Clinical trial NCT03500172: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV-1 Virologic Response
Keywords: HIV
Female Sex Workers
Viral Suppression
South Africa
Decentralized care
Antiretroviral therapy
Differentiated care
Lead sponsor: Johns Hopkins Bloomberg School of Public Health
Sponsor class: OTHER
Collaborators: name: University of the Western Cape
name: TB HIV Care
name: University of Toronto
name: University of California, San Francisco
name: National Institute for Communicable Diseases, South Africa
First posted: 2018-04-17
Enrollment: 1391
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
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).
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Percentage of Participants Retained and Virally Suppressed Among Those Receiving the DTP Versus ICM Arms
timeFrame: 18 months after enrollment
Secondary outcomes:
measure: Retention and Viral Suppression of Non-Responders
timeFrame: 18 months after enrollment
measure: Risk Factors of Loss to Follow-up
timeFrame: Up to 18 months after enrollment
measure: Durability of Retention and Viral Suppression of Responders
timeFrame: Up to 18 months after enrollment
measure: Adherence Assessment
timeFrame: 18 months
measure: Viral Suppression of Retained
timeFrame: Up to 18 months after enrollment
measure: Loss-to-Follow-Up
timeFrame: 18 months after study enrollment
measure: Intervention Acceptability
timeFrame: Acceptability of each intervention at 6 month timepoint
measure: 2nd/3rd Line ART
timeFrame: Up to 18 months after enrollment
measure: ART Resistance
timeFrame: Up to 18 months after enrollment
measure: Comparative Cost-effectiveness of Intervention
timeFrame: Up to 18 months after enrollment
Other outcomes:
measure: Decentralized Treatment Provision (DTP) Pick-Ups
timeFrame: Up to 18 months after enrollment
measure: ICM Phone-Based Contacts
timeFrame: Up to 18 months after enrollment
measure: ICM In-Person Meetings
timeFrame: Up to 18 months after enrollment
Locations:
city: Durban
country: South Africa
facility: TB HIV Care
Study officials:
affiliation: Johns Hopkins Bloomberg School of Public Health
name: Stefan Baral, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: TB HIV Care
name: Harry Hausler, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.