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

NCT02302547

CompletedPhase 3

Sponsor: University Hospital, Tours

Conditions: HIV

Interventions: triple therapy, dual therapy

Countries: France

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.

Eligibility overview

Sex: ALL

Age: 18 Years to

Healthy volunteers: No

Study type: INTERVENTIONAL

Eligibility criteria
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
Locations (16)
  • Caen, France
  • CHR d'ORLEANS, France
  • Créteil, France
  • La Rochelle, France
  • Le Coudray, France
  • Nancy, France
  • Niort, France
  • Paris, France
  • Paris, France
  • Paris, France
  • Poitiers, France
  • Rouen, France
  • Saintes, France
  • Suresnes, France
  • Tourcoing, France
  • Tours, France