Prevention of Lipoatrophy in Patients Treated With Lopinavir/Ritonavir in Monotherapy Versus ZDV + 3TC + ABC
Information source: Fundacion SEIMC-GESIDA
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV Infection; HIV Infections
Intervention: AZT+3TC+ABV (Trizivir) (Drug); Switching to LPV/r monotherapy (Kaletra) (Drug)
Phase: Phase 4
Status: Completed
Sponsored by: Fundacion SEIMC-GESIDA Official(s) and/or principal investigator(s): Jose Antonio Iribarren, Study Chair, Affiliation: Hospital de Donostia
Summary
The aim of this study is to measure the prevention of lipoatrophy in patients treated with
Lopinavir/R in monotherapy versus ZDV + 3TC + ABC
Clinical Details
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
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention
Primary outcome: Limb Fat changes measured by DEXA
Secondary outcome: 20 % loss peripheral fat measured by DEXAPerception of change on body fat by physician and patient. Lipohypertrophy
Detailed description:
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.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Patients infected with HIV 1 documented by positive HIV 1 antibody test and/or
positive PCR test confirmed for HIV 1 RNA.
- Patients on treatment with Trizivir with an undetectable viral burden defined as < 50
copies/ml in the past 6 months.
- Men or women aged ≥ 18 years.
- CD4 cell count ≥ 200 cells/μl.
- For women of child bearing age, a negative urine pregnancy test at the screening
visit.
- Patients giving their written informed consent before completing any study specific
screening procedure.
Exclusion Criteria:
- Patients with previously failed therapy with protease inhibitors (PI) or those
receiving sub optimum therapy with nucleoside analogue reverse transcriptase
inhibitors (NRTI) for the study disease.
- Presence of lipoatrophy defined by the investigator (any grade) or by the patient (in
this case, at least two sites of mild degree or one of at least moderate degree).
- Known history of drug addiction or chronic use of alcohol that, in the investigator's
opinion, contraindicates participation in the study.
- Pregnant or nursing women or women of child bearing age not using an adequate
contraceptive method according to the investigator's criterion.
- Current active opportunistic infection or documented infection in the 4 weeks prior
to screening.
- Renal disease with creatinine clearance < 50 ml/min.
- Concomitant use of nephrotoxic or immunosuppressive agents.
- Patient currently treated with systemic corticosteroids, interleukine 2, or
chemotherapy.
- Patients treated with other investigational agents.
- Patients with acute hepatitis.
- Any disease that, at the criterion in the investigator, contraindicates the patient's
participation in the study.
Locations and Contacts
Hospital Doce de Octubre, Madrid 28041, Spain
Hospital La Paz, Madrid 28046, Spain
H. Son Dureta, Mallorca, Spain
Hospital Ntra.Sra. de Zumarraga, Zumarraga, Guipuzcua 28700, Spain
Hospital Severo Ochoa, Leganes, Madrid 28911, Spain
Hospital de Donostia, Donostia, San Sebastian 20014, Spain
Hospital de Basurto, Bilbao, Vizcaya 48013, Spain
Additional Information
Starting date: December 2008
Last updated: September 11, 2013
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