Trial to Evaluate the Interest of a Reductive Anti Retroviral Strategy Using Dual Therapy Inspite of Triple Therapy (TRULIGHT)

Regional University Hospital Center (CHRU)

Status and phase: Completed; Phase 3

Conditions: HIV

Treatments: Drug: dual therapy; Drug: triple therapy

Study type: Interventional

Funder types: Other

Identifiers

NCT02302547

PHAO13-TP/TRULIGHT

Details and patient eligibility

About

In the early 2000s, the "TRILEGE©" study was realized to determine if the reductive anti retroviral strategy from an initial triple therapy (based on a protease inhibitor as the third agent) towards a dual therapy of nucleoside analogs (in particular the association of "zidovudine +lamivudine") for patients infected by HIV and stabilized for at least 3 months at a threshold value of 400 copies/ml, would allow to obtain a well-controlled plasmatic viral load, with an aim to reduce the long-term side effects of the treatment.

The afore mentioned study showed that the reductive anti retroviral strategy was a failure. No study has as yet to revaluate this strategy, in particular in the current context of antiretroviral treatments.

Indeed, modern nucleoside inhibitors (Kivexa®, Truvada®) have extended half-lives as well as a superior intrinsic power as compared to treatments proposed in the initial "TRILEGE©" study. Furthermore, the better quality of current triple therapy (as compared to that used 10 years ago) has lead to substantial viral reservoir reduction.

Currently, a small number of patients is being successfully treated in the long-term (viral load < 20 copies/ml) using nucleoside analog dual therapy. The particular characteristics of these patients have yet to be thoroughly investigated.

The patients concerned were all treated prematurely before ever passing below 200 lymphocytes T CD4/mm3. It occurred that all these patients presented a low viral reservoir as measured by HIV DNA quantification (< 2,7 log copies/106 PBMC).

Therefore, by targeting patients who have (1) a strong immune restoration, (2) a low HIV DNA value and (3) a very good observance, the investigators emit the hypothesis that, reductive anti retroviral strategy that would consist in changing from a conventional triple therapy towards a Nucleoside reverse-transcriptase inhibitors dual therapy, could allow for durable control of viral replication with the concomitant benefice of reduced antiretroviral side effects and cost.

Enrollment: 224 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• HIV-1 infected patient
• Initial TT ARV started above (or equal to) 150 / mm3 LT CD4, and 18 months prior to inclusion in the study
• Ongoing antiretroviral therapy combining tenofovir + emtricitabine + a 3rd agent (IP / r, IP, NNRTI, II, Inhibitors) with at least one undetectable viral load (CV <50 copies / mL) after introduction of the latter treatment.
• Patient in virological success: CV <50 copies / mL for at least 12 months, including visit to selection.
• Absence of previous therapeutic failure: no viral load ≥ 200 copies / mL (after 6 months of treatment) (Except in the case of a justified therapeutic interruption: travel, stock-out ...) and of obtaining success Virologic after introduction of treatment, without concept of genotypic resistance known to the ARVs used.
• Cellular DNA-HIV <2.7 log copies / 106 PBMC
• Zenith RNA-HIV <150,000 copies / ml (excluding viral load values during primary infection if it is documented)
• No genotypic resistance to currently used and known ARVs
• Patient who has given written informed consent
• Affiliate or beneficiary of a social security scheme
• Patient followed on an outpatient basis, age ≥ 18 years.

Exclusion criteria

• Non-compliant patient

• Subject is pregnant, or lactating, or of childbearing potential and without contraception

• Active opportunistic infections

• Major overweight (BMI ≥ 40)

• Severe renal pathology (creatinine clearance < 30ml/min)

• Cirrhosis or severe liver failure (factor V < 50%)

• Prognosis threatened within 6 months

• Circumstances that may impair judgment or understanding of the information given to the patient

• Malabsorption syndromes

• The following laboratory criteria:

  • Serum ASAT,ALAT > 5 x upper limit of normal (ULN)
  • Thrombocytopenia with platelet count < 50.000/ml
  • Anemia with hemoglobin < 8g/dl
  • Polynuclear neutrophil count < 500/mm3

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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224 participants in 2 patient groups

triple therapy

Active Comparator group

Description:

Tenofovir Disoproxil Fumarate (nucleotide reverse transcriptase inhibitor) + Emtricitabine (nucleoside reverse transcriptase inhibitor) + third agent (boosted protease inhibitor or unboosted protease inhibitor or integrase inhibitor or celsentri or non-nucleoside reverse transcriptase inhibitor).

Treatment:

Drug: triple therapy

dual therapy

Experimental group

Description:

Truvada®"245mg":oral administration Tenofovir Disoproxil Fumarate (nucleotide reverse transcriptase inhibitor) + Emtricitabine (nucleoside reverse transcriptase inhibitor)

Treatment:

Drug: dual therapy