Study to Evaluate Changes in CD4 on Replacing TDF With ABC or DDI+TDF With ABC+3TC

Study of Changes in CD4 Lymphocyte Count in Patients With a HAART Regimen Including DDI + Tenofovir and With Viral Suppression Following the Replacement of Tenofovir With Abacavir Once Daily or Following the Double Replacement of DDI + Tenofovir With Abacavir + Lamivudine in a Single Tablet

The study aims to ascertain whether the sole replacement of tenofovir with abacavir once a day improves the immunological response obtained with tenofovir + ddI or whether it is better to perform a double replacement of tenofovir and ddI with abacavir + lamivudine (joint formulation) in a single daily dose to achieve these objectives.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Abacavir; Drug: Didanosine; Drug: Abacavir+Lamivudine

Detailed Description

Different works have shown a high rate of virological failure among patients on abacavir + lamivudine + tenofovir or ddI + 3TC + tenofovir, thus rendering the use of these combinations actively unadvisable.

Furthermore, recent studies have also shown that ABC+3TC are associated with a significantly higher increase in CD4 than the current treatment standard formed by AZT+3TC. This provides us with grounds to suppose that patients with TDF+ddI may recover their CD4 with ABC+3HT. Similarly, and recently, the existence of pharmacokinetic interactions between tenofovir + abacavir has begun to be questioned.

Finally, the replacement of tenofovir with abacavir or tenofovir + ddI with abacavir + lamivudine does not detract from the potency of HAART, the toxicity profile is different and their behaviour at mitochondrial level is similar.

This study aims to ascertain whether the sole replacement of tenofovir with abacavir once a day improves the immunological response obtained with tenofovir + ddI or whether it is better to perform a double replacement of tenofovir and ddI with abacavir + lamivudine (joint formulation) in a single daily dose to achieve these objectives.

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Phase 3

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic De Barcelona
  • Barcelona, Spain, 08025
    • Hospital de la Santa Creu i Sant Pau
  • Castello, Spain, 12004
    • Hospital General de Castellón, , Castellón,
  • Gandia, Spain, 46700
    • H. San Fco Borja Gandia
  • Gijon, Spain, 33394
    • Hospital de Cabueñes
  • Granada, Spain, 18012
    • Hospital Clínico San Cecilio
  • Madrid, Spain, 28040
    • Fundación Jiménez Díaz
  • Madrid, Spain, 28040
    • Hospital Clínico San Carlos
  • Santander, Spain, 39008
    • Hospital Marqués de Valdecilla
  • Sevilla, Spain, 41009
    • Hospital Virgen Macarena
  • Tarragona, Spain, 43007
    • Hospital Joan XXIII
  • Valencia, Spain, 46015
    • Hospital Arnau de Vilanova
  • Vigo, Spain, 36204
    • Hospital Xeral de Vigo
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Germans Trias I Pujol Hospital
    • Calella, Barcelona, Spain, 08370
      • Hospital Sant Jaume de Calella
    • Mataro, Barcelona, Spain, 08304
      • Hospital de Mataró
  • Bilabao
    • Bilbao, Bilabao, Spain, 48013
      • Hospital Basurto
  • Cádiz
    • Jerez de la Frontera, Cádiz, Spain, 11407
      • H. del S.A.S. Jerez de la Frontera
  • Granollers
    • Barcelona, Granollers, Spain, 08400
      • Fundació Hospital de Granollers,
  • La Coruña
    • El Ferrol, La Coruña, Spain, 15405
      • Hospital Arquitecto Marcide
  • Santander
    • Torrelavega, Santander, Spain, 39300
      • Hospital Sierrallana

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age > 18 years.
• HIV-1 infected patients.
• Patients on triple HAART therapy including ddI + tenofovir plus a PI or NNRTI for at least 3 months.
• Patients with an undetectable HIV-1 viral load (< 50 copies RNA / mL or < centre's limit of detection) over the last 6 months.
• Not be on treatment with immunosuppressives, such as: hydroxyurea, interferon, ribavirin or cytostatics.
• Not be on treatment with interleukin-2 or other immunomodulators.
• Women may not be of fertile age (defined as at least one year from menopause or undergoing any surgical sterilisation technique), or must undertake to use a barrier contraceptive method during the study.
• Signature of the informed consent.

Exclusion Criteria:

• Incapacity to give informed consent.
• Bad adherence or treatment interruptions over the previous 6 months.
• Prior exposure to abacavir.
• HAART Therapy including ddI at a dose of 400mg + tenofovir if weight > 60 kg or ddI 250 mg + tenofovir if weight < 60 kg.
• Suspicion of cross resistances to abacavir and lamivudine.
• Hepatic or pancreatic analytical alterations 4 times above the limit of normality.
• Presence of opportunistic infections and/or recent tumours (< 6 months).
• Patients participating in another clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: 1; Maintain antiretroviral treatment
Experimental: 2; Change tenofovir to abacavir and increase didanosine dose to 400 mg/day if weight is > 60 Kg. or to 250mg/day if weight is < 60 kg.	Drug: Abacavir; Change tenofovir to abacavir; Other Names: n/h.; Drug: Didanosine; Increase didanosine dose to 400 mg/day if weight is > 60 Kg. or to 250mg/day if weight is < 60 kg.; Other Names: n/h.
Experimental: 3; Change tenofovir and didanosine to abacavir + lamivudine (600mg+300 mg/day in one single tablet).	Drug: Abacavir+Lamivudine; Change tenofovir and didanosine to abacavir + lamivudine (600mg+300 mg/day in one single tablet).; Other Names: n/h.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of patients that increase their number of CD4 lymphocytes with regard to the baseline.	At 12, 24, 36 and 48 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
To evaluate the proportion of patients with viral load of HIV-1 <50 copies of the combinations studied during the follow-up period.	At 12, 24, 36 and 48 weeks.
Incidence of new clinical adverse events that appear .	during 48 weeks of follow-up
Evolution of the clinical adverse events that were already present at the time they were included in the study.	during the 48 weeks of follow-up
Rate of treatment drop-outs due to the appearance of adverse events	during the 48 weeks of follow-up
Incidence of new laboratory alterations that appear during the follow-up period (change in renal parameters, changes in lactate levels, modification of pancreatic enzymes, changes in lipid parameters).	during the follow-up period
Evolution of the laboratory alterations that were already present at the time they were included in the study.	during the 48 weeks of follow-up

Collaborators and Investigators

• Sponsor: Hospital de Granollers
• Investigators: Principal Investigator: Enric Pedrol, MD, PhD, Fundació Hospital de Granollers

Study record dates

Study Major Dates

• Study Start: April 1, 2005
• Primary Completion (Actual): February 1, 2007
• Study Completion (Actual): February 1, 2007

Study Registration Dates

• First Submitted: June 15, 2006
• First Submitted That Met QC Criteria: June 16, 2006
• First Posted (Estimate): June 20, 2006

Study Record Updates

• Last Update Posted (Estimate): March 24, 2015
• Last Update Submitted That Met QC Criteria: March 19, 2015
• Last Verified: October 1, 2008

More Information

Terms related to this study

• Keywords: toxicity; Antiretrovirals; CD4 cell count
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antimetabolites; Lamivudine; Didanosine; Abacavir; Dideoxynucleosides
• Other Study ID Numbers: EUROPA; 2004-003749-42