OBJECTIVE During 1999, first-line antiretroviral combinations for the treatment of HIV infections have diversified. The aim of our study was two-fold: define the factors associated with initial success and define the factors associated with virological rebound in patients in whom a primary antiretroviral therapy (ARV) had been initiated between 1999 and 2000. METHODS We conducted a retrospective multicenter study regrouping 6 HIV clinics in the North-East of France. Data were Issued from the patients medical files. Primary success was defined as plasma HIV RNA viral load (VL<200 copies/ml within 6 Months of therapy and two consecutive VL<200 copies/ml. Virological rebound was defined as two consecutive VL>1000 copies/ml after primary success. Predictors of success were determined using multivariate logistic regression and SAS 8.2 software. RESULTS Analysis concerned 123 patients, with 19% stage C when ARV was initiated. Their median CD4 and PVL values at baseline were 233/mm3 and 73,000 copies/ml respectively. The median duration of follow-up was of 20.7 Months [(mean (STD): 20.6 (6.7)]. Initial treatments were distributed as follows: 2 NRTI + 1NNRTI, n=66 (54%); 2 NRTI+1PI, n=44 (36%); 3 NRTI, n=13 (10%). Primary success was obtained in 100 (81,3%) patients. Among these, 6 (6%) developed secondary virologic failure. The absence of change in initial ARV treatment within first 4 Months, and good compliance to treatment were statistically associated with primary success in univariate (p values respectively: 0.004 and 0.04) and in multivariate analysis (p respectively: 0.009 and 0.03). The proportion of failure was higher in the patients with lower baseline CD4 levels lesser than 200/mm3 (p=0.09). CONCLUSIONS In this cohort of patients, tolerance and compliance to the first regimen were associated to primary success. These results emphasize the role of compliance in primary success and reinforces need to work on compliance in such patients.