Clinical trial NCT03242980: Short Adherence Intervention for Viral Re-suppression
Official title: Short Adherence Intervention for Viral Re-suppression (SAVIR) Study: A Stepped Wedge Randomized Controlled Study to Assess the Effect of Standardized Adherence Counselling in Individuals With Unsuppressed Viral Load in Lesotho
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Adherence, Medication
HIV/AIDS
Keywords: HIV
Adherence
Viral re-suppression
Step-wedgged randomized trial
Lead sponsor: Swiss Tropical & Public Health Institute
Sponsor class: OTHER
Collaborators: name: SolidarMed
name: Ministry of Health, Lesotho
name: University of Basel
First posted: 2017-08-08
Enrollment: 928
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: To ensure that the effect of this intervention is measured and to avoid a long delay in adopting the intervention, a stepped wedge design was chosen. In addition the study would thus not disrupt the on-going staggered roll-out of routine viral load provision to patients on ART at the 12 health facilities. Stepped wedge designs are a form of clustered study in which the intervention is delivered to groups rather than individuals.
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: In the era of test-and-treat, with anticipated high numbers of patients who will have unsuppressed viral load (VL) due to poor adherence, simple, short and standardized adherence interventions with documented efficacy will be needed. Achieving re-suppression in patients with unsuppressed VL is beneficial for the health of the individual, important to reduce the risk of transmission and has a direct cost implication because patients with sustained unsuppressed VL will ultimately be switched to more expensive 2nd-line regimens.

Information is still largely lacking on how to best address adherence problems among patients with unsuppressed VL. VL monitoring is recognized as a useful tool to reinforce adherence in patients with unsuppressed VL. The Lesotho Guidelines recommend redoing a VL 8-12 weeks after the first enhanced adherence counselling. To date no study has been published clearly demonstrating higher re-suppression rates after enhanced adherence counselling for patients with unsuppressed VL.

This project aims to test an adherence intervention for HIV-positive individuals on first-line ART who have an unsuppressed viral load. A step wedged study will be used to compare the effectiveness of a short, standardized adherence counselling followed by an SMS reminder to the standard of care (≥ 2 unstructured adherence counselling sessions) in terms of viral re-suppression rates and switches to 2nd line ART.

Detailed description: Due to a lack of routine viral load (VL) monitoring in Lesotho until now, most health care workers in the districts lack the necessary information on how to manage patients with elevated viral loads. The CART-1 study found re-suppression rates of only 30% with only 70% returning for a second VL. From these estimates, it is clear that the current practice for managing these patients must be improved. A simple intervention has been designed that could be feasibly adapted at all health centres in Lesotho.

To ensure that the effect of this intervention is measured and to avoid a long delay in adopting the intervention, a stepped wedge design was chosen. In addition the study would thus not disrupt the on-going staggered roll-out of routine viral load provision to patients on ART at the 12 health facilities. Stepped wedge designs are a form of clustered study in which the intervention is delivered to groups rather than individuals. In this case, the cluster is the hospital or health centre. Each health centre will undergo a time period with the standard of care and then will be randomly selected to cross-over to the intervention at different time points, until all of the health centres have crossed-over to receive the intervention. Data on the endpoint will be collected continuously at all health centres. The use of a step wedged study is pragmatic - the intervention is offered to exert its expected benefits and research insight is a secondary aim. This innovative design will lead to much stronger evidence than observational studies.

Routine VL (viral load) monitoring started in Butha-Buthe hospital in December 2015, in Seboche Hospital in May 2016 and the remaining 10 health centres in June 2016. Once each hospital/health center has implemented routine VL monitoring for a least 12 weeks, the standardized adherence intervention will be rolled out to the hospitals/health centers in a randomized fashion. Every 12 weeks starting in May 2017, two hospitals/health centers will be randomly selected to start with the adherence intervention.

Randomization times will be separated by 12 weeks to allow for implementation and assessment of the intervention within each time period. Final data collection will occur in October 2018. All nurses at the centres will be trained in the standardized adherence counselling by an experienced professional counselor and an experienced ART nurse prior to the introduction of the intervention.

The tracing of patients who do not show up for adherence counselling sessions or confirmatory VL will be done according to the current system in use at the health centre (usually contact individual via village health worker or phone if available) and will remain the same during both the control and intervention period.

Eligibility criteria: Inclusion Criteria:

* All patients receiving VL monitoring at one of the 2 hospitals and 10 health centres in Butha-Buthe district
* Patients on first-line ART
* Patients with a VL≥ 1000 copies/mL after a minimum of 6 months on first-line ART

Exclusion Criteria:

* Patients receiving VL monitoring at a non-participating center in Butha-Buthe

Primary outcomes:
measure: Re-suppression rates after one elevated viral load
timeFrame: Up to 16 weeks
Secondary outcomes:
measure: Rates of switch to second-line ART
timeFrame: Up to 6 months
measure: Major drug resistance mutations
timeFrame: 3 months after 1st elevated VL
measure: Rates of attrition from care
timeFrame: 6 months
measure: Rates of viral re-suppression
timeFrame: 6 months after switch
Other outcomes:
Locations:
city: Butha-Buthe
country: Lesotho
facility: Boiketsiso Health Center
city: Butha-Buthe
country: Lesotho
facility: Linakeng Health Center
city: Butha-Buthe
country: Lesotho
facility: Makhunoane Health Center
city: Butha-Buthe
country: Lesotho
facility: Motete Health Center
city: Butha-Buthe
country: Lesotho
facility: Muela Health Center
city: Butha-Buthe
country: Lesotho
facility: Ngoajane Health Center
city: Butha-Buthe
country: Lesotho
facility: Paballong
city: Butha-Buthe
country: Lesotho
facility: Rampai Health Center
city: Butha-Buthe
country: Lesotho
facility: Seboche
city: Butha-Buthe
country: Lesotho
facility: St Paul Health Center
city: Butha-Buthe
country: Lesotho
facility: St Peters Health Center
city: Butha-Buthe
country: Lesotho
facility: Tsime Health Center
Study officials:
affiliation: Swiss TPH
name: Tracy R Glass, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Swiss TPH
name: Niklaus Labhardt, MD
role: STUDY_CHAIR
References:
citation: Government of Lesotho: NATIONAL GUIDELINES ON THE USE OF ANTIRETROVIRAL THERAPY FOR HIV PREVENTION AND TREATMENT. Fifth Edition 2016.
citation: Conway B. The role of adherence to antiretroviral therapy in the management of HIV infection. J Acquir Immune Defic Syndr. 2007 Jun 1;45 Suppl 1:S14-8. doi: 10.1097/QAI.0b013e3180600766.
citation: Bonner K, Mezochow A, Roberts T, Ford N, Cohn J. Viral load monitoring as a tool to reinforce adherence: a systematic review. J Acquir Immune Defic Syndr. 2013 Sep 1;64(1):74-8. doi: 10.1097/QAI.0b013e31829f05ac.
citation: Jobanputra K, Parker LA, Azih C, Okello V, Maphalala G, Kershberger B, Khogali M, Lujan J, Antierens A, Teck R, Ellman T, Kosgei R, Reid T. Factors associated with virological failure and suppression after enhanced adherence counselling, in children, adolescents and adults on antiretroviral therapy for HIV in Swaziland. PLoS One. 2015 Feb 19;10(2):e0116144. doi: 10.1371/journal.pone.0116144. eCollection 2015.
citation: Ministry of Health and Social Welfare Lesotho: National Guidelines For HIV Testing And Counselling. National Guidelines For HIV Testing And Counselling 2009.