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

• Status: Completed
• Trial end date: 2018-09-21
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University Hospital, Tours
• Collaborators: Central Hospital, Nancy, France; Central Hospital, NIORT; Centre Hospitalier de La Rochelle; Henri Mondor University Hospital; HOSPITAL, CAEN; HOSPITAL, CHARTRES; HOSPITAL, FOCH; HOSPITAL, HENRI MONDOR; HOSPITAL, HOTEL DIEU; HOSPITAL, NIORT; HOSPITAL, ORLEANS; HOSPITAL, SAINT LOUIS; HOSPITAL, SAINTES; Poitiers University Hospital; Tenon Hospital, Paris; Tourcoing Hospital; University Hospital, Rouen
• Treatments: Atazanavir Sulfate; Cobicistat; Darunavir; Dolutegravir; Efavirenz; Elvitegravir; Emtricitabine; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Enfuvirtide; Etravirine; Fosamprenavir; HIV Protease Inhibitors; Indinavir; Integrase Inhibitors; Lopinavir; Maraviroc; Nevirapine; Protease Inhibitors; Raltegravir Potassium; Reverse Transcriptase Inhibitors; Rilpivirine; Ritonavir; Saquinavir; Tenofovir; Tipranavir

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