Trial To Assess The Lipid-Lowering Effect Of Adding Tenofovir/Emtricitabine Co-Formulation Vs Placebo To Hiv-1-Infected Subjects With Dyslipidemia And Sustained Viral Load Suppression Under Monotherapy With Ritonavir-Boosted Protease Inhibitors

This is a phase IV, multicenter,, prospective, randomised, crossover, double blind, placebo-controlled and proof of concept clinical trial. The trial was conducted in a total sample of 60 patients (30 patients per group), which assures adequate power to detect differences. This study is adequate to demonstrate the lipid-lowering effect of TDF/FTC co-formulation addition in patients with dyslipidemia and stable monotherapy antiretroviral treatment.

All subjects fulfilling inclusion criteria will be randomised to add either TDF/FTC co-formulation (group A) or placebo (Group B) to their current PI/r regimen, i.e.: DRV/r 800/100 mg QD or LPV/r 400/100 BID. This will be followed by a crossover addition of TDF/FTC co-formulation or placebo.

In Group A the expected changes in cholesterol values, regarding baseline, can be observed 3 months after TDF/FTC addition. After this, a period of 3 months with placebo will act as a washout period, allowing establishing comparisons intra-patient. Finally, another period of 3 months with placebo will permit to establish comparisons with the first 3-month TDF/FTC intervention. In Group B, subjects will follow a 3-month placebo period, later a 3-month TDF/FTC intervention and finally a placebo period that will act as a wash-out.

Randomization will be centralised in the CRO FLS-Research Support and will be stratified by DRV/r or LPV/r intake at baseline to ensure equal distribution in both arms. TDF/FTC co-formulation or Placebo will be provided in a double-blinded fashion, i.e.: neither the treating physician nor the patient will know whether the patient is receiving TDF/FTC or placebo.

All subjects will receive dietary counselling to promote lipid-lowering diet provided by a specialised dietician throughout the study.

The expected duration of the study for each participant will be 36 weeks. There will be 6 visits: screening, baseline and weeks 4, 12, 24 and 36.

The date for the inclusion of the first patient was November 2011 and the end of the last patient follow-up has been in February 2014. The enrolment period has been 18 months. The final study report will be submitted before November 2014.

Inclusion criteria

• Age ≥ 18 years
• Chronic HIV-1 infection
• Antiretroviral treatment with either DRV/r (800/100 mg QD) or LPV/r (400/100 mg BID) monotherapy during at least 6 months prior to screening.
• Fasting total cholesterol or LDL-cholesterol levels ≥ 200 and ≥130 mg/dL respectively, in the previous two consecutive tests obtained at least 4 weeks apart before screening.
• Calculated creatinine clearance ≥ 60 mL/min, according to the Cockcroft-Gault formula.
• Undetectable plasma HIV-1 RNA levels (< 50 copies/mL) during at least 6 months prior to screening.
• Adequate treatment adherence.
• Absence of TDF or FTC resistances.
• Written informed consent to participate into the study.

Exclusion criteria

• Acute infections or uncontrolled chronic infection in the 2 months previous to the inclusion or physical examination that, in the investigator's opinion, would compromise the patient's safety or outcome of the study
• Lactating, pregnancy or fertile women willing to be pregnant.
• Concomitant use of any drug with potential drug-drug interaction with DRV/r, LPV/r or TDF/FTC co-formulation at study entry.
• Concomitant use of any lipid-lowering drugs at study entry.
• Prior documented intolerance or hypersensitivity to TDF, FTC, LPV/r or DRV/r.
• Therapies including interferon, interleukin-2, cytotoxic chemotherapy or immunosuppressors at study entry.
• Acute or chronic renal documented pathologies.
• Documented resistance to any of the study drugs (either genotypic or phenotypic)
• Life expectancy less or equal to 1 year.
• Current alcohol or substance use judged by the investigator to potentially interfere with subject study compliance.
• Subjects currently taking part in any other clinical trial using an investigational product, with the exception of studies where the treatment studied have stopped for more than 12 weeks.
• Any other clinical condition or prior therapy that, in the opinion of the investigator, would make the subject unsuitable for the study or unable to comply with the dosing requirements.