Lopinavir/r Monotherapy Versus Abacavir/Lamivudine and Lopinavir/r for Limb Fat Recovery in Persons With Lipoatrophy — KRETA  

HIV Infections Clinical Trial

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

Status Completed

Clinical Trial Summary

The aim of this study is to evaluate the efficacy for the recovery of peripheral fat of lopinavir/ritonavir in monotherapy versus abacavir/lamivudine and lopinavir/ritonavir in subjects who developed lipoatrophy while receiving zidovudine plus lamivudine plus abacavir.

Clinical Trial Description

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 Design

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

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infection
• HIV Infections
• Infection
• Lipodystrophy

• NCT number: NCT00865007
• Study type: Interventional
• Source: Fundacion SEIMC-GESIDA
• Status: Completed
• Phase: Phase 4
• Start date: December 2008
• Completion date: September 2012