In the present study, we investigated whether a gross deletion in the nef gene ($g{Delta}nef$) is induced by Korean red ginseng (KRG) intake. Ten patients were treated with KRG powder for 3 years in the absence of antiretroviral drug therapy. On average, $3,555{pm}1,042;g$ KRG was administered per person over $36.1{pm}2.4$ months. There was a mild decrease in CD4 T cell count ($75{pm}110/{mu}L$) over the $36.1{pm}2.4$ months (p = 0.059). We obtained 355 nef amplicons using 71 peripheral blood mononuclear cell samples over a 3-year period. All ten patients exhibited g${Delta}$nef (range, 3.2 to 45.9%). At baseline, 3 of 78 amplicons (3.8%) exhibited $g{Delta}nef$, whereas 18.8% (52/277) revealed $g{Delta}nef$ during KRG-intake (p<0.001). The proportion of $g{Delta}nef$ was significantly correlated with monthly dose of KRG (r=0.89, p<0.001). The median time for first detection of $g{Delta}nef$ was 13 months. In conclusion, our data show that $g{Delta}nef$ is inducible by KRG intake and its proportion is dependent on the duration of KRG intake and dose of KRG.