region. Primary endpoints are retention and viral suppression. Secondary endpoints include ART initiation, adherence, drug resistance, tuberculosis, HIV disease progression, and cost per patient per year.

Sites are grouped to transition two at a time from the control (standard of care) to intervention (EAAA) stage at each 4-month step. This balanced design will result in approximately one half of the observations being under an intervention clinic, and the other half under control.

Power calculations were conservatively based on the estimated number of individuals expected to enroll in the study comparing the first 12-month measure of retention and 6-month of viral suppression on ART of those entering clinics during their control stage versus those that will be entering a clinic during intervention period.

A strategic mix of multidisciplinary research methodologies will be applied to meet the study aim, including implementation science, social science research, economic evaluations, and HIV incidence modeling.

• Study Type: Interventional
• Enrollment (Actual): 3485
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Swaziland
  • Mbabane, Swaziland
    • Swaziland Ministry of Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• All ART-naive HIV-positive individuals who are 18 years of age or older - excluding pregnant or breastfeeding women - who attend the health facilities included in the study will be asked for their consent to enroll in the study.

Exclusion Criteria:

• All HIV-positive individuals who < 18 years of age or older and pregnant or breastfeeding women.
• All HIV-positive individuals who did not consent to participate or who have already been initiated on ART.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: National HIV Treatment Guidelines; HIV-positive individuals are offered ART per Swaziland's national treatment guidelines
Experimental: Early Access to ART for All; HIV-positive individuals are initiated on ART regardless of client's immunological and clinical staging	Other: Early Access to ART for All; All HIV-positive individuals will be initiated on Swaziland's recommended first-line ART regimen, unless contraindicated when recommended alternate regimens will be used per national guidelines.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Retention	Proportion of individuals retained in care or on ART at 12 months	12 months
Viral suppression	Proportion of individuals whose viral load is below 1,000 copies/ml (virally suppressed) after 6 months on ART	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
12-month mortality rate	mortality rate among clients newly enrolled in or returning to facilities during the standard of care phase is equal to 12-month mortality rate among clients newly enrolled in or returning to facilities during early ART phase	12 months
Visit adherence among those initiated on ART	Proportion of missed visits as a number of scheduled appointments among ART-ineligible clients by end of follow-up	36 months
Drug resistance	Proportion of drug resistance among ART-ineligible clients with two virological failures who have received genotype resistance testing	36 months
Tuberculosis	Proportion of HIV-positive individuals diagnosed with new tuberculosis following enrollment (recurrent and newly incident).	36 months
ART uptake among those who are eligible	Proportion of HIV-positive individuals who are eligible for initiation who are successfully initiated to ART within 1 and 3 months of becoming eligible	3 months
Cost per patient per year	Bottom-up and top-town costing of the patient lifetime cost to test, treat, link, and retain individuals on ART	12 months
HIV infection	Mathematical modeling to estimate the number of new adult HIV infections using empirical data from the primary endpoints	36 months

Collaborators and Investigators

• Sponsor: Clinton Health Access Initiative Inc.
• Collaborators: University of Amsterdam; Harvard School of Public Health (HSPH); Ministry of Health, Swaziland; STOP AIDS NOW! (SAN!); Swaziland National Network of People Living with HIV/AIDS (SWANNEPHA); Southern African AIDS Information Dissemination Service (SAfAIDS); Southern African Centre for Epidemiological Modelling and Analyses (SACEMA)
• Investigators: Principal Investigator: Velephi Okello, MD, Ministry of Health, Swaziland

Publications and helpful links

General Publications

• Briggs J, Teyssier N, Nankabirwa JI, Rek J, Jagannathan P, Arinaitwe E, Bousema T, Drakeley C, Murray M, Crawford E, Hathaway N, Staedke SG, Smith D, Rosenthal PJ, Kamya M, Dorsey G, Rodriguez-Barraquer I, Greenhouse B. Sex-based differences in clearance of chronic Plasmodium falciparum infection. Elife. 2020 Oct 27;9:e59872. doi: 10.7554/eLife.59872.
• Steinert JI, Khan S, Mlambo K, Walsh FJ, Mafara E, Lejeune C, Wong C, Hettema A, Ogbuoji O, Vollmer S, De Neve JW, Mazibuko S, Okello V, Barnighausen T, Geldsetzer P. A stepped-wedge randomised trial on the impact of early ART initiation on HIV-patients' economic outcomes in Eswatini. Elife. 2020 Aug 24;9:e58487. doi: 10.7554/eLife.58487.
• Mobegi FM, Leong LE, Thompson F, Taylor SM, Harriss LR, Choo JM, Taylor SL, Wesselingh SL, McDermott R, Ivey KL, Rogers GB. Intestinal microbiology shapes population health impacts of diet and lifestyle risk exposures in Torres Strait Islander communities. Elife. 2020 Oct 19;9:e58407. doi: 10.7554/eLife.58407.
• Walsh FJ, Barnighausen T, Delva W, Fleming Y, Khumalo G, Lejeune CL, Mazibuko S, Mlambo CK, Reis R, Spiegelman D, Zwane M, Okello V. Impact of early initiation versus national standard of care of antiretroviral therapy in Swaziland's public sector health system: study protocol for a stepped-wedge randomized trial. Trials. 2017 Aug 18;18(1):383. doi: 10.1186/s13063-017-2128-8.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2014
• Primary Completion (Actual): August 31, 2017
• Study Completion (Actual): August 31, 2017

Study Registration Dates

• First Submitted: July 10, 2016
• First Submitted That Met QC Criteria: September 18, 2016
• First Posted (Estimate): September 21, 2016

Study Record Updates

• Last Update Posted (Actual): July 18, 2018
• Last Update Submitted That Met QC Criteria: July 17, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: HIV/AIDS, Swaziland
• 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: MaxART

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO