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

HIV Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01153217
• Other study ID #: OSTEOTENOFOVIR
• Status: Completed
• Phase: Phase 3
• First received: June 29, 2010
• Last updated: October 16, 2012
• Start date: July 2010
• Est. completion date: June 2012

Study information

• Verified date: October 2012
• Source: Germans Trias i Pujol Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 54
• Est. completion date: June 2012
• Est. primary completion date: June 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV

Intervention

Drug:
• Switch from tenofovir to abacavir
Switch from tenofovir to abacavir

Locations

Country	Name	City	State
Spain	Lluita contra la SIDA Foundation	Badalona	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona

Sponsors (1)

Lead Sponsor	Collaborator
Germans Trias i Pujol Hospital

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Bone mineral density		From baseline to week 48	No
Primary	t-score change		From baseline to week 48	No
Secondary	viral load		Evolution from baseline to week 48	Yes
Secondary	CD4 T lymphocytes count		Evolution from baseline to week 48	No
Secondary	Resistance test		If virological failure occurs	No
Secondary	Lipid parameters (total, HDL-, LDL-cholesterol and triglyceride levels)		Evolution from baseline to week 48	No
Secondary	Adverse Events		From baseline to week 48	Yes