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

Hospital de Granollers

Status and phase: Completed; Phase 3

Conditions: HIV Infections

Treatments: Drug: Abacavir; Drug: Didanosine; Drug: Abacavir+Lamivudine

Study type: Interventional

Funder types: Other

Identifiers

NCT00338390

EUROPA

2004-003749-42

Details and patient eligibility

About

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.

Full 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.

Enrollment: 75 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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75 participants in 3 patient groups

1

No Intervention group

Description:

Maintain antiretroviral treatment

2

Experimental group

Description:

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.

Treatment:

Drug: Didanosine

Drug: Abacavir

3

Experimental group

Description:

Change tenofovir and didanosine to abacavir + lamivudine (600mg+300 mg/day in one single tablet).

Treatment:

Drug: Abacavir+Lamivudine