Multicentre Study To Assess Changes In Bone Mineral Density Of The Switch From Protease Inhibitors To Dolutegravir In HIV-1-Infected Subjects With Low Bone Mineral Density

Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia

Status and phase: Completed; Phase 3

Conditions: HIV-1 Infection

Treatments: Drug: Dolutegravir, 50mg every 24 hours; Drug: Protease Inhibitor/ritonavir

Study type: Interventional

Funder types: Other

Identifiers

NCT01966822

OSTEODOLU

Details and patient eligibility

About

Protease inhibitors (PI) have been associated with an acceleration of bone mineral density loss in HIV-infected individuals because of an enhanced osteoclast activity, although some controversial data have been also published. A first study suggest an increase of bone mineral density after switching from PI to raltegravir, the first generation integrase inhibitor, but there are no more data about this subject.

Based on data that PI decrease bone mineral density by accelerating osteoclast cells and that the discontinuation of this drugs could improve bone mineralization, we propose a randomized prospective multicenter study to assess the impact of switching from PI to dolutegravir on bone mineral density in patients with low bone mineral density receiving a PI-containing regimen. At the same time, the study will help to assess the antiviral efficacy and safety of a PI-sparing regimen including dolutegravir as a simplification strategy in virologically suppressed patients.

Full description

The second generation integrase inhibitor dolutegravir has demonstrated good virological and immunological outcomes in antiretroviral-naive subjects, compared with efavirenz, (SPRING 1 study). As well, it is active against HIV strains resistant to first-generation inhibitors raltegravir and elvitegravir in heavily treatment-experienced patients (VIKING study).

Additionally, it was safe and well tolerated after two years of use. It is administered once daily with no need for boosting, no food requirements and has a long half-life. The easy posology and its pharmacokinetics, together with the antiviral potency, make this drug a good alternative as a simplification approach. However, no clinical data are available supporting the switch of protease inhibitors or no nucleoside reverse transcriptase inhibitors to dolutegravir in virologically suppressed HIV-treated subjects.

Protease inhibitors (PI) have been associated with an acceleration of bone mineral density loss in HIV-infected individuals because of an enhanced osteoclast activity, although some controversial data have been also published. A first study suggest an increase of bone mineral density after switching from PI to raltegravir, the first generation integrase inhibitor, but there are no more data about this subject.

Based on data that PI decrease bone mineral density by accelerating osteoclast cells and that the discontinuation of this drugs could improve bone mineralization, we propose a randomized prospective multicenter study to assess the impact of switching from PI to dolutegravir on bone mineral density in patients with low bone mineral density receiving a PI-containing regimen. At the same time, the study will help to assess the antiviral efficacy and safety of a PI-sparing regimen including dolutegravir as a simplification strategy in virologically suppressed patients.

Enrollment: 75 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. HIV-infected patients over 18 years.
2. In current antiretroviral therapy with abacavir and lamivudine (Kivexa) plus ritonavir-boosted PI, at least 6 months.
3. Viral suppression (HIV RNA <50 copies / ml) for at least 12 months.
4. T-score ≤ -1 evaluated by DEXA (done in the last 6 months).
5. Signed informed consent.
6. In potential childbearing women, commitment to use barrier contraceptive method throughout the study.

Exclusion criteria

1. Suspected or documented resistance to integrase inhibitors or reverse transcriptase inhibitors, nucleoside analogues.
2. Osteoporosis / osteopenia secondary (testosterone deficiency, thyroid disease ...), except vitamin D deficiency
3. Treatment with bisphosphonates in the last 6 months.
4. Have used integrase inhibitors
5. Pregnant or breastfeeding.
6. Patients with alanine aminotransferase (ALT)> 5 times the upper limit of normal (ULN) or ALT ≥ 3 times ULN and bilirubin ≥ 1.5 times ULN (direct bilirubin> 35%)
7. Patients with severe hepatic dysfunction (Class B or C) according to the Child-Pugh classification
8. Patients infected with hepatitis B virus (HBV) who can not use entecavir or telbivudine.
9. Patients infected with hepatitis C virus (HCV) in which is expected to begin treatment during the study.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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75 participants in 2 patient groups

Dolutegravir 50mg

Experimental group

Description:

Dolutegravir 50mg every 24 hours + Kivexa (ABC+3TC)

Treatment:

Drug: Dolutegravir, 50mg every 24 hours

Protease Inhibitor/ritonavir

Active Comparator group

Description:

Protease Inhibitor/ritonavir + Kivexa (ABC+3TC)

Treatment:

Drug: Protease Inhibitor/ritonavir