This study sought to investigate the impacts of the antiretroviral (ARV) therapy regimens currently used in Chinese HIV-1-infected individuals. Seven hundred eighteen ARV-treated and treatment-naive HIV-1-infected individuals living in seven provinces were enrolled in 2005 by a multistage sampling approach according to a national cross-sectional survey program on HIV-1 drug resistance. All patients were investigated clinically, and CD4+ T cell counts and HIV-1 viral loads were measured while genotyping for drug resistance was determined by a home brew nested PCR. Viral inhibition in ARV-treated individuals was higher than that in ARV treatment-naive individuals. The overall prevalence of drug-resistant mutations was 37.8%. Higher frequencies of mutations in ARV-treated and drug withdrawal groups were found than in the ARV treatment-naive group (P<0.01). Of the four regimens currently used, the D4T/3TC/NVP regimen showed a higher-level viral inhibition. No statistical significance was found among the four regimens in drug-resistant mutations. The rate of resistance-associated mutations to non-nucleotide reverse transcriptase inhibitors (NNRTIs) was higher than that to nucleotide reverse transcriptase inhibitors (NRTIs) (P<0.01). The most common mutations conferring resistance to NNRTIs were K103N, Y181C and G190A, representing 56.5, 30.4 and 14.5%, respectively. Furthermore, higher viral inhibition and a lower rate of drug-resistant mutations were achieved in the good compliance group. This study revealed an efficient viral inhibition achieved with the current first-line regimens in China. Most of these regimens could rapidly result in emergence of drug-resistant mutations, suggesting that a second-line ARV therapy is urgently needed and that the compliance with treatment must be emphasized during long-term treatment.