Immuno-Virological Efficacy of Combination With Trizivir +Tenofovir in Multiresistant HIV Patients

Open-Label, Single-Centre, Randomised Pilot Study to Evaluate Immunovirological and Clinical Evolution of a Combination With Nucleoside Analogues/Nucleotides (Trizivir +Tenofovir) in Multiresistant Patients With Virological Failure

To evaluate whether the combined therapy of two nucleosides plus one nucleotide (Trizivir + TDF) manages to keep CD4 lymphocytes stable in patients with HIV infection on antiretroviral treatment that present virological failure and multiple resistance to antiretrovirals.

This study has been designed to determine whether the use of a regimen based exclusively on NTRI, containing tenofovir, zidovudine and lamivudine, is able to preserve immunological status in patients with detectable viral load for whom an efficacious salvage regimen cannot be designed, slowing the progression of the viral load and reducing antiretroviral treatment-associated toxicity. In order to complete the salvage regimen without increasing the number of tablets too much, Trizivir plus tenofovir as investigational treatment will be used.

Inclusion Criteria:

1. Age>= 18 years.

2. HIV-1 infected patients.

3. Patients on antiretroviral treatment including NTRI + PI +/- NNRTI +/- fusion inhibitors at inclusion in the study.

4. Virological failure, defined as 2 determinations with viral load >1,000 copies/mL in the last 6 months, during stable HAART therapy over the previous 6 months.

5. Genotype or phenotype resistance to three families of antiretrovirals (PI, NTRI and NNRTI) demonstrated in genotype study carried out in the last 48 weeks and defined as:

   • 3 or more TAMS of the following: M41L, E44D, D67N, V118I, L210W, T215Y/F, K219Q/E.
   • Existence of the M184V mutation or probable presence in the cellular archives.
   • 5 or more mutations that confer resistance to PI of the following: I10F/I/R/V, V32I, M46I/L, I54V/M/L, V82A/F/T/S/V, I84V/A/C, L90M.
   • Existence of 1 or more mutations that confer resistance to NNRTI, or probable presence in the cellular archives of: K103N, Y181C/I/Y, G190S/A/G.

6. CD4 lymphocytes >- 300 cells/mm3 in the last two determinations.

7. Subject able to follow the treatment period.

8. Acceptance of the study and signature of the informed consent form.

9. 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.

Exclusion Criteria:

• Suspicion of previous incorrect adherence.
• Pregnancy or breastfeeding
• Suspicion of intolerance to any investigational drug.
• Record of any disease which, according to clinical criteria, may reoccur with the proposed change of therapy (sarcoma, lymphoma, etc).
• CD4 Nadir below 200 cel/mm3.
• Acute intercurrent disease or fever in the 15 days before inclusion.