The purpose of this study was to determine lymphocyte CD4 T-cell count and circulating HIV-1 RNA load in HIV-infected adults starting first line antiretroviral treatment according to the revised 2006 WHO recommendations in Cotonou, Benin. A total of 1209 adults treated mainly by lamivudine/stavudine/nevirapine, were prospectively included between November 2006 and June 2007. CD4 T-cell counts and HIV viral load (measured by branched DNA assay, Siemens, Tarytown, New York, USA) were evaluated at 6 months of treatment. Mean CD4 T-cell count showed a marked increase at six months of treatment (93/mm3 at baseline versus 387/mm3 at 6 months) with 65.2% of patients reaching a CD4 T-cell level higher than 200/mm3 and 34.8% showing CD4 T-cell counts lower than 200/mm3. At 6 months, HIV 1 viral load was undetectable (<2.70 log10 copies/ml) in only 54 patients (16.7%), detectable but lower than 3.0 log10 copies/ml in 522 (73%) patients, and high, i.e., still greater than 3.7 log10 copies/ml in 188 (27%) patients. After 18 months of follow up, 499 patients (41.3%) had undetectable circulating viral load. The three main findings of this study are that at 6 months of antiretroviral treatment i) one-third of patients remained at risk for opportunistic infection (CD4<200/mm3), ii) one-fourth met criteria for virological failure (> 5000 copies/ml), and iii) concordance between immunological and virological responses was frequent but discordance responses were observed in more than 10% of patients. Taken together, these findings underline the need to improve compliance and laboratory follow-up in patients undergoing antiretroviral therapy in Africa.