Bone Mineral Density in Human Immunodeficiency Virus Type 1 (HIV-1)-Infected Adult Subjects Switching From a Tenofovir Regimen to a Dolutegravir Plus Rilpivirine Regimen
Condition: HIV Infections
MeSH terms: HIV Infections
Intervention: Subjects do not receive study medication in this study 202094
Intervention description: Participants do not receive study medication in this study 202094.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 102.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: tenofovir disoproxil fumarate; dolutegravir plus rilpivirine; two-drug regimen; bone mineral density; dual energy X-ray absorptiometry (DEXA); Human Immunodeficiency Virus-1; nucleoside reverse transcriptase inhibitor -sparing regimen; integrase inhibitor

Summary:

      The purpose of this study is to evaluate any change from baseline in bone mineral density
      (BMD) in subjects following the switch from a triple antiretroviral therapy (ART) regimen
      containing Tenofovir disoproxil fumarate (TDF) to the nucleoside reverse transcriptase
      inhibitor (NRTI) - sparing two - drug regimen of dolutegravir (DTG) + rilpivirine (RPV) in
      subjects participating in the parent studies 201636 and 201637 (SWORD-1 and SWORD-2).

      This open-label, parallel group, study is a sub-study which will recruit subjects who are
      receiving ART regimens which include TDF at the time of randomization to receive treatment in
      one of two identical parent studies 201636 and 201637 (SWORD-1 and SWORD-2). These are Phase
      III, randomised, open-label, multicentre, parallel-group, non-inferiority studies evaluating
      the efficacy, safety, and tolerability of switching to DTG plus RPV from current integrase
      inhibitor (INI)-, non NNRTI-, or protease inhibitor (PI)-based antiretroviral regimen in
      HIV-1-infected adults who are virologically suppressed, having HIV-1 ribonucleic acid (RNA)
      levels <50 copies per millilitre (c/mL). Randomisation in the parent studies will be
      stratified by baseline third agent class (INI, NNRTI, or PI), age group (< or =>50 years old)
      and participation in this Dual energy X-ray absorptiometry (DEXA) sub-study, therefore there
      will also be balance across the treatment arms in this sub-study both overall and with
      respect to baseline third agent class and age at entry.

      The study population will include approximately 75 evaluable subjects recruited from the
      Early Switch DTG + RPV treatment group of the parent studies 201636 and 201637, and
      approximately 75 evaluable subjects from the Late Switch group who continue their current
      antiretroviral therapy (CAR) through to Week 52 across both the 201636 and 201637 (SWORD-1
      and SWORD-2) studies. Subjects participating in study 202094 will have DEXA scans performed
      at Day 1 and at study Weeks 48, 100 and 148 in parallel with the corresponding scheduled
      visits in the parent studies.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Screened and eligible but not yet randomised to either of the parent studies 201636
             (SWORD-1) or 201637 (SWORD-2)

          -  Receiving an ART regimen which contains TDF

          -  Female subjects of child bearing potential with a negative pregnancy test at both
             Screening and Day 1 and agrees to use one of the methods of contraception described in
             the protocols of the parent studies 201636 (SWORD-1) and 201637 (SWORD-2) to avoid
             pregnancy. Any contraception method must be used consistently, throughout the study
             period in accordance with the approved product label, including adherence to
             appropriate 'run in' periods for hormonal contraception

          -  Subject is willing and able to understand the requirements of study participation and
             provide signed and dated written informed consent prior to Screening. Subject is
             considered an appropriate candidate for participation in this study

          -  For subjects enrolled in France: a subject will be eligible for inclusion in this
             study only if either affiliated to or a beneficiary of a social security category

        Exclusion Criteria:

          -  Less than three vertebra in the range of L1 to L4 that are suitable for BMD
             measurement by DEXA scan

          -  Bilateral hip replacement

          -  Uncontrolled thyroid disease: thyroid stimulating hormone (TSH) above normal range,
             and considered to indicate a requirement for thyroid replacement therapy

          -  Male hypogonadism: serum testosterone < 300 nanogram per decilitre (ng/dL) on a sample
             collected before 10:00 in the morning and the subject is able and willing to start
             testosterone replacement therapy

          -  Endocrine diseases including Cushing's syndrome and diabetes mellitus

          -  History of fragility fractures

          -  Ever treated for osteoporosis with bisphosphonates, oestrogen receptor modulators or
             other therapies, and / or severe osteoporosis as indicated by a prior DEXA scan
             derived T-score of -3.5 or lower value

          -  Body mass index (BMI) < 18 kilogram per meter (kg/m)^2 or =>40 kg/m^2

          -  Vitamin D deficiency: 25 Hydroxy Vitamin D < 15ng/mL

          -  Any pre-existing physical or mental condition (including substance abuse disorder)
             which, in the opinion of the investigator, may interfere with the subject's ability to
             comply with the scheduled protocol evaluations or which may compromise the safety of
             the subject

          -  Current use or intent to initiate, tamoxifen, bone-related treatment, e.g.
             biphosphonates, osteoporosis medications including selective oestrogen receptor
             modulator medicines (raloxifene, arzoxifene and lasofoxifene), growth hormone or
             anabolic steroids, except for testosterone as specified below, during the study period

          -  The following are excluded unless they have been given for at least 6 months prior to
             Day 1, and there is no plan to stop them during the study: Anti-convulsant therapy and
             hormonal therapy, including female hormone replacement therapy or testosterone as a
             replacement therapy or supplement

          -  Women who are pregnant, breastfeeding or who plan to become pregnant or breast feed
             during the study period

          -  Subject enrolled, or anticipated to be selected to participate following study
             registration, in an investigational clinical protocol/s in addition to one of the
             parent studies 201636 or 201637 (SWORD-1 or SWORD-2)