Prevention of Lipoatrophy in Patients Treated With Lopinavir/Ritonavir in Monotherapy Versus ZDV + 3TC + ABC (KALIPO)
The aim of this study is to measure the prevention of lipoatrophy in patients treated with Lopinavir/R in monotherapy versus ZDV + 3TC + ABC
Drug: AZT+3TC+ABV (Trizivir)
Drug: Switching to LPV/r monotherapy (Kaletra)
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
|Official Title:||A Randomized Comparative Clinical Trial of ZDV + 3TC + ABC (Trizivir) vs Monotherapy With Lopinavir/R (Kaletra) in Patients With Viral Suppression on Previous Treatment With ZDV + 3TC + ABC (Trizivir) for Preventing Lipoatrophy|
- Limb Fat changes measured by DEXA [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
- 20 % loss peripheral fat measured by DEXA [ Time Frame: 96 weeks ] [ Designated as safety issue: Yes ]
- Perception of change on body fat by physician and patient. [ Time Frame: 96 weeks ] [ Designated as safety issue: Yes ]
- Lipohypertrophy [ Time Frame: 96 weeks ] [ Designated as safety issue: Yes ]
|Study Start Date:||December 2008|
|Study Completion Date:||March 2013|
|Primary Completion Date:||March 2013 (Final data collection date for primary outcome measure)|
No Intervention: TZV (Trizivir)
Keeping on TZV in patients with viral suppression
Switching to LPV/r monotherapy
Drug: AZT+3TC+ABV (Trizivir)
Patients on treatment with TZV and viral suppression will be randomized to keep on TZV vs switching to LPV/r monotherapy
Other Names:Drug: Switching to LPV/r monotherapy (Kaletra)
Patients on AZT+3TC+ABV with viral suppression will be randomized to keep on vs switching to LPV/r
Other Name: Kaletra
In recent years mayor progress has been made in therapeutic approaches with the introduction of HAART, which has meant a huge fall in morbidity-mortality in Western countries.
However, despite having a variety of potent HAART combinations, some patients do not obtain adequate suppression. The causes of virological failure are complex, and one of the most significant factors is the incomplete compliance with the prescribed dosage of highly-active antiretroviral therapy (HAART). The development of fixed dose combination products is most commonly used to help simplify the dosages and improve treatment compliance.
One of the main problems associated with the treatment of HIV infection is the change in body structure, generally grouped under the term of lipodystrophy. These usually include fat accumulation in the stomach, or abdominal girth, and, even worse, atrophy in the face, arms, and legs. It is usually associated with metabolic disorders, with increased levels of triglycerides, cholesterol and/or insulin resistance.
The incidence of lipodystrophy increases progressively over time in patients starting treatment with antiretroviral agents. It is estimated that, after 2 years of treatment, 20%-30% of patients experience moderate or severe lipodystrophy.
Trizivir® is a combination of three antiretroviral agents: Abacavir, Lamivudine and Zidovudine in a tablet. All of them belong to the group of nucleoside/nucleotide analogue reverse transcriptase inhibitors (NRTIs.
The main advantage of Trizivir is the possibility of simplifying antiretroviral treatment. Multiple studies have been performed showing that simplification of HAART with Trizivir enhances compliance and improves quality of life in patients maintaining the efficacy of previous antiretroviral treatments.
Kaletra® (lopinavir+ritonavir) is a combination of two protease inhibitors: lopinavir plus a low dose of ritonavir, enhancing the action of the former.
Previous studies have shown that most patients treated with Kaletra monotherapy have an undetectable viral load after 48 weeks. Monotherapy failures were not associated with the development of primary resistance mutations.
To date the development of lipoatrophy appears to occur more frequently in patients with a NRTI- containing regimen. The combination of abacavir, zidovudine and lamivudine has been investigated in patients naive to antiretroviral treatments and in patients already treated with NRTIs.
In this setting, we designed this clinical trial to establish the potential benefit of Kaletra in monotherapy for the prevention of lipoatrophy. For this purpose, we will compare keeping on treatment with TZV in patients with viral suppression vs switching to Kaletra in monotherapy in order to prevent fat changes.
Since the purpose of the study is to establish the ability of Kaletra to prevent the development of and exclude patients with acute intolerance to Kaletra, the patients assigned to the experimental group will be treated for 4 weeks with Trizivir and Kaletra before switching to Kaletra monotherapy.
|Hospital Ntra.Sra. de Zumarraga|
|Zumarraga, Guipuzcua, Spain, 28700|
|Hospital Severo Ochoa|
|Leganes, Madrid, Spain, 28911|
|Hospital de Donostia|
|Donostia, San Sebastian, Spain, 20014|
|Hospital de Basurto|
|Bilbao, Vizcaya, Spain, 48013|
|Hospital La Paz|
|Madrid, Spain, 28046|
|Hospital Doce de Octubre|
|Madrid, Spain, 28041|
|H. Son Dureta|
|Study Chair:||Jose Antonio Iribarren||Hospital de Donostia|