Bone Health in Aging HIV Infected Women
Condition: Osteoporosis; HIV; Menopause
MeSH terms: Osteoporosis
Intervention: tenofovir-alafenamide-emtricitabine; tenofovir-emtricitabine
Intervention description: comparison of tenofovir-emtricitabine and tenofovir-alafenamide-emtricitabine on bone mineral density; comparison of tenofovir-emtricitabine and tenofovir-alafenamide-emtricitabine on bone mineral density
Intervention MeSH terms: Tenofovir; Emtricitabine
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 34.0
Sex: Female
Minimum age: 40 Years
Maximum age: 60 Years
Healthy volunteers: No
Keywords: kidney, antiretroviral agent, tenofovir, osteoporosis, women

Summary:

      Design: Open-label randomised multicenter international strategic trial of older women on
      combination antiretroviral therapy (cART) containing tenofovir-emtricitabine (TDF/FTC) with
      HIV RNA suppression for > 6 months to : 1. Immediate switch of TDF/FTC to tenofovir
      alafenamide-emtricitabine (TAF/FTC) while continuing the third antiretroviral agent.; 2.
      Delayed switch; with switch of TDF/FTC to TAF/FTC at 48 weeks while continuing the third
      agent. Follow up of all subjects to 96 weeks.

      Subject Population: The anticipated sample size is 128 HIV infected women aged 45-55 years
      (peri or early post menopause). .

      Primary endpoint: Percentage change from baseline bone mineral density (BMD) at the lumbar
      spine at weeks 48 and 96.

      Secondary Endpoints: BMD change at hip, trabecular bone score, estimated bone strength by
      high resolution peripheral quantitative computerized tomography (HR-pQCT), muscle quality,
      geriatric assessment; biomarkers of bone, immune activation and inflammation; HIV viral
      suppression; safety, lipid and renal function, cardiovascular risk scores at weeks 48 and 96.

      Expected Outcomes: To determine if a switch from TDF/FTC to TAF?FTC improves BMD to a degree
      correlating with a decreased risk of fragility fracture in aging HIV infected women.
      Secondary outcomes will assess bone strength using new imaging modalities, timing of switch,
      and renal health. This data will be used by health policy makers and providers to determine
      the proper use of TAF/FTC in the aging HIV population.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Biological female aged 40-60

          2. Documented HIV-1 infection

          3. Peri-menopausal ( as documented by history).

          4. Signed Informed Consent Form and willing to comply with the protocol.

          5. Receiving a cART regimen containing a ritonavir boosted PI (darunavir, atazanavir,
             lopinavir,) or an NNRTI (efavirenz, nevirapine or rilpivirine) or an integrase
             inhibitor (dolutegravir or raltegravir or elvitegravir) in combination with TDF-FTC
             for > 24 weeks.

          6. Stable viral suppression (plasma HIV-RNA<50 copies/mL for > 24 weeks). Single viral
             blip <500/ml allowed if re-suppresses.

          7. If of childbearing potential, is using effective birth control methods and is willing
             to continue during the trial.

          8. Women will be assessed for vitamin D and calcium dietary intake; if inadequate for
             age, supplements will be recommended.

        Exclusion Criteria:

          1. HIV-2

          2. High 10-year fracture risk at baseline ( > 20%) based on country specific FRAX

          3. Current treatment with active bone medications- bisphosphonates, denosumab,
             calcitonin, raloxifene, teriparatide, strontium

          4. Current use of systemic steroids ( inhaled steroids permitted) or chemotherapeutic
             agents

          5. Acute viral hepatitis

          6. Chronic hepatitis C with liver transaminases >5 x ULN or expected to require treatment
             for hepatitis C during the trial period.

          7. Any investigational ARV within 30 days.

          8. Dialysis or renal insufficiency (creatinine clearance < 50ml/min)

          9. History of decompensated liver disease (AST or ALT≥5x the upper limit of normal (ULN)
             or ALT ≥ 3 x ULN and bilirubin ≥ 1.5 x ULN with > 35% direct bilirubin), or the
             presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or
             gastric varices.

         10. Pregnant or breastfeeding

         11. Screening blood result with any grade 3/4 toxicity according to Division of AIDS
             (DAIDS) grading scale, except: asymptomatic grade 3 amylase, creatinine phosphokinase,
             or lipid elevation.

         12. Any condition (including illicit drug use or alcohol abuse) or lab results which, in
             the investigator's opinion, interfere with assessments or completion of the trial.