HIV Treatment Retention Interventions for Women Living With HIV (Siyaphambili Study)

Study Overview
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Brief Summary
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The Siyaphambili Study is a sequential multistage adaptive randomized trial (SMART) to compare the effectiveness and durability of two behavioral interventions on the HIV-1 virologic response among female sex workers (FSW) living with HIV in Durban, South Africa. The interventions are: 1) nurse-led decentralized treatment program (DTP) and 2) individualized case management (ICM). Viral suppression is defined as a viral load assessment <50 RNA copies/mL. The design will also estimate the incremental cost-effectiveness of study interventions and combinations of interventions compared with maintaining the South African standard of HIV care and treatment.

Detailed Description
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RATIONALE: Approximately 60% of the estimated 121,000 - 167,000 female sex workers (FSW) in South Africa are living with HIV. Research suggests only 39% of these women are currently on antiretroviral therapy (ART) and face individual, network and structural level barriers to ART initiation, retention and adherence. To prevent clinical treatment outcome disparities and reduce onward HIV transmission, understanding how best to adapt and implement, scalable and effective interventions to promote viral suppression among marginalized women is paramount. The overall goal of the Siyaphambili study is to inform South African HIV service delivery and scale up determining the most cost-effective package needed to achieve viral suppression among FSW and by characterizing the FSW most in need of these intensive HIV treatment interventions. HYPOTHESIS: DTP and ICM will be equally effective at achieving viral suppression and will have a synergistic effect when combined and targeted at those who remain non-responsive to either isolated intervention. Additionally, an adaptive, graduated multicomponent intervention to achieve viral suppression would be preferred under standard thresholds for cost-effectiveness over single-intensity interventions or intensive multicomponent interventions for all FSW. INTERVENTION: The Siyaphambili Study is a sequential multistage adaptive randomized trial (SMART) to compare the effectiveness and durability of two behavioral interventions on the HIV-1 virologic response among FSW living with HIV in Durban, South Africa. The interventions are: 1) nurse-led decentralized treatment program (DTP) and 2) individualized case management (ICM). The design will also estimate the incremental cost-effectiveness of study interventions and combinations of interventions compared with maintaining the South African standard of HIV care and treatment. STUDY DESIGN: A sequential multistage adaptive randomized study, embedded within the TB/HIV Care program in Durban, South Africa, will enroll 800 viremic FSW into the 18-month trial. Women will be randomized to either DTP or ICM at enrolment and rerandomized 6 months after enrolment based on their response to the initial intervention. PRIMARY OBJECTIVE: To compare the effectiveness and durability of nurse-led DTP and ICM in isolation or in combination to achieve viral suppression. SECONDARY OBJECTIVE: To estimate the incremental impact and cost-effectiveness associated with study interventions and combination of interventions. OUTCOMES: The primary outcome of the study is retention and viral suppression among those initially randomized to the DTP verse ICM intervention. The secondary outcomes are retention and viral suppression of non-responders, retention and viral suppression among month 6 non-responders, retention and viral suppression at 18 months among month 6 non-responders randomized to continuation of either intervention verse combined DTP+ICM, risk stratification tool, durability of retention and viral suppression of responders, to assess adherence, to assess viral suppression of retained, loss-to-follow-up, intervention acceptability, switching to 2nd/3rd line ART, and ART resistance. ANALYTIC PLAN: Primary analysis for primary outcome: Retention in ART care and viral suppression will be a combined outcome in an intention to treat (ITT) analysis at 18 months to compare participants initially randomized to the DTP verse ICM intervention. Viral suppression is defined as a viral load assessment <50 RNA copies/mL and participants lost to follow up or who experience death during the trial duration will be grouped with non-virally suppressed participants.

Official Title
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An Adaptive Randomized Evaluation of Nurse-Led HIV Treatment Retention Interventions for Women Living With HIV in Durban, South Africa

Conditions
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HIV-1 Virologic Response

Intervention / Treatment
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* Behavioral: DTP
* Behavioral: ICM


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Sells sex for goods or money as their main source of income Assigned female sex at birth ≥ 18 years of age Living with HIV; diagnosed ≥ 6 months prior Currently living in Durban If on ART, initiated ≥2 months prior Exclusion Criteria: Engagement in an ongoing HIV treatment research study Planning on leaving Durban for more than 3 months in the following 12 months Pregnant at time of enrollment On a second line or third ART regimen Participating in an adherence club

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: This sequential multistage adaptive randomized trial (SMART) assesses two interventions to address treatment barriers: (1) nurse-led mobile decentralized treatment programs (DTP) and (2) peer-led, individualized case management (ICM).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: DTP, Continue DTP if Responsive<br>DTP: Standard of care (SoC), minus clinic referrals for antiretroviral therapy (ART) treatment initiation and management. Nurse initiated and managed ART within the community on mobile van at sites served by the mobile van which already provides SoC services Continues with DTP intervention if virally suppressed at 6 months. | Behavioral: DTP<br>* Provision of antiretroviral therapy (ART) in the community through a mobile-van DTP managed by a nurse capable of initiating and managing ART.<br>|
| Active Comparator: DTP, Standard of Care (SoC) if Responsive<br>DTP: Standard of care, minus clinic referrals for ART treatment initiation and management. Nurse initiated and managed ART within the community on mobile van at sites served by the mobile van which already provides SoC services SoC: HIV counseling and testing (HTC) Sexually transmitted infection (STI) screening and treatment Tuberculosis (TB) screening and referral Health education through peer educators and peer supported follow-up related to linkages to care Referrals to Department of Health (DoH) primary healthcare clinics or TB HIV Care (THC) drop-in center for ART treatment initiation and management Returns to SoC if virally suppressed at 6 months. | Behavioral: DTP<br>* Provision of antiretroviral therapy (ART) in the community through a mobile-van DTP managed by a nurse capable of initiating and managing ART.<br>|
| Active Comparator: DTP, Continue DTP if Non-Responsive<br>DTP: Standard of care, minus clinic referrals for ART treatment initiation and management. Nurse initiated and managed ART within the community on mobile van at sites served by the mobile van which already provides SoC services Continues with DTP intervention if not virally suppressed at 6 months. | Behavioral: DTP<br>* Provision of antiretroviral therapy (ART) in the community through a mobile-van DTP managed by a nurse capable of initiating and managing ART.<br>|
| Active Comparator: DTP, DTP+ICM if Non-Responsive<br>DTP: Standard of care, minus clinic referrals for ART treatment initiation and management. Nurse initiated and managed ART within the community on mobile van at sites served by the mobile van which already provides SoC services ICM: Standard of Care Assignment of peer case manager Face-to-face meeting to tailor ICM approach to FSW preference Self-efficacy building in face-to-face sessions and bi-weekly text messages Relational support through monthly calls, face-to-face meetings every three months, and additional support through female sex worker (FSW) initiated interaction Receives both interventions at 6 months if non-virally suppressed. | Behavioral: DTP<br>* Provision of antiretroviral therapy (ART) in the community through a mobile-van DTP managed by a nurse capable of initiating and managing ART.<br>Behavioral: ICM<br>* Peer-led ICM through quarterly face-to-face meetings, monthly phone calls and biweekly text messages.<br>|
| Active Comparator: ICM, Continue ICM if Responsive<br>ICM: Standard of Care Assignment of peer case manager Face-to-face meeting to tailor ICM approach to FSW preference Self-efficacy building in face-to-face sessions and bi-weekly text messages Relational support through monthly calls, face-to-face meetings every three months, and additional support through FSW initiated interaction Continues with ICM intervention at 6 months if virally suppressed. | Behavioral: ICM<br>* Peer-led ICM through quarterly face-to-face meetings, monthly phone calls and biweekly text messages.<br>|
| Active Comparator: ICM, SoC if Responsive<br>ICM: Standard of Care Assignment of peer case manager Face-to-face meeting to tailor ICM approach to FSW preference Self-efficacy building in face-to-face sessions and bi-weekly text messages Relational support through monthly calls, face-to-face meetings every three months, and additional support through FSW initiated interaction SoC: HIV counseling and testing (HTC) STI screening and treatment TB screening and referral Health education through peer educators and peer supported follow-up related to linkages to care Referrals to DOH primary healthcare clinics or THC drop-in center for ART treatment initiation and management Returns to SoC if virally suppressed at 6 months. | Behavioral: ICM<br>* Peer-led ICM through quarterly face-to-face meetings, monthly phone calls and biweekly text messages.<br>|
| Active Comparator: ICM, Continue ICM if Non-Responsive<br>ICM: Standard of Care Assignment of peer case manager Face-to-face meeting to tailor ICM approach to FSW preference Self-efficacy building in face-to-face sessions and bi-weekly text messages Relational support through monthly calls, face-to-face meetings every three months, and additional support through FSW initiated interaction Continues with ICM intervention at 6 months if non-virally suppressed. | Behavioral: ICM<br>* Peer-led ICM through quarterly face-to-face meetings, monthly phone calls and biweekly text messages.<br>|
| Active Comparator: ICM, ICM+DTP if Non-Responsive<br>ICM: Standard of Care Assignment of peer case manager Face-to-face meeting to tailor ICM approach to FSW preference Self-efficacy building in face-to-face sessions and bi-weekly text messages Relational support through monthly calls, face-to-face meetings every three months, and additional support through FSW initiated interaction DTP: Standard of care, minus clinic referrals for ART treatment initiation and management. Nurse initiated and managed ART within the community on mobile van at sites served by the mobile van which already provides SoC services Receives both interventions at 6 months if non-virally suppressed. | Behavioral: DTP<br>* Provision of antiretroviral therapy (ART) in the community through a mobile-van DTP managed by a nurse capable of initiating and managing ART.<br>Behavioral: ICM<br>* Peer-led ICM through quarterly face-to-face meetings, monthly phone calls and biweekly text messages.<br>|
| No Intervention: Standard of Care (SoC)<br>Standard of Care (SoC): HIV counseling and testing (HTC) Sexually transmitted infection (STI) screening and treatment Tuberculosis (TB) screening and referral Health education through peer educators and peer supported follow-up related to linkages to care Referrals to Department of Health (DoH) primary healthcare clinics or TB HIV Care (THC) drop-in center for ART treatment initiation and management | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Retained and Virally Suppressed Among Those Receiving the DTP Versus ICM Arms | Retention and viral suppression at 18 months in those initially randomized to DTP vs. ICM. Participants are considered to be retained in care if they attended their 18-month final study visit and were engaged in care at 18-months. Viral suppression is defined as having less than 50 viral copies per milliliter. | 18 months after enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Retention and Viral Suppression of Non-Responders | Retention and viral suppression at 18 months among month 6 non-responders randomized to continuation of either intervention vs. combined DTP+ICM | 18 months after enrollment | 
| Risk Factors of Loss to Follow-up | Risk stratification to identify FSW at highest risk for loss to follow-up. | Up to 18 months after enrollment | 
| Durability of Retention and Viral Suppression of Responders | Durability of retention and viral suppression among 6 month responders continuing on DTP or ICM vs. those randomized to revert to standard of care (SoC) | Up to 18 months after enrollment | 
| Adherence Assessment | Self-reported adherence to assess adherence across arms | 18 months | 
| Viral Suppression of Retained | Among those retained, comparison of viral suppression across arms | Up to 18 months after enrollment | 
| Loss-to-Follow-Up | Loss-to-follow-up across arms (DTP vs. ICM). This outcome is presented as an intention to treat analysis based on baseline randomization (DTP vs. ICM). All 777 participants randomized at baseline are included here. Loss to follow-up is defined as having missed the 18-month final study visit. | 18 months after study enrollment | 
| Intervention Acceptability | Participant reported intervention acceptability | Acceptability of each intervention at 6 month timepoint | 
| 2nd/3rd Line ART | Number of participants who were tested and identified as resistant to first line therapy and were referred to a Department of Health facility for second line therapy across arms | Up to 18 months after enrollment | 
| ART Resistance | Report and compare resistance across arms | Up to 18 months after enrollment | 
| Comparative Cost-effectiveness of Intervention | This outcome will be estimated using a modeling approach leveraging both the trial data and external evidence synthesis as model inputs. Passive data collection is ongoing and cost-effectiveness results will be reported once available (by March 2024). | Up to 18 months after enrollment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, Female Sex Workers, Viral Suppression, South Africa, Decentralized care, Antiretroviral therapy, Differentiated care