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

• ClinicalTrials.gov Identifier: NCT03500172
• Recruitment Status: Completed
• First Posted: April 17, 2018
• Last Update Posted: November 23, 2022
• Sponsor: Johns Hopkins Bloomberg School of Public Health
• Collaborators: University of the Western Cape; TB/HIV Care; University of Toronto; University of California, San Francisco; National Institute for Communicable Diseases, South Africa
• Information provided by (Responsible Party): Johns Hopkins Bloomberg School of Public Health

Tracking Information

• First Submitted Date: April 9, 2018
• First Posted Date: April 17, 2018
• Last Update Posted Date: November 23, 2022
• Actual Study Start Date: June 22, 2018
• Actual Primary Completion Date: November 24, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 9, 2018)

Retention and Viral Suppression of DTP verse ICM [ Time Frame: 18 months after enrollment ]

Retention and viral suppression at 18 months in those initially randomized to DTP vs. ICM

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 9, 2018)

• Retention and Viral Suppression of Non-Responders [ Time Frame: 18 months after enrollment ]
  Retention and viral suppression at 18 months among month 6 non-responders randomized to continuation of either intervention vs. combined DTP+ICM
• Risk factors of uncontrolled viremia and/or lost to follow-up [ Time Frame: Up to 18 months after enrollment ]
  Risk stratification tool to identify FSW at highest risk for uncontrolled viremia and/or lost to follow-up.
• Durability of Retention and Viral Suppression of Responders [ Time Frame: Up to 18 months after enrollment ]
  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)
• Adherence Assessment [ Time Frame: 6, 12 and 18 months ]
  Self-reported adherence and refill pick-up data to assess adherence across arms
• Viral Suppression of Retained [ Time Frame: Up to 18 months after enrollment ]
  Among those retained, comparison of viral suppression across arms
• Loss-to-Follow-Up [ Time Frame: 18 months after study enrollment ]
  Loss-to-follow-up across arms
• Intervention Acceptability [ Time Frame: Up to 18 months after enrollment ]
  Participant reported intervention acceptability
• 2nd/3rd Line ART [ Time Frame: Up to 18 months after enrollment ]
  Numbers switching to 2nd/3rd Line ART across arms
• ART Resistance [ Time Frame: Up to 18 months after enrollment ]
  Report and compare resistance across arms
• Comparative cost-effectiveness of intervention [ Time Frame: Up to 18 months after enrollment ]
  Comparison of intervention cost-effectiveness according to order of intervention and duration of intervention received

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: April 9, 2018)

• DTP Pick-Ups [ Time Frame: Up to 18 months after enrollment ]
  Number and proportion of DTP pick-ups attended within 7-days of scheduled visit
• ICM Phone-Based Contacts [ Time Frame: Up to 18 months after enrollment ]
  Number of ICM phone-based contacts; proportion of participant initiating phone-based contacts at 6, 12 and 18 months
• ICM In-Person Meetings [ Time Frame: Up to 18 months after enrollment ]
  Proportion of face-to-face case manager sessions attended

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: HIV Treatment Retention Interventions for Women Living With HIV (Siyaphambili Study)
• Official Title: An Adaptive Randomized Evaluation of Nurse-Led HIV Treatment Retention Interventions for Women Living With HIV in Durban, South Africa
• Brief Summary: 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

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.

• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention 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)
Primary Purpose: Treatment

• Condition: HIV-1 Virologic Response

Intervention

• Behavioral: DTP
  Provision of antiretroviral therapy (ART) in the community through a mobile-van DTP managed by a nurse capable of initiating and managing ART.
• Behavioral: ICM
  Peer-led ICM through quarterly face-to-face meetings, monthly phone calls and biweekly text messages.

Study Arms

• Active Comparator: DTP, Continue DTP if Responsive

  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 virally suppressed at 6 months.

  Intervention: Behavioral: DTP
• Active Comparator: DTP, Standard of Care (SoC) if Responsive

  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)
  • 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.

  Intervention: Behavioral: DTP
• Active Comparator: DTP, Continue DTP if Non-Responsive

  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.

  Intervention: Behavioral: DTP
• Active Comparator: DTP, DTP+ICM if Non-Responsive

  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.

  Interventions:

  • Behavioral: DTP
  • Behavioral: ICM
• Active Comparator: ICM, Continue ICM if Responsive

  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.

  Intervention: Behavioral: ICM
• Active Comparator: ICM, SoC if Responsive

  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.

  Intervention: Behavioral: ICM
• Active Comparator: ICM, Continue ICM if Non-Responsive

  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.

  Intervention: Behavioral: ICM
• Active Comparator: ICM, ICM+DTP if Non-Responsive

  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.

  Interventions:

  • Behavioral: DTP
  • Behavioral: ICM

• Publications *: Wang L, Dowdy DW, Comins CA, Young K, Mcingana M, Mulumba N, Mhlophe H, Chen C, Hausler H, Schwartz SR, Baral S, Mishra S; Siyaphambili Study team. Health-related quality of life of female sex workers living with HIV in South Africa: a cross-sectional study. J Int AIDS Soc. 2022 Feb;25(2):e25884. doi: 10.1002/jia2.25884.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 31, 2020): 1391
• Original Estimated Enrollment (submitted: April 9, 2018): 1143
• Actual Study Completion Date: January 5, 2022
• Actual Primary Completion Date: November 24, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Sells sex for goods or money as their main source of income
2. Assigned female sex at birth
3. ≥ 18 years of age
4. Living with HIV; diagnosed ≥ 6 months prior
5. Currently living in Durban
6. If on ART, initiated ≥2 months prior

Exclusion Criteria:

1. Engagement in an ongoing HIV treatment research study
2. Planning on leaving Durban for more than 3 months in the following 12 months
3. Pregnant at time of enrollment
4. On a second line or third ART regimen
5. Participating in an adherence club

Sex/Gender

• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Only cisgender women will be enrolled into the study.

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: South Africa

Administrative Information

• NCT Number: NCT03500172
• Other Study ID Numbers: R01NR016650( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Johns Hopkins Bloomberg School of Public Health
• Original Responsible Party: Same as current
• Current Study Sponsor: Johns Hopkins Bloomberg School of Public Health
• Original Study Sponsor: Same as current

Collaborators

• University of the Western Cape
• TB/HIV Care
• University of Toronto
• University of California, San Francisco
• National Institute for Communicable Diseases, South Africa

Investigators

• Principal Investigator: Stefan Baral, MD, MPH; Johns Hopkins Bloomberg School of Public Health
• Principal Investigator: Harry Hausler, MD, MPH; TB/HIV Care

• PRS Account: Johns Hopkins Bloomberg School of Public Health
• Verification Date: November 2022