Effect of Reducing Nucleotide Exposure on Bone Health (ReNew)

Withdrawn before enrolling · Phase 2

Conditions studied: HIV/AIDS, HIV-1-infection, Osteopenia

In brief

This is an open-label, randomized pilot study to assess the effect on bone mineral density (BMD) of a switch from a tenofovir alafenamide-containing antiretroviral regimen to dolutegravir/lamivudine vs. a continuation of the tenofovir alafenamide-containing regimen.

Key facts

Study ID

NCT03549689

Run by

Philip Grant

People needed

0

Starts

2019-08-01

Expected to finish

2021-07-01

Last updated by the study team

2021-03-15

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• HIV-1 infection, as documented by a positive 4th generation assay or by any licensed ELISA test kit confirmed by Western blot at any time prior to study entry.
• Age ≥18 years
• HIV-1 RNA BLQ (e.g., <20 copies/mL or other threshold based on the local viral load assay used) for at least 12 months prior to study entry excluding blips (i.e., a single measurement <200 copies/mL preceded and followed by measurements BLQ)
• On a stable TAF-containing ART that also includes at least 2 other antiretrovirals, with no changes in the 12 months prior to entry (except for a switch to a co-formulated tablet from the component tablets or a switch from ritonavir to cobicistat)
• Lumbar spine, femoral neck or total hip BMD T-score ≤-1.0 from a DXA scan within the past 48 weeks
• If receiving testosterone or estrogen replacement therapy, on a stable dose for ≥3 months prior to enrollment without plan to change dose during the study period.
• Acceptable blood laboratory values at screening visit:
• CD4+ T-cell count ≥200 cells/µL
• Phosphate ≥2mg/dL
• 25-hydroxyvitamin D level ≥10 ng/ml
• Calculated creatinine clearance (CrCl) ≥50 mL/min as estimated by the Cockcroft-Gault equation*:
• For men = CrCl (mL/min) = (140 - age in years) x (body weight in kg) ÷ (serum creatinine in mg/dL x 72)
• For women, multiply the above result by 0.85
• For women of reproductive potential, negative serum or urine pregnancy test prior to screening and a negative urine pregnancy test at the entry visit prior to randomization and agreeable to using a contraceptive of choice during the study period.
• "Women of reproductive potential" are defined as women who have not been post-menopausal for at least 24 consecutive months (i.e., who have had menses within the preceding 24 months) and have not undergone surgical sterilization (i.e., hysterectomy, bilateral oophorectomy, or tubal ligation; participant report sufficient)

You may not qualify if…

• Current systemic glucocorticoid use
• Lumbar spine, femoral neck or total hip BMD T-score <-3.0
• Previous, current pharmacologic treatment, or plan for initiation of therapy for osteoporosis (i.e., bisphosphonates, teriparatide, denosumab, tamoxifen or raloxifene)
• Previous fragility fracture (i.e., any fall from a standing height or less that resulted in a fracture)
• History of genotypic resistance or phenotypic resistance to either DTG or 3TC. The interpretation of genotypic resistance is based on output from the Stanford HIV Resistance Database (available at https://hivdb.stanford.edu). Isolates with an interpretation of low-level resistance or higher are considered resistant.
• History of virologic failure (i.e., confirmed HIV-1 RNA level ≥200 copies/mL after over 6 months of therapy) while on an integrase inhibitor (i.e., raltegravir, elvitegravir, bictegravir, or dolutegravir) or on lamivudine/emtricitabine prior to study enrollment. Any antiretroviral history (even before routine virologic monitoring became standard of care) that would suggest the presence of the M184V mutation should be considered exclusionary
• ALT ≥5 X ULN, OR ALT ≥3xULN and bilirubin ≥1.5xULN (with >35% direct bilirubin)
• Severe hepatic impairment (Child Pugh Class C)
• Anticipated need for antiviral therapy for HCV
• Hepatitis B surface antigen positive or Hepatitis B DNA positive
• Weight >300 pounds, precluding safe DXA testing
• Breastfeeding, pregnancy, or plans to become pregnant during the study
• Known allergy/sensitivity to DTG or 3TC.
• Receipt or planned receipt of prohibited concomitant medications (See section 5.4)
• Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study procedures and treatment.
• Any serious medical or psychiatric illness that, in the opinion of the site investigator, precludes safe participation or adherence to study procedures.

Where it is running

• University of Alabama Birmingham — Birmingham, Alabama, United States
• Stanford University — Palo Alto, California, United States
• University of Colorado — Aurora, Colorado, United States
• Emory — Atlanta, Georgia, United States
• Northwestern — Chicago, Illinois, United States
• Johns Hopkins — Baltimore, Maryland, United States
• Columbia — New York, New York, United States
• Penn — Philadelphia, Pennsylvania, United States
• Dallas VA Medical Center — Dallas, Texas, United States
• UT Houston — Houston, Texas, United States

Full record on ClinicalTrials.gov

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