Abstract: Objective To observe the effect of highly active antiretroviral therapy (HAART) on HIV-positive subjects with primary drug-resistant in Shanghai, and to assess the effects of the long-term HAART for the improvement of treatment strategies in the future.Methods Untreated HIV-infected individuals were randomly selected from Shanghai AIDS treatment database from 2007 to 2013. Plasma samples of selected individuals were tested for primary drug resistance. Individuals with primary drug resistance were followed up for 1 to 7 years. The treatment effect was measured by CD4+ count and viral load test.Results Of 1 543 untreated HIV-1 infected individuals, 42 (2.7%) were found to have primary drug-resistance. Among 42 cases, 8 were lost to follow-up, 1 died and 1 stopped taking medicine. Except for these 10 individuals, 32 cases were selected for our research. Non-nuclear nucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations occurred in 11 of 32 cases (34.4%), nucleoside reverse transcriptase inhibitor (NRTI) resistance mutations in 7 cases (21.9%), protease inhibitor (PI) resistance mutations in 6 cases (18.6%). There were 3 co-resistance mutations (NRTI/NNRTI). There were 3 co-resistance mutations (1 NNRTI/PI mutation, 2 NRTI/PI mutations). Integrase inhibitor (IN) resistance mutations in 2 cases (6.3%). During the follow-up of 32 HIV-positive patients, the CD4+T cell counts were 249.5157.4, 304.9188.7, 356.3206.4, 441.4245.7, 455.4256.8, 453.2168.5, 458.2202.4, 454.066.8 and 432.0100.4/l respectively before and 6 months, 1 year, 2 years, 3 years, 4 years, 5 years, 6 and 7 years (1 months) after HAART treatment. Medication adherence showed an extremely effective viral inhibition, 30 (93.8%) cases showed no detectable viral load in the plasma, except for two cases showing an imperfect viral inhibition (600 and 700 copies/ml), who exchanged the first-line or second-line therapy regimens with others.Conclusion Our study revealed that, it is no necessary to test primary drug resistance of HIV-1 for patients in the areas with low prevalence of primary drug resistance and with rigorous implement of standard antiviral treatment and better adherence of patients, who still always carry out HIV primary resistance surveillance.