OBJECTIVE: To explore the efficacy of integrating Traditional Chinese Medicine(TCM) and anti-retroviral therapy(ART), a customized combination of different classes of medications which was also called cock-tail treatment, on the immunological nonresponse(INR) in people living with human immunodeficiency virus(HIV)(PLWH).METHODS: Relevant literature in databases such as China National Knowledge Infrastructure Database(CNKI), Wanfang Digital Journal, Chinese Medical Journal Database(CMJD), Chinese Biomedical Literature Database(CBM), Pub Med, Cochrane, and Embase was reviewed by two independent investigators. Data were extracted from the studies according to the eligible criteria and analyzed using Review Manager 5.3.RESULTS: Nine randomized controlled trials(RCTs)with 1078 patients were analyzed. Our analyses showed that CD4 T cell counts in the treatment group improved compared with that in the control group [mean difference(MD) = 13.51, 95% confidence interval(CI): 7.42-19.60, P < 0.0001]. There was no significant difference between the treated and control groups after 3 months(MD = 25.31,95% CI:-2.78 to 53.41, P = 0.08). However, after 6 and 12 months, the response of the treatment group was superior to the control group(MD =27.45, 95% CI: 7.09-47.81, P = 0.008 and MD = 27.34,95% CI: 6.31–48.37, P = 0.01, respectively). The clinical efficacy of the treatment group was also higher than that of the control group(RR = 1.75, 95% CI:1.16-2.65, P = 0.007). However, CD45 RO and CD45 RA T cell counts did not differ significantly between the two groups(MD = 12.37, 95% CI:-6.71 to 31.45, P = 0.20 and MD = 5.67, 95% CI:-3.00 to14.35, P = 0.20, respectively).CONCLUSION: The combined treatment strategy of integrated TCM and Western Medicine promotes long-term reconstitution of the immune system and thus, is beneficial and has potential use for improving INR in PLWH. However, large-scale RCTs are required to provide evidence for optimal intervention strategies.