Interruption thérapeutique programmée chez des patients infectés par le VIH-1 en échec d'un traitement antirétroviral : résultats préliminaires

Abstract

Structured therapeutic interruption (STI) has been offered to HIV-1 infected patients with virological failure (viral load > 1500 copies/mL) of potent antiretroviral therapy (ART) (three or four drugs for at least one year). CD4 lymphocyte count, HIV-1 viral load, clinical status, were assessed every month during STI and after ART reintroduction. Genotype analysis by plasma virus sequencing was done before and after treatment interruption. The results of 14 patients who resumed ART for at least two months are presented. Median duration of STI was 7.5 months (range: 2–13 months). Median CD4 count was low (45/mm 3) when treatment was stopped, and decreased during STI (−37/mm 3 after six months). Several patients exhibited important CD4 diminutions. Viral load slightly increased (+0.83 log at M6). Few clinical events occured: one: severe HIV-related prurigo and one CMV viremia. Reversion of resistance mutations was only seen in 2/13 (15: 4%) patients (who had previously a major CD4 deficiency, and a long treatment history), a partial reversion occured in 5/13 (38.5%) subjects, and the mutations didn't change in the other cases (genotyping non interpretable in the last patient). ART reintroduction induced a good immune response: +56 CD4/mm 3 after six months, with significant increases in 10/14 subjects. There was an initial viral response (median viral load: −2.34 log at M1), but a quick rebound most often occured. However, viral load remained < 50 copies/mL in four patients. In conclusion, a rapid and important decline in CD4 cell count can occur when treatment is discontinued, in patients with virological failure of ART, but the clinical risk appears to be limited. Treatment re-initiation induces a good response, but virologically transient in most cases. Patients with a shift to wild-type virus seem to have a better response.