BONE: STAR (Switching to TAF Based Anti-Retroviral Therapy) Study

Study Overview
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Brief Summary
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The primarily objective of this study is to assess the effect of switching from Tenofovir Disoproxil Fumurate (TDF) to TAF based ART on bone mass and turnover among women on DMPA for contraception. HIV virologically suppressed women on DMPA will be switched from their TDF based regimen to Bictergravir /Emtricitabine / Tenofovir alafenamide (B/F/TAF; Biktarvy®) in a randomized fashion. HIV infected women on TDF and non-hormonal contraception will be switched to Biktarvy®).

Official Title
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A Phase IV Open-Label Trial to Assess Bone Mineral Density in a Cohort of African Women on Depo-provera and Tenofovir Disoproxil Fumurate Switched to Tenofovir Alafenamide Fumarate Based Anti-Retroviral Therapy

Conditions
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Bone Loss

Intervention / Treatment
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* Drug: B/F/TAF
* Drug: TDF/3TC/EFV or DTG or NVP
* Other: DMPA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 20 through 40 years (inclusive) at screening, verified per site SOPs Able and willing to provide written informed consent to be screened for and to take part in the study. Able and willing to provide adequate locator information, as defined in site SOPs Previously participated in the BONE: CARE study. Additional women will be recruited from the health centers where the BONE: CARE participants were receiving HIV care, and these will be matched to those from the BONE: CARE cohort based on age, duration on ART and contraception use. Per participant report, plans to stay in the study catchment area in the next 24 months Per participant report, willing to continue using similar contraceptive method as in the BONE: CARE study. Exclusion Criteria: Currently pregnant/ breastfeeding or was pregnant/ breastfeeding in the last 6 months prior to screening Intentions to get pregnant in the next two years History of active tuberculosis Pathologic bone fracture not related to trauma (ever) Has pre-existing condition known to affect bone metabolism (e.g. thyrotoxicosis, tuberculosis, diabetes mellitus, liver or renal disease) Is taking the following medications known to interfere with bone metabolism (steroids, anti-convulsants, bisphosphonates, cancer drugs, etc.).

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: DMPA+ and TDF+<br>HIV-infected women on DMPA, and TDF containing ART. | Drug: TDF/3TC/EFV or DTG or NVP<br>* A third of the women will remain on Tenofovir Disoproxil Fumurate.(TDF) containing ART.<br>Other: DMPA<br>* Two thirds of the women will be on DMPA for contraception.<br>* Other names: Depo-provera;|
| Experimental: DMPA+ and B/F/TAF+<br>HIV-infected women on DMPA, and B/F/TAF. | Drug: B/F/TAF<br>* A third of the women will be randomized to Bictergravir /Emtricitabine / Tenofovir alafenamide (B/F/TAF; Biktarvy®).<br>* Other names: Biktarvy®);Other: DMPA<br>* Two thirds of the women will be on DMPA for contraception.<br>* Other names: Depo-provera;|
| Experimental: DMPA- and B/F/TAF+<br>HIV-infected women on non hormonal contraception, and B/F/TAF. | Drug: B/F/TAF<br>* A third of the women will be randomized to Bictergravir /Emtricitabine / Tenofovir alafenamide (B/F/TAF; Biktarvy®).<br>* Other names: Biktarvy®);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in bone mineral density | We will assess percent change in BMD among DMPA users who switch to B/F/TAF compared to DMPA users remaining on TDF based ART | 2 years | 
| Changes in trabeculae bone score (TBS) | We will assess percent change in TBS among DMPA users who switch to B/F/TAF compared to DMPA users remaining on TDF based ART | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in bone biomarkers | We will compare changes in bone turnover markers (CTX and P1NP) in B/F/TAF switchers with and without DMPA use | 2 years |