Multicentre Study To Assess Changes In Bone Mineral Density Of The Switch From Tenofovir To Abacavir In Hiv-1-Infected Subjects With Loss Of Bone Mineral Density

MULTICENTRE STUDY TO ASSESS CHANGES IN BONE MINERAL DENSITY OF THE SWITCH FROM TENOFOVIR TO ABACAVIR IN HIV-1-INFECTED SUBJECTS WITH LOSS OF BONE MINERAL DENSITY

Most of studies have not found any consistent drug-specific association with bone loss and controversial data with respect the effect of protease inhibitors (PIs) have been published. The more evident finding with respect to this issue is the more pronounced decrease of bone mineral density (BMD) in patients during the first weeks of receiving a tenofovir (TDF)-containing regimen, probably by the effect of TDF on phosphorus balance and vitamin D metabolism.

Study Overview

• Status: Completed
• Conditions: HIV
• Intervention / Treatment: Drug: Switch from tenofovir to abacavir

Detailed Description

The prevalence of osteoporosis in HIV-infected patients could be more than three times greater compared with HIV-uninfected subjects, according to the results of a meta-analytical review of cross-sectional published studies. The analysis includes data from 884 HIV-infected patients and 654 HIV-uninfected controls. Sixty-seven percent of HIV population had reduced bone mineral density (BMD), of whom 15% had osteoporosis (OR of 6.4 and 3.7, respectively, compared with HIV-uninfected controls).

In the same meta-analysis, when authors evaluated the role of antiretroviral therapy (ART) on BMD, comparing 202 antiretroviral-naive with 824 ART-treated patients, patients on treatment had a 2.5-fold increased odds of prevalent reduced BMD and osteoporosis. And finally, when 410 non-protease inhibitor (PI)-treated HIV patients were compared with 791 patients receiving a PI-containing regimen, those on PIs had increased odds of reduced BMD and osteoporosis.

As well, other studies support data of an impaired BMD in HIV-infected patients after starting antiretroviral therapy. These results let us confirm that HIV itself and antiretroviral therapy contribute to decrease the BMD.

However, most of studies have not found any consistent drug-specific association with bone loss and controversial data with respect the effect of PIs have been published. The more evident finding with respect to this issue is the more pronounced decrease of BMD in patients during the first weeks of receiving a tenofovir (TDF)-containing regimen, probably by the effect of TDF on phosphorus balance and vitamin D metabolism.

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 3

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08041
    • Hospital de la Santa Creu i Sant Pau
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Lluita contra la Sida Foundation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Adult patients (=/+18 years old) having a diagnosis of HIV-1 infection.
2. Current HAART including tenofovir plus emtricitabine/lamivudine plus a PI, a NNRTI or raltegravir started at least 12 months before.
3. T-score ≤-2 measured by DEXA (within the last 6 months).
4. Maintained undetectable plasma HIV-1 RNA (VL < 50 copies/mL) for at least 12 months.
5. Absence of suspected or documented resistance mutations in the RT associated to abacavir.
6. Voluntary written informed consent.

Exclusion Criteria:

1. History of intolerance, toxicity or virological failure to abacavir.
2. HLA B*5701 positive.
3. Secondary osteoporosis/osteopenia (vitamin D or testosterone deficit, thyroid disease, …)
4. Therapy with biphosphonates within the last 12 months.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Abacavir; Switch from tenofovir to abacavir	Drug: Switch from tenofovir to abacavir; Switch from tenofovir to abacavir; Other Names: Abacavir
No Intervention: tenofovir; Follow same ART regimen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Bone mineral density	From baseline to week 48
t-score change	From baseline to week 48

Secondary Outcome Measures

Outcome Measure	Time Frame
viral load	Evolution from baseline to week 48
CD4 T lymphocytes count	Evolution from baseline to week 48
Resistance test	If virological failure occurs
Lipid parameters (total, HDL-, LDL-cholesterol and triglyceride levels)	Evolution from baseline to week 48
Adverse Events	From baseline to week 48

Collaborators and Investigators

• Sponsor: Germans Trias i Pujol Hospital

Publications and helpful links

General Publications

• Negredo E, Domingo P, Perez-Alvarez N, Gutierrez M, Mateo G, Puig J, Escrig R, Echeverria P, Bonjoch A, Clotet B. Improvement in bone mineral density after switching from tenofovir to abacavir in HIV-1-infected patients with low bone mineral density: two-centre randomized pilot study (OsteoTDF study). J Antimicrob Chemother. 2014 Dec;69(12):3368-71. doi: 10.1093/jac/dku300. Epub 2014 Aug 13.

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: June 29, 2010
• First Submitted That Met QC Criteria: June 29, 2010
• First Posted (Estimate): June 30, 2010

Study Record Updates

• Last Update Posted (Estimate): October 17, 2012
• Last Update Submitted That Met QC Criteria: October 16, 2012
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Keywords: Tenofovir; Osteoporosis; Osteopenia; BMD; HIV-infection
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Tenofovir; Abacavir
• Other Study ID Numbers: OSTEOTENOFOVIR