trial to evaluate the interest of a reductive anti retroviral strategy using dual therapy inspite of triple therapy

Conditions: HIV

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.


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

Keywords: hiv-dna dual therapy nrti virological control truvada®