Background: To date, no study has described disease progression in Asian patients infected with HIV-1 subtype D. Methods: To determine whether the disease progression differs in patients infected with subtypes D and B prior to starting combination antiretroviral therapy, the annual decline (AD) in CD4� T cell counts over 96 59 months was retrospectively analyzed in 163 patients and compared in subtypes D and B based on the nef gene. Results: CD4� T cell AD was significantly higher in the six subtype Deinfected patients than in the 157 subtype Beinfected patients irrespective of Korean Red Ginseng (KRG) treatment (p <
0.001). Of these, two subtype Deinfected patients and 116 subtype Beinfected patients had taken KRG. AD was significantly lower in patient in the KRG-treated group than in those in the KRG-na�ve group irrespective of subtype (p <
0.05). To control for the effect of KRG, patients not treated with KRG were analyzed, with AD found to be significantly greater in subtype Deinfected patients than in subtype Beinfected patients (p <
0.01). KRG treatment had a greater effect on AD in subtype Deinfected patients than in subtype B einfected patients (4.5-fold vs. 1.6-fold). Mortality rates were significantly higher in both the 45 KRGna�ve (p <
0.001) and all 163 (p <
0.01) patients infected with subtype D than subtype B. Conclusion: Subtype D infection is associated with a >
2-fold higher risk of death and a 2.9-fold greater rate of progression than subtype B, regardless of KRG treatment.