Clinical trial NCT01153217: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV
Keywords: Tenofovir
HIV-infection
BMD
Osteoporosis
Osteopenia
Lead sponsor: Germans Trias i Pujol Hospital
Sponsor class: OTHER
First posted: 2010-06-30
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Bone mineral density
timeFrame: From baseline to week 48
measure: t-score change
timeFrame: From baseline to week 48
Secondary outcomes:
measure: viral load
timeFrame: Evolution from baseline to week 48
measure: CD4 T lymphocytes count
timeFrame: Evolution from baseline to week 48
measure: Resistance test
timeFrame: If virological failure occurs
measure: Lipid parameters (total, HDL-, LDL-cholesterol and triglyceride levels)
timeFrame: Evolution from baseline to week 48
measure: Adverse Events
timeFrame: From baseline to week 48
Other outcomes:
Locations:
city: Badalona
country: Spain
facility: Lluita contra la SIDA Foundation
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
Study officials:
References:
citation: 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.