Objective To observe that antiretroviral efficacy, immune reconstitution of four-year highly active antiretroviral therapy (HAART), and evaluate its side effect in Chinese HIV-1-infected patients. Methods A total of 258 HIV-1 infected patients, given HAART regimens composed of two nucleoside reverse transcriptase inhibitor (NRTI) and one non-nucleoside reverse transcriptase inhibitor (NNRTI) for mean 51.5 months, measured HIV RNA viral load(VL) and the counts of CD4+ T cell,CD8+ T cell at the baseline and 6, 12, 24, 36 and 48 months after HAART initiation, respectively,monitoring side effect, blood routine, main biochemical parameters, and other disadvantageous accidents during the 51.5-month treatment. Results Plasma HIV-1 RNA level was determined by fluorescent quantitative polymerase chain reactions (FQ-PCR) at the baseline and 6, 12, 24, 36 and 48 months after starting HAART, and showed 5.27, 2.97, 2. 74, 2. 62, 2. 67 and 2.75 lg (copies/ml), respectively. The counts of CD4+ T cell from (127±63) cells/μl at the baseline increased to (190±115), (248±93),(269±127), (296 ± 156) and (317 ± 195) cells/μl at 6, 12, 24, 36 and 48 months after starting HAART. A total of 149 treated patients (57.8%)had gastrointestinal side effects, peripheral polyneuropathy, various rashes, central nervous system disorders, fever or baldness. Twenty-two patients changed one of three medicines to another because toxicity. Sixteen changed the regimen to the second line HAART for lactic acidosis or other serious toxicities. Conclusions A total of 258 HIV-1 infected Chinese patients treated with two NRTI and one NNRTI as first line HAART regimen during mean 51.5 months,showed a good antiretroviral efficacy and immune reconstitution, but a few site-effects at the parts of patients. It is necessary to treat adverse effect and change HAART regimen for severe toxicity in time.