Lopinavir/r Monotherapy Versus Abacavir/Lamivudine and Lopinavir/r for Limb Fat Recovery in Persons With Lipoatrophy (KRETA)
|ClinicalTrials.gov Identifier: NCT00865007|
Recruitment Status : Completed
First Posted : March 19, 2009
Last Update Posted : March 22, 2013
|Condition or disease||Intervention/treatment||Phase|
|HIV Infection Lipodystrophy HIV Infections||Drug: Monotherapy (Lopinavir/ritonavir) Drug: Monotherapy (Lopinavir/ritonavir) + ABC/3TC||Phase 4|
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After more than ten years since it was started, it has already been established that highly-active antiretroviral treatment (HAART) has caused a dramatic reduction in the morbidity and mortality of human immunodeficiency virus (HIV) infection. However, HAART is not exempt of limitations, namely, its toxicity in the long-term; this is of special importance now that treatment of HIV is chronic.
Most common HAART involves the use of two nucleoside reverse transcriptase inhibitors (nucleoside or nucleotide analogues, NRTIs) and either a protease inhibitor (PI) or a non-analogue reverse transcriptase inhibitor (NNRTI). However, there are other regimens that remove some of these families, such as those based on three NRTIs, ZDV+3TC+ABC.
HAART has been associated with a constellation of major metabolic adverse events, such as fat redistribution (lipodystrophy, lipoatrophy, lipohypertrophy-central obesity - or both) and hyperlipidemia (hypercholesterolemia and hypertriglyceridemia).
Lipoatrophy, specifically, occurs as a loss of subcutaneous fat mass in the upper and lower extremities, with the possible appearance of venomegaly in face and buttocks Lipoatrophy is particularly distressing not only for itself, but for its stigma component, affecting the quality of life and the psychological condition of the patient.This also has a direct impact on treatment compliance, that is reduced, and, therefore, at risk that the therapeutic regimen fails to be effective for resistances selection.
Although initially most metabolic adverse events were attributed to PIs, in recent years it has been shown that lipoatrophy specifically is related more to therapy with NRTIs than with PIs; specifically, d4T, ddI and ZDV.
One of the accepted strategies for the management of lipoatrophy in patients receiving therapy with ZDV is its replacement by other NRTI such as TDF or ABC, and consequently, a significant fat recovery is seen.
In a study where therapy with ZDV was discontinued and continued with NNRTIs (lopinavir/ritonavir-LPV/r and nevirapine-NVP) therapy, fat recovery in the extremities seemed to be higher than in patients where ZDV was replaced by ABC.
Lopinavir (ABT-378) is a potent protease inhibitor of HIV. The proven efficacy and safety of LPV/r-based HAART has led to its inclusion since 2003 in therapeutic guidelines as therapy of preferential start PI/r based.
With regard to its relationship with lipoatrophy, recent data have shown that LPV/r has a low risk induction profile.
In recent years data have been published on the use of LPV/r monotherapy: starting, and induction-maintenance after therapy with HAART with sustained undetectability for at least 6 months.
Given the aforementioned data, in those patients developing lipoatrophy while treated with ZDV+ABC+3TC, the approach of switching to a regimen in the absence of LPV/r-based nucleosides could be even more beneficial than just removing ZDV and maintaining them on a HAART containing LPV/r+ABC+3TC. Despite the fact that lipoatrophy associated with ABC/3TC is very low in treatment-naive patients, it has yet to be demonstrated that discontinuing even "benign" nucleosides could provide an additional benefit in patients that had already developed lipoatrophy.
Accordingly, the working hypothesis for this study would be as follows: the recovery or reversion of lipoatrophy would increase in patients receiving LPV/r in monotherapy vs those switching to a classic LPV/r-based HAART. The absence of any nucleoside would then be beneficial for fat recovery in the extremities.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||88 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase IV-III Comparative, Randomized, Open-label Study to Evaluate the Efficacy for the Recovery of Peripheral Fat (or of the Extremities) of Lopinavir/Ritonavir in Monotherapy Versus Abacavir/Lamivudine and Lopinavir/Ritonavir|
|Study Start Date :||December 2008|
|Actual Primary Completion Date :||June 2012|
|Actual Study Completion Date :||September 2012|
Experimental: Monotherapy group
Drug: Monotherapy (Lopinavir/ritonavir)
Active Comparator: Triple arm
Lopinavir/ritonavir (LPV/r)+ ABC/3TC
Drug: Monotherapy (Lopinavir/ritonavir)
Drug: Monotherapy (Lopinavir/ritonavir) + ABC/3TC
NRTI sparing regimen
- Absolute change in limb fat measured by DEXA at 48w [ Time Frame: 48 weeks ]
- Absolute change in limb-fat measured by DEXA at 96 weeks [ Time Frame: 96 weeks ]
- Lipid changes at Week 24, 48, 72 and 96 [ Time Frame: 96 weeks ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00865007
|Hospital Severo Ochoa|
|Leganes, Madrid, Spain, 28911|
|Hospital Xeral Cies|
|Vigo, Pontevedra, Spain, 36204|
|Hospital de Donostia|
|Donostia, San Sebastian, Spain, 20014|
|Hospital de Basurto|
|Bilbao, Vizcaya, Spain, 48013|
|Hospital General Universitario de Alicante|
|Alicante, Spain, 03010|
|Hospital Sant Creu i Sant Pau|
|Barcelona, Spain, 08025|
|Hospital Clinico y Provincial|
|Barcelona, Spain, 08036|
|Hospital Universitario Reina Sofia|
|Cordoba, Spain, 14004|
|Hospital La Paz|
|Madrid, Spain, 28006|
|Hospital Doce de Octubre|
|Madrid, Spain, 28041|
|Hospital La Paz|
|Madrid, Spain, 28046|
|Study Chair:||Jose Ignacio Bernardino||Hospital La Paz|
|Study Chair:||Jose Ramon Arribas||Hospital La Paz|